Matrix Isolation of Novel Reactive Intermediates − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – __________________________________________________________________________________________________________ Inauguraldissertation zur Erlangung des Doktorgrades der naturwissenschaftlichen Fachbereiche im Fachgebiet Organische Chemie (Fachbereich 08) der Justus-Liebig-Universität Gießen vorgelegt von Bastian Bernhardt aus Langen angefertigt im Zeitraum von Oktober 2018 bis September 2021 am Institut für Organische Chemie der Justus-Liebig-Universität Gießen Betreuer: Prof. Dr. Peter R. Schreiner, PhD Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 2 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ Eidesstattliche Erklärung Hiermit versichere ich, die vorgelegte Dissertation selbständig und ohne unerlaubte fremde Hilfe und nur mit den Hilfen angefertigt zu haben, die ich in der Dissertation angegeben habe. Alle Textstellen, die wörtlich oder sinngemäß aus veröffentlichten Schriften entnommen sind, und alle Angaben, die auf mündlichen Auskünften beruhen, sind als solche kenntlich gemacht. Bei den von mir durchgeführten und in der Dissertation erwähnten Untersuchungen habe ich die Grundsätze guter wissenschaftlicher Praxis, wie sie in der „Satzung der Justus- Liebig-Universität zur Sicherung guter wissenschaftlicher Praxis“ niedergelegt sind, eingehalten. ___________________________ ___________________________ Ort, Datum Unterschrift Dekan: Prof. Dr. Thomas Wilke Prodekan: Prof. Dr. Klaus Müller-Buschbaum Studiendekan: Prof. Dr. Richard Göttlich Erstgutachter: Prof. Dr. Peter R. Schreiner, PhD Zweitgutachter: Prof. Dr. Bernd Smarsly 3 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 4 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ Zusammenfassung Kleine, reaktive Moleküle werden als Intermediate in atmosphärischen und astronomischen Prozessen postuliert, sind jedoch häufig kaum oder überhaupt nicht untersucht. Mithilfe der Matrixisolationstechnik gelingt es, die Lebensdauer solcher Spezies unter kryogenen Bedingungen zu verlängern und somit ihre Charakterisierung mit spektroskopischen Methoden zu ermöglichen. Der quantenmechanische Tunneleffekt führt dazu, dass selbst manche matrixisolierte Moleküle nicht persistent sind. Untersuchungen dieses Effekts führten schließlich zu einem neuen Prinzip in der Chemie, nämlich dem der Tunnelkontrolle. Im Rahmen dieser Arbeit wurden, unter anderem, zwei neue Hydroxycarbene dargestellt und bezüglich ihrer Tunnelreaktivität analysiert. Von besonderem Interesse ist der Einfluss des Substituenten auf die Tunnelkinetik. So soll dazu beigetragen werden, ein besseres und intuitives Verständnis chemischer Tunnelprozesse zu erlangen, damit der Effekt beispielsweise in synthetischen Aufgabenstellungen gezielt eingesetzt werden kann. Die in dieser Arbeit erstmals dargestellten Spezies wurden außerdem in der Literatur bezüglich ihrer Rolle in atmosphärischen oder astronomischen Vorgängen diskutiert. Ihre direkte spektroskopische Charakterisierung stellt die chemische Grundlage postulierter Mechanismen und Modelle solcher Prozesse dar. In der ersten Veröffentlichung wurde das bisher unbekannte Thiolimintautomer HC(NH)SH des Thioformamids (HC(S)NH2) in kryogenen Argon- und Stickstoffmatrices photochemisch generiert. Eines der beobachteten vier Konformere dieser neuen Verbindung geht eine durch Tunneln ermöglichte Torsion um die C–S Bindung ein. Die erstmalige Darstellung und spektroskopische Charakterisierung des Aminohydroxymethylens (H2N–C̈–OH) ist Gegenstand der zweiten Publikation. Aminohydroxymethylen ist in einer Argonmatrix bei 3 K persistent und zerfällt unter Bestrahlung mit UV-Licht zu NH3 + CO sowie HNCO + H2. Über ein weiteres neues Hydroxycarben, nämlich Ethynylhydroxycarben (HC≡C–C̈–OH), wird in der dritten Veröffentlichung berichtet. Dieses reagiert in einem konformerspezifischen und für Hydroxycarbene typischen Tunnelprozess zu Propinal. In der vierten Publikation wurde das bisher unbekannte cis-cis-Konformer des Dihydroxycarbens (HO–C̈–OH) durch Bestrahlung mit nahem Infrarotlicht aus energetisch niedrigeren Konformeren in einer Stickstoffmatrix erzeugt. Neben Konformerentunneln deuten die gemessenen Kinetiken des Abbaus dieser Verbindung auf eine Nebenreaktion, nämlich den Zerfall zu CO2 und H2, hin. 5 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 6 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ Abstract Small, reactive molecules are intermediates postulated in atmospheric and astrochemical processes. However, little to nothing is known about many such species. With the help of the matrix isolation technique the lifetime of reactive molecules can be increased allowing for their direct spectroscopic investigation. Quantum mechanical tunneling leads to the depletion of some matrix-isolated species. Investigating this effect eventually led to a novel chemical principle, namely tunneling control. During this work, two novel hydroxycarbenes, among others, were generated and their tunneling behaviors were studied. The focus lies on the effect of substitution on tunneling half-lives, aiming to create a better and more intuitive understanding of quantum mechanical tunneling in chemistry. This might eventually enable exploiting this effect, e.g., in chemical synthesis. The species generated herein were discussed regarding their role in atmospheric and astrochemical processes in the literature and their direct spectroscopic characterization provides the chemical basis for models used in these fields. In the first publication, the hitherto unknown thiolimine tautomer HC(NH)SH of thioformamide (HC(S)NH2) was generated photochemically in cryogenic argon and dinitrogen matrices. One of the four observed conformers of this species reacts in a tunneling-enabled C–S rotamerization. The second publication reports the first generation and spectroscopic characterization of aminohydroxymethylene (H2N–C̈–OH). Aminohydroxymethylene is persistent in solid argon at 3 K and decomposes to NH3 + CO as well as HNCO + H2 upon UV excitation. Another novel hydroxycarbene, namely ethynylhydroxycarbene (HC≡C–C̈–OH), is the subject of the third publication. The compound reacts in a conformer-specific quantum mechanical tunneling process, which is typical for hydroxycarbenes, to propynal. The fourth publication describes the formation of the hitherto unknown cis-cis-conformer of dihydroxycarbene (HO–C̈–OH) from energetically lower-lying conformers by irradiation with near-infrared light in solid dinitrogen. Besides conformational tunneling, the measured kinetic profiles of the decay of this new compound hint towards a side reaction, namely its decomposition to CO2 and H2. 7 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 8 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ Preface This thesis comprises the work conducted during my doctoral studies in the group of Prof. Dr. P. R. Schreiner. Its first chapter contains an overview of the advances in tunneling studies applied in Organic Chemistry. These mainly highlight matrix isolation experiments, but also include some references to chemistry conducted in standard wet laboratories. Starting from the physical foundation of tunneling and its first observations in chemical reactions we proceed to examples that led to what is nowadays called tunneling control. We report that tunneling is able of qualitatively influencing a reaction’s outcome, which is in contrast to the mainstream chemist’s viewpoint of only some years ago. As most examples, including our own work, are related to chemistry discussed in the context of atmospheric and astrochemical processes, we provide some background information about these issues in the beginning of Chapter 1. However, we take a rather chemical perspective and do not go into details of the more general implications of the (chemical) findings presented herein. At the end of Chapter 1, we briefly discuss our preliminary results in projects that have not been published yet. They further stress the possibilities one can realize when exploiting tunneling effects. While our own work is mentioned in the Introduction, detailed information can be obtained from the respective peer-reviewed publications, which are reproduced with permission from the publishers in Chapter 2. For experimental details we refer to the corresponding Supporting Information, which is publicly available on the publishers’ websites. This work would not have been possible if it were not for the help of many. I thank all my mentors, colleagues, and friends, who supported me during the past years. I hope that the findings presented herein will be helpful for other researchers or even inspire completely new projects. Bastian Bernhardt Gießen, 11th October 2021 9 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 10 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ Table of Contents Eidesstattliche Erklärung .................................................................................................. 3 Zusammenfassung ............................................................................................................ 5 Abstract ............................................................................................................................. 7 Preface .............................................................................................................................. 9 1. Introduction ............................................................................................................... 13 1.1 Motivation and Goals ................................................................................................ 13 1.2 Sulfur-Containing Compounds in Atmospheric and Prebiotic Chemistry ............... 14 1.3 Quantum Mechanical Tunneling in Chemistry ......................................................... 17 1.3.1 The Physical Background of Quantum Mechanical Tunneling ................. 18 1.3.2 Matrix Isolation Studies on Quantum Mechanical Tunneling ................... 19 1.3.3 Quantum Mechanical Tunneling in Reactions Conducted under Ambient Conditions ........................................................................................................... 27 1.3.4 Computational Predictions on Quantum Mechanical Tunneling ............... 28 1.4 Outlook ..................................................................................................................... 29 1.4.1 CO2 Activation with Aminomercaptocarbene ........................................... 29 1.4.2 Isotope-Controlled Selectivity by QMT .................................................... 31 1.5 Concluding Remarks ................................................................................................. 33 1.6 Bibliography ............................................................................................................. 33 2. Publications ............................................................................................................... 41 2.1 Characterization of the Simplest Thiolimine: The Higher Energy Tautomer of Thioformamide ............................................................................................................... 41 2.2 Ethynylhydroxycarbene (H–C≡C–C̈–OH) ............................................................... 51 2.3 Aminohydroxymethylene (H2N–C̈–OH), the Simplest Aminooxycarbene .............. 59 2.4 Identification and Reactivity of s-cis,s-cis-Dihydroxycarbene, a New [CH2O2] Intermediate .................................................................................................................... 67 2.5 Further co-Authored Publications ............................................................................. 73 3. Acknowledgment – Danksagung ............................................................................. 75 11 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 12 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 1. Introduction 1.1 Motivation and Goals Advances in synthetic organic chemistry during the last decades tremendously increased the pool of accessible molecules benefitting vital areas like medicinal drug design and materials research. In stark contrast, an estimate from 2012 shows that >99.9% of small molecules have never been synthesized.[1] These data refer to stable compounds, typically meaning such molecules that are persistent under ambient conditions. Taking fleeting (i.e., reactive) species such as radicals or carbenes into account, even molecules consisting of only a handful of atoms are only scarcely studied. Many of these compounds potentially play a role in astrochemistry and atmospheric chemistry. About 200 different compounds have been found in space until today;[2] some examples are depicted in Figure 1. While insights in astrochemistry provoke profound questions about the origin of life, chemical reactions in Earth’s atmosphere directly impact our climate. The latter issue is of special interest in current times of climate crisis. The conditions in outer space allow for the existence of seemingly exotic species (e.g., tricarbon monoxide[3,4] in Figure 1). Low temperatures and extremely high dilution prevent the occurrence of most intermolecular chemical reactions that would lead to their depletion. However, in denser parts of space, like molecular clouds, a manifold of reactions has been observed or proposed.[5] These often seem unfamiliar considering reactivity we know from ambient laboratory conditions. However, from a universal point of view, space is governed by the reactivity of such small molecules and our planet represents only a small – and in many regards even very special – subsystem. The assumption that a lot of knowledge in (organic) chemistry exists crumbles when thinking outside typical wet-laboratory conditions. Figure 1: Examples of molecules detected in space[3,4,6–10] showing that a variety of functional groups are present (1-3). These relate to the compounds characterized herein. More than 200 species have hitherto been identified in space.[2] During my doctoral studies, we isolated and characterized such hitherto elusive species using the matrix isolation technique in conjunction with infrared (IR) and ultraviolet/visible (UV/Vis) spectroscopy. We were especially interested in the study of quantum mechanical tunneling and photochemical reactions of such molecules. In a typical experiment, a volatile sample is evaporated together with an excess of a host gas (here argon (Ar) or dinitrogen (N2); the matrix material) onto a cold CsI (for IR) or BaF2 (for UV/Vis measurements) window (Figure 2). Reactive species can be generated in situ either by pyrolysis of the substrate prior to deposition or via photolysis directly on the cold window. The technique allows probing intramolecular reactivity of species trapped in an inert matrix, a situation resembling conditions found in interstellar ice grains. 13 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ furnace Ar supply sample cold window connector Ar cold window (CsI or BaF 2) precursor 3 K pyrolysis zone − 710 mbar (up to 1000 °C) Ar Figure 2: Top: Matrix apparatus. Bottom: Schematic representation. This thesis aims probing the tunneling reactivity of the parent thiolimine and hitherto unknown hydroxycarbenes, all of which resemble candidates of atmospherically or astronomically relevant compounds. Another goal is exploring the conformational reactivity in dihydroxycarbene. The last project raises the question of the feasibility to activate CO2 in a tunneling process. Generally, deciphering tunneling mechanisms and disentangling the various influences on this quantum effect is a key step in transferring quantum mechanical tunneling from a curiosity to a tool that can be used to control chemical reactions. 1.2 Sulfur-Containing Compounds in Atmospheric and Prebiotic Chemistry Sulfur-containing compounds affect cloud formation in Earth’s atmosphere as they form grain-like structures, which induce water condensation.[11] The main channel for the formation of such structures is the oxidation of dimethyl sulfide (4), which is released in 14 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ huge amounts by phytoplankton from the oceans into the marine boundary layer.[12,13] Among the most abundant oxidizing agents in the atmosphere are OH and NO3 radicals.[14,15] Other conceivable oxidizers, which have been widely discussed in recent years, are carbonyl oxides, also known as Criegee intermediates (12, Figure 3).[16] The simplest Criegee intermediate (R = R’ = H) was characterized in the last decade,[17,18] while its structure had already been correctly predicted in 1949.[19,20] We report a new isomer (cis-cis-dihydroxycarbene) of this intriguing species further below. A simplified overview of the mechanism of the oxidation of 4 is depicted in Figure 3.[15] Figure 3: Overview of the oxidation of 4 in the earth’s atmosphere adapted from Barnes et al.[15] Spectroscopically characterized intermediates (vide infra) are highlighted in blue. Bottom-right edge: General structure of Criegee intermediates, which may act as oxidizing agents besides OH and NO3 radicals in atmospheric processes. While the methyl sulfinyl (9),[21,22] methyl sulfonyl (10),[23] and methyl sulfonyloxyl (11)[24] radicals have been characterized by matrix isolation spectroscopy, the very first intermediate (methyl thiomethyl, 5) in Figure 3, a carbon-centered radical bearing a sulfur atom in α-position, remains elusive.[25] In our recent investigation, we could isolate a derivative of such a species (15) and subsequently investigated its intramolecular and intermolecular reactivity by doping the matrix with triplet dioxygen 3O2 (Figure 4). [26] Figure 4: Generation of an α-sulfenyl radical (15) via photochemical C–S bond cleavage in para- nitrobenzaldehyde dithiane (14).[26] Biradical 15 does not react with 3O2. Many more sulfur-containing compounds have been matrix-isolated and discussed regarding their role in atmospheric reactions (Figure 5) like, inter alia, the vinylsulfinyl radical (17),[27] alkynyl thiocyanate and isomers (18),[28] the phenylsulfinyl radical (19),[29] disulfur dioxide (20),[30] the methoxysulfinyl radical (21),[31] the sulfinyl radical 22,[32] and the hypothiocyanite radical (23).[33] While climate scientists build models to predict Earth’s climate or evaluate data for accurate weather forecasts, the underlying chemical reactions are still poorly understood and many postulated intermediates 15 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ unknown. Chemical studies as the ones listed are needed to build the chemical foundation of such models. Figure 5: Examples of matrix-isolated sulfur-containing compounds with potential relevance in atmospheric processes.[27–33] With the same motivation, we studied the photochemistry of N-sulfonylamine (24, Figure 6) in cooperation with Xiaoqing Zeng’s research group.[34] The reactivity of 24 represents another example of the rich and somewhat unfamiliar monomolecular chemistry of small molecules similar to those depicted in Figure 5. Figure 6: Species observed upon photolysis at different wavelengths of matrix-isolated 24.[34] Thioamides represent a widely abundant class of sulfur-containing compounds. They have, e.g., been used synthetically to generate biorelevant thiazoles via the reaction with aldehydes.[35] In the prebiotic context, their intermediacy in the formation of various amino acids has been implied experimentally.[36] While plenty of data exist on thioamides (30), surprisingly little is known about parent thioformamide (30a).[37] Thioformamide is a likely candidate for detection in space as it can be generated from HCN and H S,[38]2 both of which have been detected in interstellar media.[39,40] During my doctoral studies, we isolated 30a (prepared from formamide and phosphorus pentasulfide)[41] in solid Ar and N2 matrices and photochemically generated four conformers of the tautomeric thiolimine (31a), a compound which had remained elusive up to now.[42] In the course of this project, we also recorded the first X-ray diffraction data of 30a. Some thioamides and their thioamide → thiolimine tautomerizations have been investigated under matrix isolation conditions – both photochemically and in terms of quantum mechanical tunneling (QMT) by keeping the matrix in the dark for a certain period of time (Figure 7).[43–53] Only for thiourea (30c)[49,50] and dithiooxamide (30d)[45] a thiolimine → thioamide QMT reaction has been reported. The absence of such reactivity in parent 30a clearly shows that thiolimine → thioamide QMT is not the intrinsic reactivity of thioamides, but only (remote) substitution enhances this process. We discuss the effect of substitution on QMT in more detail in the next section. 16 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ Figure 7: Matrix-isolated thioamides which have been tautomerized to their corresponding thiolimine isomer.[43–53] The cases for which thiolimine → thioamide tautomerization occurs via QMT are highlighted in red. In our study, we observed a different QMT reaction, namely trans-trans-thiolimine (31a-tt) → cis-trans-thiolimine (31a-ct) with a half-life of ca. 30 min in both matrix materials (Figure 8).[42] This result is analogous to that of two studies on the methyl derivative (31b), which have been conducted simultaneously in Coimbra.[52,53] The reactions depicted in Figure 8 represent the first examples of QMT in C–SH rotations. QMT induced rotations around C–OH bonds, which are much more common, are discussed in the next section. We also showed that the analogous rotamerization is absent in the perdeuterated isotopologue, which is a clear indication for QMT. Figure 8: Conformational QMT of thiolimine tautomers of thioformamide[42] (31a-tt, left) and thioacetamide[52] (31b-tt, right). 1.3 Quantum Mechanical Tunneling in Chemistry The previous section concludes with an example illustrating the importance of quantum mechanical tunneling (QMT) in chemical reactions under cryogenic conditions. Note that these resemble the conditions encountered in space rather closely. In this section, we will briefly explain the background and physical foundations of QMT before illustrating its emergence in (organic) chemistry by discussing key examples from literature. We will mention our contributions where fit. 17 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 1.3.1 The Physical Background of Quantum Mechanical Tunneling Classically, the kinetics of chemical reactions can be described by transition state theory (TST) as developed independently by Eyring[54] as well as Evans and Polanyi[55,56] in 1935. The rate constant k of any reaction is given by equation (1) where kB is Boltzmann’s constant, T the absolute temperature, and h Planck’s constant. 𝑘 B ∙ 𝑇 𝑘 = ∙ 𝐾‡ (1) ℎ The equilibrium constant K‡ between the transition state and the reactants is given by equation (2), with the Gibbs free energy of activation ∆G‡ and the gas constant R. Typically, ∆G‡ is obtained from quantum chemical computations via partition functions. ∆𝐺‡ 𝐾‡ = exp (− ) (2) 𝑅 ∙ 𝑇 QMT is a direct consequence of the laws of quantum mechanics. While, classically, particles trapped in a potential energy well can only escape if their energy exceeds the activation barrier ∆G‡, quantum mechanics dictates that there is a probability for escape even if this criterion is not met. This can be illustrated by representing the particle with its wavefunction Ψ as in Figure 9. Figure 9: The probability for the detection of a particle on the right side of the barrier is not zero even if its energy does not exceed ∆G‡. The particle (red) is represented by the square of the absolute value of its wavefunction |Ψ|2, i.e., the probability of localizing the particle at a specific position in space. For an observer, the particle appears to tunnel through the barrier. Applying this concept on chemical reactions implies that there is a chance to observe reactivity even though there is not enough energy available for the starting material to overcome the transition state. This can be accounted for in TST by multiplying a correcting factor κ. 𝑘B ∙ 𝑇 𝑘 = 𝜅 ∙ ∙ 𝐾‡ (3) ℎ Jeffreys,[57] Wentzel,[58] Kramers,[59] and Brillouin[60] (JWKB) developed an approximate solution to the eigenproblem originating from Schrödinger’s equation[61] to calculate the probability of a random particle to tunnel through an arbitrary energy barrier. The resulting barrier penetration integral θ is given by equation (4). 18 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 𝑠2 𝜃 = ∫ √2(𝑉(𝑥) − 𝜀) 𝑑𝑥 (4) 𝑠1 In equation (4), V(x) is the energy potential, ε the collision energy (sometimes called attempt energy related to the attempt frequency ω0), and s1 and s2 two points (known as turning points) on V(x) on either side of the barrier at the energy level ε. In terms of θ, the JWKB transmission probability κJWKB is given by equation (5). 1 𝜅JWKB = (5) 1 + exp(2𝜃) The JWKB tunneling half-life τWKB can be calculated from equation (6) by using the speed of light c as a conversion factor. log (2) 𝜏JWKB = (6) 𝜔0 ∙ 𝑐 ∙ 𝜅JWKB A somewhat more instructive way to quantify QMT within the JWKB approximation for a parabolic barrier is given by equation (7). A particle’s energy-dependent JWKB tunneling probability P(E) depends linearly on the activation barrier’s width w and on the square root of its height V0 as well as the effective mass m. Hence, the impact on P(E) upon changing the barrier width is larger compared to a change in barrier height or particle mass. We will encounter this aspect in the case studies considered in the following section. −𝜋2 ∙ 𝑤 ∙ √2 ∙ 𝑚 ∙ (𝑉0 − 𝐸) 𝑃(𝐸) = exp ( ) (7) ℎ 1.3.2 Matrix Isolation Studies on Quantum Mechanical Tunneling As under matrix isolation conditions most reactions cannot be realized classically (meaning the situation is similar as in Figure 9), it is not surprising that this technique proved to be of utmost importance to directly observe QMT reactions experimentally. The second requirement to elucidate the effect of QMT is the availability of reliable computational methods to predict ∆G‡. While temperature-independent reaction rates (constant Arrhenius plots) or anomalously large kinetic isotope effects (KIE) are experimental indications for QMT, for many systems QMT rates can readily be computed.[62–64] Different software packages designed for this purpose are available.[62,65,66] Before the emergence of the studies discussed in the following, QMT has been considered, if any, only as a means of indecisive rate acceleration by most organic chemists.[67] Note that the first experimental observation of QMT in 1928 was based on the emission of He2+, a chemically relevant mass.[68] The perception of QMT as a merely quantitative (and in many cases negligible) effect on reaction rates (e.g., derived from activation barriers obtained from Arrhenius plots) only changed in the last decades, when more and more examples were reported in which QMT changes the experimental outcome in a qualitative fashion. 19 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ In 2011, our group introduced the novel concept of tunneling control, expanding the notion of thermodynamic versus kinetic control.[69–71] Matrix-isolated methylhydroxycarbene (33a) reacts to the thermodynamic product acetaldehyde (34a) instead of the kinetic product vinyl alcohol (32) at 11 K and in the absence of external stimuli (Figure 10). Only QMT explains that any reaction occurs at all, but, what is more, only tunneling control can explain the qualitative reaction outcome. Note that a similar example has already been reported in 1994 on the C–H insertion in tert- butylchlorocarbene,[72] but the concept of tunneling control had not been noticed back then. Again, the availability of high-level computational tools was key to decipher the underlying reaction mechanism: for example, in the 2011 study the focal point analysis (FPA) technique[73–77] was employed on coupled-cluster[78–82]-optimized geometries. Figure 10: QMT control in methylhydroxycarbene (33a). Relative energies in kcal mol−1 were computed at the FPA//AE-CCSD(T)/cc-pCVQZ[83,84] level of theory.[69] The notion of tunneling control as the third reactivity paradigm[70] opens the door for exploiting QMT in order to achieve a desired reaction outcome that is qualitatively different from classical expectations. In 2017, Gerbig and Schreiner showed that it is even possible to obtain a tunneling product (Figure 11),[85] which could neither have formed under thermodynamic nor kinetic control. Figure 11: Formation of a tunneling product (37) from ketene 36 generated photochemically from ortho-nitrobenzaldehyde in various matrix hosts. Relative energies in kcal mol−1 were computed at the CCSD(T)/cc-pVTZ//MP2[86]/aug-cc-pVDZ level of theory.[85] Some systems display multiple QMT-reaction channels, e.g., benzazirine 39 (Figure 12) reacts to nitrene 38 via nitrogen tunneling as well as to the cyclic ketenimine 40 via carbon tunneling.[87] A possibility of influencing the selectivity in related cases by incorporating isotope labeling of the starting material is discussed in the outlook section. 20 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ Figure 12: Competitive nitrogen and carbon tunneling in benzazirine 39.[87] The example in Figure 12 illustrates the possibility for atoms other than hydrogen to undergo QMT processes. Such reactions are summarized under the term heavy-atom tunneling.[88] It becomes feasible if the reaction barrier is very narrow, which is often the case in pericyclic reactions when trajectories are short.[89] Experimental examples of carbon tunneling include the unsubstituted benzazirine → ketene rearrangement in Figure 12[90] and Cope rearrangements in substituted semibullvalenes.[91,92] The first observed of such reactions is the automerization of cyclobutadiene (41), which was studied using deuterium isotopologues in 1983.[93,94] The first QMT reaction of a nitrene, the nitrogen analogs of carbenes,[95] has been reported in the reaction of 2-formyl phenylnitrene to the corresponding imino ketene.[96] Some pericyclic reactions displaying QMT are depicted in Figure 13, also including cases for which QMT has been predicted computationally. Figure 13: Examples of heavy-atom QMT in pericyclic reactions. The automerization in cyclobutadiene (41) was studied on deuterium isotopologues.[94] The Cope rearrangement in semibullvalene (42) was investigated using methyl derivatives.[92] The QMT reactions of [16]annulene (43),[97] pentalene (44), heptalene (45),[98] and the Bergman cyclization in 46 were predicted computationally.[99] Another feature of QMT is its conformer-specificity and, in some cases, the inapplicability of the Curtin-Hammett principle.[100–102] This has been demonstrated for the hydroxycarbenes in Figure 14, for which both conceivable conformers were matrix isolated and only the trans-conformers (33-t) undergo QMT to the corresponding aldehyde (34).[103–105] This finding implies that QMT can be selectively switched off when generating the higher-energy cis-conformer (33-c) photochemically. Only very recently, a study reported a case where QMT can be switched on by generating a higher-energy conformer (Figure 14, right).[106] Again, these findings provide tools to control QMT reactivity in a desired fashion with the potential to use QMT in reaction design. The effect 21 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ is not limited to H-tunneling, but has also been observed in heavy-atom tunneling reactions of benzazirines.[107] Figure 14: Left: Only the trans-conformers (33-t) of F3C–C̈–OH,[103] NC–C̈–OH,[104] and HC≡C–C̈–OH[105] undergo QMT to the corresponding carbonyl compound 34. Right: Switching on QMT in 48 → 49.[106] Note that 48b only exists as an intermediate and was not detected spectroscopically due to its short QMT half-life. During the last years, some other hydroxycarbenes (33) have been isolated; the general strategy is depicted in Figure 15. Most hydroxycarbenes undergo [1,2]H-tunneling to the corresponding aldehyde (34). Deuteration of the OH moiety leads to the persistence of these hydroxycarbenes. The resulting huge KIEs and high-level computed activation barriers ranging from 20 to 30 kcal mol−1, which are insurmountable at cryogenic conditions, provide compelling evidence that QMT indeed enables the observed reactions. Note that the trajectory of the [1,2]H-shift (and, therefore, the barrier width) does play a decisive role as well: a computational study on mercapto- and selenomethylene excludes QMT in these compounds as the barrier widths are increased due to the longer bond lengths in H–C̈–S–H and H–C̈–Se–H compared to those in H–C̈–O–H.[108] Figure 15: Strategy to matrix isolate hydroxycarbenes (33). Hydroxycarbenes with R = H,[109] Me,[69] Ph,[110] tBu,[111] cyclopropyl,[112] CF ,[103] CN,[104] CCH,[105] OH,[113]3 OMe,[113] and NH [114]2 are known. Only the latter three do not undergo [1,2]H-shifts to the corresponding carbonyl compound 34. Note that NC–C̈–OH and HC≡C–C̈–OH were generated from the corresponding ethyl ester yielding the free α-keto carboxylic acid (50) as intermediate in situ. Hydroxycarbenes possess a singlet ground state. This is in contrast to the prototypical triplet electron configuration of carbenes according to Hund’s rule.[115] However, electron donation from the oxygen lone-pairs adjacent to the carbene center stabilizes the singlet state. As this results in a double-occupied sp2-type (σout-type) orbital at carbon, such carbenes are nucleophilic in nature. Furthermore, the partial double bond character of the C–O bond leads to relatively high rotamerization barriers. Note that in some 22 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ bimagnetically stable carbenes like diphenylcarbene[116–118] and bis(para- methoxyphenyl)carbene[119] the singlet-triplet energy gap is so low that the spin state can be photochemically switched under matrix isolation conditions. The simplest hydroxycarbene (R = H, 33b) is a high-energy isomer of astrochemically relevant formaldehyde.[120] As we showed prior to my doctoral studies, hydroxymethylene can be envisaged as a building block in extraterrestrial sugar formation (cf. formose/Butlerow reaction[121,122]), which occurs without the need for solvent or base and is essentially barrierless.[123] The gas-phase carbonyl-ene-type reaction depicted in Figure 16 provides a rationale for the dimerization of two formaldehyde molecules: formaldehyde (34b, an electrophile) reacts with a nucleophilic carbene counterpart (33b), which can effectively be regarded as a case of Umpolung.[124] In our study, we detected C2 (51) and C3 sugars, the latter forming in a stepwise process. Figure 16: Carbonyl-ene reaction between formaldehyde (34b) and its high-energy isomer hydroxymethylene (33b).[123] This iterative gas-phase reaction might well represent an entrance channel for the formation of sugar molecules in space. Aminohydroxymethylene (33c) is an H2N–C̈–OH species which might form from HCN and H2O in space. During my doctoral studies, we isolated 33c in an Ar matrix and investigated its photoreactivity.[114] In contrast to hydroxymethylene (33b)[109] and aminomethylene (53),[125] 33c decomposes (Figure 17) and does not undergo [1,2]H- shifts to the corresponding carbonyl (55, formamide) or imine (54, formimidic acid). However, upon pyrolysis of the precursor (oxalic acid monoamide) both 54 and 55 form among several other side products. Similar to other diheteroatom-stabilized hydroxycarbenes, 33c does not undergo intramolecular QMT (Figure 18). Figure 17: Photochemistry of aminohydroxymethylene (33c)[114] compared to hydroxymethylene (33b)[109] and aminomethylene (53).[125] Another hydroxycarbene of potential astrochemical relevance is ethynylhydroxycarbene (33d). This compound has been suggested as an intermediate in the formation of small 23 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ organic molecules from carbon clusters and water.[126,127] The stoichiometric fundamental reaction is C3 + H2O → C [128–130] 3H2O. While some C3H2O isomers have been detected in space and/or under laboratory conditions, 33d has been elusive until now. Initial claims as to its preparation in 1990[128] were refuted in 1992 on the grounds of theoretical assessments[131] and by repeating and re-interpreting the experiments in 1995.[132] During my doctoral studies, we isolated 33d employing the strategy used earlier to obtain other hydroxycarbenes (Figure 15). After pyrolysis, observed trans-ethynylhydroxycarbene (33d-t) interconverts to its cis- conformer when irradiating the matrix at 436 nm. Prolonged irradiation leads to the formation of isomeric propynal. The reaction 33d-t → propynal also occurs via QMT when keeping the matrix in the dark within a half-life of ca. three days. Hence, 33d nicely fits into the series of hydroxycarbenes’ QMT half-lives (Figure 18). Figure 18: Experimental QMT half-lives (red) of [1,2]H-shifts in hydroxycarbenes.[105] Obviously, and as already noted in the case of thioamides, the (remote) substituent plays a vital role for QMT half-lives. This is most likely due to their effect on the reaction barrier’s height and width. If substitution stabilizes the carbene center, the barrier of the reaction towards the aldehyde becomes higher and, therefore, in first approximation, also slightly wider (cf. Hammond’s postulate[133]). Apparently, the best stabilization is achieved when a second electron lone pair-bearing heteroatom is attached directly to the carbene center. In these cases QMT is not observable. The longest observable QMT half- lives are obtained in captodatively (push-pull) stabilized hydroxycarbenes. Substituent effects on QMT are not always as easily explained (note, for instance, the examples of thioamides presented above). Much data are available on rotamerizations in carboxylic acids. The first of such studies dates back to the 1997 pioneering work on the photogenerated high-energy rotamer of formic acid[134] and its subsequent QMT reaction to its ground-state conformer.[135,136] Investigations on acetic[137–139] as well as propionic acid[140] and on several other examples followed thereafter, including, inter alia, α-keto carboxylic acids,[141] trifluoro-,[142] trichloro-,[143] and tribromoacetic acid,[144] propiolic 24 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ acid,[145] oxalic acid monoamide (our precursor of aminohydroxymethylene, vide supra),[146] and a domino QMT process in oxalic acid.[147] The smaller QMT half-life of the rotamerization in acetic acid compared to formic acid was explained by the facilitated energy dissipation after formation of the lower-lying rotamer due to the presence of an alkyl rotor.[137] In 2018, we performed an analogous investigation on the rotamerization in carbonic acid[148,149] and its monomethyl ester.[150] Somewhat counterintuitively, the QMT half-life in this system increases with the mass of the remote substituent. This is in contrast to the trend in formic, acetic, and propionic acid (Figure 19). Until now, there is no satisfactory rationale for this behavior as all barrier shapes are similar according to computed data. As intrinsic effects are to be ruled out, the effect of the surroundings, i.e., the matrix material’s interaction with the substrate, is likely to account for the different trends. Figure 19: Intricate conformational QMT in carbonic acid and its (trideuterated) methyl ester.[149,150] All case studies of conformational QMT discussed so far involve the generation of the higher-energy rotamer by irradiation at energies above the corresponding activation barrier. In 2003, however, for formic acid, C–O rotamerization could even be observed when irradiating at lower energies.[151] Such light-induced or “pumped” tunneling has been controversially debated ever since and could only be shown in another system in 2019 when the methyl-substituted Criegee intermediate was photochemically decomposed to OH radicals and various side products.[152,153] It is assumed that the life- time of the excited species and the time spent by a tunneling atom within the barrier region must be comparable in order to observe pumped QMT. The latter was only measured in 2020 for Rb atoms and lies in the millisecond range.[154] Before this study, it was not even clear if a single QMT process can be associated with a time at all or happens instantaneously.[155] When studying high-energy conformers, it becomes obvious that the matrix host material has a severe impact on their persistence. For example, the high-energy conformer of the hydrocarboxyl radical (HOCO) was only detected in N2 but not in Ar matrices. [156] Its QMT reaction to the low-energy conformer in Ar is too fast to be measurable. The same is true for cis-cis-dihydroxycarbene (HO–C̈–OH, vide infra). The stabilizing effect of N2 is attributed to its higher polarizability compared to Ar. A similar trend can be observed when comparing Ar with Kr matrices. As external parameters influence QMT, these provide another tool to control this effect, especially when thinking about standard wet- laboratory conditions and the variety of accessible solvents. One might also think about enhancing QMT in a catalytic manner. Just recently, the first Lewis acid catalyzed QMT reaction under matrix isolation conditions was reported.[157] Conformational equilibria can be well studied by using near-infrared (NIR) light to interconvert specific conformers into each other. This is usually achieved by excitation 25 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ of overtones or combinational bands of O–H or N–H stretching vibrations with the help of lasers. While such irradiation typically leads to rotamerizations in the proximity of the excited bond, other examples are known where the above mentioned groups serve as antennae to induce remote reactions. These include 6-methoxyindole,[158] kojic acid,[159] NH2- and OH-substituted 2-formyl-2H-azirine, [160] and 2,6-difluoro-4-hydroxy-2H- benzazirine.[161] Generally, the reactions induced by this method are very clean, i.e., the resulting IR difference spectra are relatively easy to interpret as ideally only one reaction occurs at a time. This is in contrast to UV excitation, which often leads to various side reactions due to the higher energy input into the system and the generation of electronically excited states. The main drawback is that overtones or combinational bands in the NIR region are usually small in intensity and, hence, difficult to detect. There are, however, exceptions, e.g., the first overtone of the N–H stretching vibration in the thiolimine tautomer of thioacetamide is slightly more intense than its fundamental band.[53] In some carboxylic acids rotamerization could even be induced by excitation of the second O–H overtone.[162] We applied the strategy of NIR excitation to generate the hitherto unreported cis-cis- conformer of dihydroxycarbene (33j-cc, Figure 20),[163] an underappreciated isomer of the simplest Criegee intermediate (vide supra) although it is lower in energy. Figure 20: Generation and reactivity of cis-cis-dihydroxycarbene (33j-cc).[163] Once generated, 33j-cc spontaneously interconverts to cis-trans-dihydroxycarbene (33j-ct) via QMT within a half-life of ca. 22 min in an N2 matrix. When evaluating the decay of 33j-cc and the increase of 33j-ct, both rates cannot be satisfactorily fit when using the identical mathematical model. Only when allowing for a competitive reaction, good agreement can be achieved (Figure 21). Note that the 33j-cc depletion in Ar is too fast to record its kinetics. 26 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ Figure 21: Kinetics of the IR band profile of 33j-cc and 33j-ct using models that do not (left) and do (right) account for a side reaction forming CO2 + H [163]2. Experimental values are shown in black and fit curves in red and blue, respectively. Computations suggest that the side reaction taking place is the decomposition of 33j-cc to CO2 and H2, both of which are, unfortunately, not detectable spectroscopically: the high amounts of CO2 after pyrolysis prohibit the observability of small changes in the CO2 concentration. Attempts to indirectly prove the occurrence of this reaction using the mono- and dideuterated isotopologues of 33j failed due to very low concentrations of the carbene after pyrolysis or the inability to overcome the rotamerization barrier when exciting O–D overtones. Nevertheless, our study indicates that CO2 might take part in QMT reactions. The outlook section presents ongoing work to activate CO2 in a heavy- atom QMT process using a carbene. 1.3.3 Quantum Mechanical Tunneling in Reactions Conducted under Ambient Conditions Before briefly discussing our ongoing work, it is worthwhile to have a look at QMT reactions that have been observed under ambient conditions.[164] In the following case studies, QMT usually is more concealed than under cryogenic conditions, as many activation barriers can be overcome. Hence, measuring temperature effects as well as KIEs and comparing them to computed data is crucial to determine the contribution of QMT to a reaction rate. Nowadays, sufficient studies exist to conclude that QMT is an effect that does not play a role under matrix isolation conditions exclusively. While the focus of the work conducted herein is on matrix isolation studies, it will be interesting to see which effects discussed in Section 1.3.2 reappear in future ambient-condition experiments. The [1,2]H-shift in phenylhydroxycarbene (33h, Figures 15 and 18) has been studied at temperatures between 320 and 350 K.[165] The measured k(OH)/k(OD) KIE of ca. 20 suggests that QMT still has a large contribution in this reaction even at elevated temperatures and not only under matrix isolation conditions, as discussed above. 27 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ An example of a typical laboratory reaction in which measured 13C KIEs are higher than conventional TST values (neglecting QMT) is provided by the Roush allylboration of para-anisaldehyde.[166] Only when incorporating QMT into the computations the measured rates can be fit satisfactorily. The acceleration due to QMT is a factor of 1.36 at the reaction temperature of −78 °C. The authors conclude that “heavy-atom tunneling plays a role in simple everyday organic reactions”.[166] In 2016, a study showed that a nonheme manganese(III)-peroxo complex reacts with aldehydes through hydrogen atom abstraction instead of nucleophilic addition.[167,168] Later, temperature-dependent kinetic measurements performed on the reaction of a nonheme iron(III)-hydroperoxo complex (59) with 58 concluded that QMT can dominate such hydrogen abstractions (Figure 22, left).[169] The reaction mechanism of this reaction changes from nucleophilic addition to hydrogen atom abstraction when going from higher to lower temperatures; the latter mechanism is associated with a KIE of 93 at 203 K. Note that classic k(H)/k(D) KIEs have maximum values between 6 and 8. In a related system, deuteration changes the regioselectivity of the hydrogen abstraction leading to the deformylation product 61 or carboxylic acid 62, respectively (Figure 22, right).[170] Although QMT was not discussed in the latter study, it opens the door to control reactivity in new ways by exploiting large KIEs. Figure 22: Left: The reaction mechanism depends on the temperature with the hydrogen atom abstraction being dominated by QMT at lower temperatures (TMC = 1,4,8,11-tetramethyl- 1,4,8,11-tetraazacyclotetradecane).[169] Right: Deuteration changes the reaction outcome due to an immense KIE.[170] The ligands of the manganese(III)-peroxo complex are omitted for clarity. With such intriguing results at hand, we are confident that QMT will be exploited in ambient-condition reactions in the future and are looking forward to new possibilities to manage reaction control. 1.3.4 Computational Predictions on Quantum Mechanical Tunneling As mentioned in the previous sections, the role of quantum chemical computations to detect QMT cannot be overestimated. In this section, we briefly summarize a few examples, which elucidate aspects of QMT not discussed in earlier sections. However, other studies predicting QMT have already been mentioned above. A somewhat exotic example of the possibility of fluoride tunneling in 63[171] was reported by Kozuch et al. in 2018 (Figure 23, left).[172] The effect of the linker (Y) on QMT half- lives was studied computationally. Such “ping-pong QMT” has later also been suggested for boron and carbon in similar compounds.[173] The same group also proposed carbon 28 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ QMT automerizations in specially designed fulvalenes.[174] Similarly, results were published on the automerization of the cyclopropenyl anion.[175] However, if the ring is substituted with groups other than hydrogen, QMT is inhibited due to the non-planarity of the system and the resulting long trajectories of the attached groups.[175] These studies test the limits of QMT (i.e., heavy atoms or long trajectories) and aim to establish rules of thumb for when to expect QMT. In a different vein, QMT deemed the computationally predicted record of the shortest C–C bond in a bridged tetrahedryl-tetrahedrane (64)[176] impossible to observe, because the molecule would rearrange very quickly even under cryogenic conditions via QMT (Figure 23, right).[177] The reaction is highly exergonic even though the resulting product is a carbene (65). Hence, when discussing the viability of computed minimum structures,[178] QMT has to be taken into account apart from activation barriers’ heights. Figure 23: Computationally predicted QMT reactions. Left: Ping-pong tunneling of fluoride (Y = S, SO2, Se, SeO2, SiH2, CH2, O).[172] Right: 64 is not persistent even at 0 K, because it quickly rearranges to 65 via QMT.[177] 1.4 Outlook During my doctoral studies, we worked on two more projects, which have not been published yet. Preliminary results are presented briefly in the following. 1.4.1 CO2 Activation with Aminomercaptocarbene In a hitherto unpublished cooperation with Markus Schauermann, we investigated the possibility of activating CO2 in a QMT reaction using a carbene, namely aminomercaptocarbene (67). Mercaptocarbenes are hitherto rather elusive species as only parent thiohydroxymethylene could be detected.[179] Initial attempts to generate 67 via pyrolysis of 2-amino-2-thioxoacetic acid (68) employing the standard procedure discussed in Figure 15 failed, because the reaction profiles of the decarboxylation of oxalic acid monoamide (66) and 68 are highly temperature dependent (Figure 24). While aminohydroxymethylene (33c) lies in a rather deep potential well, 67 readily undergoes a consecutive reaction to thioformamide (30a) at 1000 °C. This temperature resembles the pyrolysis conditions and we observed 30a as the main pyrolysis product in agreement with our computed data. 29 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ Figure 24: Potential energy surfaces of the decarboxylation of 66 (left) and 68 (right) at 0 K (top) and 1000 °C (bottom), respectively, computed at the B3LYP/6-311+G(3df,3pd) level of theory.[114] Therefore, we decided to perform the decarboxylation of 68 photochemically and indeed were able to generate 67 complexed with CO2 (67-CO2). Once generated, 67-CO2 reacts back to the starting material 68 at 3 K. This reaction occurs spontaneously via heavy- atom QMT when keeping the matrix in the dark as deduced from measured and computed Arrhenius plots (Figure 25). The possibility to activate CO2 and form a neutral product (and not a zwitterion) using a carbene is unprecedented. Note that the underlying mechanism is analogous to the carbonyl-ene reaction presented above (Figure 16), but uses CO2 as the carbonyl species. 30 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ T / K 20 10 7 5 4 3 25 9.6×10−12 Arrhenius behavior non-Arrhenius behavior 20 1.4×10−9 15 2.1×10−7 10 3.1×10−5 5 4.7×10−3 0 6.9×10−1 −5 1.0×102 −10 1.5×104 0.05 0.10 0.15 0.20 0.25 0.30 T-1 / K-1 Figure 25: Arrhenius plot of the 67-CO2 → 68 reaction. Red points: Experimental data. Black points: Values computed at the CVT/SCT//B3LYP/6-311+G(d,p) level of theory. The left-hand trend of the computed values agrees with classical Arrhenius behavior while the constant right- hand trend represents the QMT limit of the reaction. 1.4.2 Isotope-Controlled Selectivity by QMT As QMT is highly dependent on the mass of the atoms moving throughout the reaction, isotope-controlled selectivity by QMT seems feasible. In a computational study such cases were predicted (Figure 26).[180] However, an experimental study on this effect remains yet to be conducted. Figure 26: Isotope-controlled selectivity by QMT. The isotopologue determines whether 70 reacts to 69 or 71 as shown by computations.[180] a: R1 = OMe, R2 = H, R3 = H; b: R1 = F, R2 = H, R3 = CH3; c: R1 = F, R2 = CH3, R3 = CH3; d: R1 = F, R2 = F, R3 = H; e: R1 = F, R2 = F, R3 = F. During my research visit at the Institut Ruđer Bošković (Zagreb, Croatia), we synthesized various diazirines (74, 78, and 82) depicted in Figure 27 according to established literature procedures.[181–183] 31 ln(k) t1/2 / s Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ Figure 27: Syntheses of diazirines 74, 78, and 82. Yields of the isolated diazirines are given with respect to both steps. Carbenes 75, 79, and 83 were photochemically generated under matrix isolation conditions. In a hitherto unpublished matrix isolation study, we photochemically generated the polycyclic singlet carbenes 75 and 79 from 74 and 78, respectively. While 79 is persistent in an Ar matrix at 3 K, adamantylidene (75) tunnels to 2,4-dehydroadamantane (84) within a half-life of ca. 10 h (Figure 28). This confirms a computational prediction by Kozuch from 2014[184] and adds to an experimental study by Bally et al. from 1994.[185] Irradiating 79 at 627 nm leads to its interconversion, presumably to homopentaprismane (churchane, 85). The latter finding still needs to be verified with reference experiments. Figure 28: Experimental matrix UV/Vis spectra displaying the reactivity of 75 (left) and 79 (right). Note that the presence of 85 needs further experimental verification. Performing the analogous experiment with protoadamantane diazirine (82) does not yield the corresponding carbene 83, but rather its [1,2]H-shift product 86 (Figure 29). This is in accord with our computed half-life of only 33 ms of protoadamantylidene (83) making it unobservable even at cryogenic temperatures. We also synthesized the α,α-dideuterated isotopologue of 82. We expect a different reaction outcome for the corresponding carbene isotopologue (d2-83) as depicted in Figure 29. If this holds true, this would provide the first experimental example of isotope-controlled selectivity by QMT. 32 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ Figure 29: Isotope-controlled selectivity by QMT in protoadamantylidene (83) and its dideuterated isotopologue (d2-83). 1.5 Concluding Remarks We isolated two novel hydroxycarbenes, 33d and 33c, whose reactivity is in line with the other members of this compound class. While QMT half-lives of hydroxycarbenes can be rationalized on the basis of the electronic properties of the substituent, this is not as easily conceived for other reactions like thiolimine → thioamide tunneling or rotamerizations in carboxylic acids. In the latter case, external effects, like the matrix material, presumably play a decisive role, which we just begin to comprehend. Future work should focus on disentangling intrinsic and external influences on QMT. This might enable controlling QMT via external parameters and, eventually, introducing a new technique to manage reaction control even under standard laboratory conditions. Figure 30: Overview of novel compounds generated in this work. The four species displayed in Figure 30 potentially play a role in astrochemical or atmospheric processes. For instance, thioformamide and its thiolimine tautomer 31a are viable interstellar compounds and cis-cis-dihydroxycarbene (33j-cc), an isomer of the simplest Criegee intermediate, is a likely active species in the reaction of CO2 with H2 towards formic acid. The latter example hints towards the possibility of CO2 to participate in QMT processes. Activating CO2 in a heavy-atom QMT reaction as presented in Section 1.4.1. provides a new means for this high-interest endeavor. Generally, QMT is an abundant phenomenon in chemical reactions and we are looking forward to future studies proceeding from observing to controlling and using this intriguing quantum effect. 1.6 Bibliography [1] Reymond, J. L.; Awale, M. Exploring chemical space for drug discovery using the chemical universe database. ACS Chem. Neurosci. 2012, 3, 649–657. [2] Woon, D. E. Interstellar and circumstellar molecules. 2021, http://www.astrochymist.org/ astrochymist_ism.html [3] Matthews, H. E.; Irvine, W. M.; Friberg, P.; Brown, R. D.; Godfrey, P. D. A new interstellar molecule: 33 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ tricarbon monoxide. Nature 1984, 310, 125–126. [4] Brown, R. D.; Godfrey, P. D.; Cragg, D. M.; Rice, E. H. N.; Irvine, W. M.; Friberg, P.; Suzuki, H.; Ohishi, M.; Kaifu, N.; Morimoto, M. Tricarbon monoxide in TMC-1. Astrophys. J. 1985, 297, 302–308. [5] Herbst, E. Chemistry in the interstellar medium. Annu. Rev. Phys. Chem. 1995, 46, 27–53. [6] Feuchtgruber, H.; Helmich, F. P.; van Dishoeck, E. F.; Wright, C. M. Detection of intersteller CH3. Astrophys. J. 2000, 535, 111–114. [7] Irvine, W. M.; Brown, R. D.; Cragg, D. M.; Friberg, P.; Godfrey, P. D.; Kaifu, N.; Matthews, H. E.; Ohishi, M.; Suzuki, H.; Takeo, H. A new interstellar polyatomic molecule: detection of propynal in the cold cloud TMC-1. Astrophys. J. 1988, 335, 89–93. [8] Halfen, D. T.; Ziurys, L. M.; Brünken, S.; Gottlieb, C. A.; McCarthy, M. C.; Thaddeus, P. Detection of a new interstellar molecule: thiocyanic acid HSCN. Astrophys. J. 2009, 702, 124–127. [9] Cernicharo, J.; Cabezas, C.; Endo, Y.; Agúndez, M.; Tercero, B.; Pardo, J. R.; Marcelino, N.; de Vicente, P. The sulphur saga in TMC-1: discovery of HCSCN and HCSCCH. Astron. Astrophys. 2021, 650, 10–17. [10] Rivilla, V. M.; Jiménez-Serra, I.; Martín-Pintado, J.; Briones, C.; Rodríguez-Almeida, L. F.; Rico-Villas, F.; Tercero, B.; Zeng, S.; Colzi, L.; de Vicente, P.; Martín, S.; Requena-Torres, M. A. Discovery in space of ethanolamine, the simplest phospholipid head group. Proc. Natl. Acad. Sci. USA 2021, 118, 1–8. [11] Wang, S.; Maltrud, M.; Elliott, S.; Cameron-Smith, P.; Jonko, A. Influence of dimethyl sulfide on the carbon cycle and biological production. Biogeochemistry 2018, 138, 49–68. [12] Bates, T. S.; Lamb, B. K.; Guenther, A.; Dignon, J.; Stoiber, R. E. Sulfur emissions to the atmosphere from natural sources. J. Atmos. Chem. 1992, 14, 315–337. [13] Tyndall, G. S.; Ravishankara, A. R. Atmospheric oxidation of reduced sulfur species. Int. J. Chem. Kinet. 1991, 23, 483–527. [14] Stephens, E. R. Chemistry of atmospheric oxidants. J. Air Pollut. Control Assoc. 1969, 19, 181–185. [15] Barnes, I.; Hjorth, J.; Mihalapoulos, N. Dimethyl sulfide and dimethyl sulfoxide and their oxidation in the atmosphere. Chem. Rev. 2006, 106, 940–975. [16] Heard, D. The X factor. Nature 2012, 488, 164–165. [17] Su, Y.-T.; Lin, H. Y.; Putikam, R.; Matsui, H.; Lin, M. C.; Lee, Y. P. Extremely rapid self-reaction of the simplest Criegee intermediate CH2OO and its implications in atmospheric chemistry. Nat. Chem. 2014, 6, 477–483. [18] Lee, Y. P. Perspective: Spectroscopy and kinetics of small gaseous Criegee intermediates. J. Chem. Phys. 2015, 143, 1–16. [19] Criegee, R.; Wenner, G. Die Ozonisierung des 9,10‐Oktalins. Liebigs Ann. Chem. 1949, 564, 9–15. [20] Criegee, R. Mechanismus der Ozonolyse. Angew. Chem. 1975, 87, 765–771. [21] Reisenauer, H. P.; Romański, J.; Mlostoń, G.; Schreiner, P. R. Matrix isolation and spectroscopic properties of the methylsulfinyl radical CH •3(O)S . Chem. Commun. 2013, 49, 9467–9469. [22] Reisenauer, H. P.; Romański, J.; Mlostoń, G.; Schreiner, P. R. Reactions of the methylsulfinyl radical [CH (O)S•3 ] with oxygen (3O2) in solid argon. Chem. Commun. 2015, 51, 10022–10025. [23] Reisenauer, H. P.; Schreiner, P. R.; Romański, J.; Mlostoń, G. Gas-phase generation and matrix isolation of the methylsulfonyl radical CH3SO •2 from allylmethylsulfone. J. Phys. Chem. A 2015, 119, 2211–2216. [24] Zhu, B.; Zeng, X.; Beckers, H.; Francisco, J. S.; Willner, H. The methylsulfonyloxyl radical, CH3SO3. Angew. Chem. Int. Ed. 2015, 54, 11404–11408. [25] Mardyukov, A.; Schreiner, P. R. Atmospherically relevant radicals derived from the oxidation of dimethyl sulfide. Acc. Chem. Res. 2018, 51, 475–483. [26] Gerbig, D.; Bernhardt, B.; Wende, R. C.; Schreiner, P. R. Capture and reactivity of an elusive carbon−sulfur centered biradical. J. Phys. Chem. A 2020, 124, 2014–2018. [27] Wu, Z.; Wang, L.; Lu, B.; Eckhardt, A. K.; Schreiner, P. R.; Zeng, X. Spectroscopic characterization and photochemistry of the vinylsulfinyl radical. Phys. Chem. Chem. Phys. 2021, 23, 16307–16315. [28] Lu, B.; Wu, Z.; Wang, L.; Zhu, B.; Rauhut, G.; Zeng, X. The simplest alkynyl thiocyanate HCCSCN and its isomers. Chem. Commun. 2021, 57, 3343–3346. [29] Xu, J.; Wu, Z.; Wan, H.; Deng, G.; Lu, B.; Eckhardt, A. K.; Schreiner, P. R.; Trabelsi, T.; Francisco, J. S.; Zeng, X. Phenylsulfinyl radical: gas-phase generation, photoisomerization, and oxidation. J. Am. Chem. Soc. 2018, 140, 9972–9978. [30] Wu, Z.; Wan, H.; Xu, J.; Lu, B.; Lu, Y.; Eckhardt, A. K.; Schreiner, P. R.; Xie, C.; Guo, H.; Zeng, X. The near-UV absorber OSSO and its isomers. Chem. Commun. 2018, 54, 4517–4520. [31] Liu, Q.; Wu, Z.; Xu, J.; Lu, Y.; Li, H.; Zeng, X. Methoxysulfinyl radical CH3OSO: gas-phase generation, photochemistry, and oxidation. J. Phys. Chem. A 2017, 121, 3818–3825. [32] Wu, Z.; Liu, Q.; Xu, J.; Sun, H.; Li, D.; Song, C.; Andrada, D. M.; Frenking, G.; Trabelsi, T.; Francisco, J. S.; Zeng, X. Heterocumulene sulfinyl radical OCNSO. Angew. Chem. Int. Ed. 2017, 56, 2140–2144. [33] Wu, Z.; Xu, J.; Liu, Q.; Dong, X.; Li, D.; Holzmann, N.; Frenking, G.; Trabelsi, T.; Francisco, J. S.; Zeng, X. The hypothiocyanite radical OSCN and its isomers. Phys. Chem. Chem. Phys. 2017, 19, 16713–16720. [34] Chen, C.; Wang, L.; Zhao, X.; Wu, Z.; Bernhardt, B.; Eckhardt, A. K.; Schreiner, P. R.; Zeng, X. Photochemistry of HNSO2 in cryogenic matrices: spectroscopic identification of the intermediates and mechanism. Phys. Chem. Chem. Phys. 2020, 22, 7975–7983. [35] Ganapathi, K.; Venkataramen, A. Chemistry of thiazoles. Proc. Indian Acad. Sci. Sect. A 1945, 22, 362–378. [36] Patel, B. H.; Percivalle, C.; Ritson, D. J.; Duffy, C. D.; Sutherland, J. D. Common origins of RNA, protein and lipid precursors in a cyanosulfidic protometabolism. Nat. Chem. 2015, 7, 301–307. [37] Murai, T. Chemistry of Thioamides. 2019, Springer. 34 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ [38] Tull, R.; Weinstock, L. M. A new synthesis of thioformamide. Angew. Chem. Int. Ed. 1969, 8, 278–279. [39] Snyder, L. E.; Buhl, D. Observation of radio emission from interstellar hydrogen cyanide. Astrophys. J. 1971, 163, 47–52. [40] Thaddeus, P.; Kutner, M. L.; Penzias, A. A.; Wilson, R. W.; Jefferts, K. B. Interstellar hydrogen sulfide. Astrophys. J. 1972, 176, 73–76. [41] Willstätter, R.; Wirth, T. Über Thioformamid. Ber. Dtsch. Chem. Ges. 1909, 42, 1908–1922. [42] Bernhardt, B.; Dressler, F.; Eckhardt, A. K.; Becker, J.; Schreiner, P. R. Characterization of the simplest thiolimine: the higher energy tautomer of thioformamide. Chem. Eur. J. 2021, 27, 6732–6739. [43] Nowak, M. J.; Lapinski, L.; Rostkowska, H.; Leś, A.; Adamowicz, L. Theoretical and matrix-isolation experimental study on 2(1H )-pyridinethione/2-pyridinethiol. J. Phys. Chem. 1990, 94, 7406–7414. [44] Nowak, M. J.; Lapinski, L.; Fulara, J.; Leś, A.; Adamowicz, L. Theoretical and infrared matrix isolation study of 4(3H)-pyrimidinethione and 3(2H)-pyridazinethione. Tautomerism and phototautomerism. J. Phys. Chem. 1991, 95, 2404–2411. [45] Lapinski, L.; Rostkowska, H.; Khvorostov, A.; Yaman, M.; Fausto, R.; Nowak, M. J. Double-proton-transfer processes in dithiooxamide: UV-induced dithione → dithiol reaction and ground-state dithiol → dithione tunneling. J. Phys. Chem. A 2004, 108, 5551–5558. [46] Prusinowska, D.; Lapinski, L.; Nowak, M. J.; Adamowicz, L. Tautomerism, phototautomerism and infrared spectra of matrix-isolated 2-quinolinethione. Spectrochim. Acta Part A Mol. Spectrosc. 1995, 51, 1809–1826. [47] Brás, E. M.; Fausto, R. An insight into methimazole phototautomerism: central role of the thiyl radical and effect of benzo substitution. J. Mol. Struct. 2018, 1172, 42–54. [48] Brás, E. M.; Fausto, R. Controlled light-driven switching in 2-thiobenzimidazole. J. Photochem. Photobiol. A Chem. 2018, 357, 185–192. [49] Rostkowska, H.; Lapinski, L.; Khvorostov, A.; Nowak, M. J. Proton-transfer processes in thiourea: UV induced thione → thiol reaction and ground state thiol → thione tunneling. J. Phys. Chem. A 2003, 107, 6373– 6380. [50] Rostkowska, H.; Lapinski, L.; Nowak, M. J. Hydrogen-atom tunneling through a very high barrier; spontaneous thiol → thione conversion in thiourea isolated in low-temperature Ar, Ne, H2 and D2 matrices. Phys. Chem. Chem. Phys. 2018, 20, 13994–14002. [51] Lapinski, L.; Rostkowska, H.; Khvorostov, A.; Nowak, M. J. UV induced proton transfer in thioacetamide: first observation of thiol form of simple thioamide. Phys. Chem. Chem. Phys. 2003, 5, 1524–1529. [52] Góbi, S.; Nunes, C. M.; Reva, I.; Tarczay, G.; Fausto, R. S–H rotamerization via tunneling in a thiol form of thioacetamide. Phys. Chem. Chem. Phys. 2019, 21, 17063–17071. [53] Góbi, S.; Reva, I.; Csonka, I. P.; Nunes, C. M.; Tarczay, G.; Fausto, R. Selective conformational control by excitation of NH imino vibrational antennas. Phys. Chem. Chem. Phys. 2019, 21, 24935–24949. [54] Eyring, H. The activated complex and the absolute rate of chemical reactions. Chem. Rev. 1935, 17, 65–77. [55] Evans, M. G.; Polanyi, M. Some applications of the transition state method to the calculation of reaction velocities, especially in solution. Trans. Faraday Soc. 1935, 31, 875–894. [56] Evans, M. G.; Polanyi, M. Inertia and driving rorce of chemical reactions. Trans. Faraday Soc. 1938, 34, 11– 24. [57] Jeffreys, H. On certain approximate solutions of linear differential equations of the second order. Proc. London Math. Soc. 1924, 23, 428–436. [58] Wentzel, G. Über strahlungslose Quantensprünge. Z. Phys. 1927, 43, 524–530. [59] Kramers, H. A. Wellenmechanik und halbzahlige Quantisierung. Z. Phys. 1926, 39, 828–840. [60] Brillouin, L. Remarques sur la mécanique ondulatoire. J. Phys. le Radium 1926, 7, 353–368. [61] Schrödinger, E. Quantisierung als Eigenwertproblem. Ann. Phys. 1926, 80, 437–590. [62] Kästner, J. Theory and simulation of atom tunneling in chemical reactions. Wires. Comput. Mol. Sci. 2014, 4, 158–168. [63] Meisner, J.; Kästner, J. Atom tunneling in chemistry. Angew. Chem. Int. Ed. 2016, 55, 5400–5413. [64] Borden, W. T. Reactions that involve tunneling by carbon and the role that calculations have played in their study. Wires. Comput. Mol. Sci. 2016, 6, 20–46. [65] Isaacson, A. D.; Truhlar, D. G.; Rai, S. N.; Steckler, R.; Hancock, G. C.; Garrett, B. C.; Redmon, M. J. POLYRATE: a general computer program for variational transition state theory and semiclassical tunneling calculations of chemical reaction rates. Comput. Phys. Commun. 1987, 47, 91–102. [66] Quanz, H.; Schreiner, P. R. TUNNEX: an easy-to-use Wentzel-Kramers-Brillouin (WKB) implementation to compute tunneling half-lives. J. Comput. Chem. 2019, 40, 543–547. [67] Ley, D.; Gerbig, D.; Schreiner, P. R. Tunnelling control of chemical reactions – the organic chemist’s perspective. Org. Biomol. Chem. 2012, 10, 3769–3956. [68] Gamow, G. The quantum theory of nuclear disintegration. Nature 1928, 122, 805–806. [69] Schreiner, P. R.; Reisenauer, H. P.; Ley, D.; Gerbig, D.; Wu, C.-H.; Allen, W. D. Methylhydroxycarbene: tunneling control of a chemical reaction. Science 2011, 332, 1300–1303. [70] Schreiner, P. R. Tunneling control of chemical reactions: the third reactivity paradigm. J. Am. Chem. Soc. 2017, 139, 15276–15283. [71] Schreiner, P. R. Quantum mechanical tunneling is essential to understanding chemical reactivity. Trends Chem. 2020, 2, 980–989. [72] Zuev, P. S.; Sheridan, R. S. Tunneling in the C−H insertion of a singlet carbene: tert-butylchlorocarbene. J. Am. Chem. Soc. 1994, 116, 4123–4124. [73] East, A. L. L.; Allen, W. D. The heat of formation of NCO. J. Chem. Phys. 1993, 99, 4638–4650. 35 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ [74] Schuurman, M. S.; Muir, S. R.; Allen, W. D.; Schaefer III, H. F. Toward subchemical accuracy in computational thermochemistry: focal point analysis of the heat of formation of NCO and [H,N,C,O] isomers. J. Chem. Phys. 2004, 120, 11586–11599. [75] Bartlett, M. A.; Liang, T.; Pu, L.; Schaefer III, H. F.; Allen, W. D. The multichannel n-propyl + O2 reaction surface: definitive theory on a model hydrocarbon oxidation mechanism. J. Chem. Phys. 2018, 148, 1–18. [76] Császár, A. G.; Allen, W. D.; Schaefer III, H. F. In pursuit of the ab initio limit for conformational energy prototypes. J. Chem. Phys. 1998, 108, 9751–9764. [77] Gonzales, J. M.; Allen, W. D.; Schaefer III, H. F. Model identity SN2 reactions CH −3X + X (X = F, Cl, CN, OH, SH, NH2, PH2): Marcus Theory analyzed. J. Phys. Chem. A 2005, 109, 10613–10628. [78] Stanton, J. F. Why CCSD(T) works: a different perspective. Chem. Phys. Lett. 1997, 281, 130–134. [79] Čížek, J. On the correlation problem in atomic and molecular systems. Calculation of wavefunction components in Ursell‐type expansion using quantum‐field theoretical methods. J. Chem. Phys. 1966, 45, 4256–4266. [80] Purvis, G. D.; Bartlett, R. J. A full coupled‐cluster singles and doubles model: the inclusion of disconnected triples. J. Chem. Phys. 1982, 76, 1910–1918. [81] Raghavachari, K.; Trucks, G. W.; Pople, J. A.; Head-Gordon, M. A fifth-order perturbation comparison of electron correlation theories. Chem. Phys. Lett. 1989, 157, 479–483. [82] Crawford, T. D.; Schaefer III, H. F. An introduction to coupled cluster theory for computational chemists. Rev. Comput. Chem. 2000, 14, 33–136. [83] Dunning, T. H. Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen. J. Chem. Phys. 1989, 90, 1007–1023. [84] Woon, D. E.; Dunning, T. H. Gaussian basis sets for use in correlated molecular calculations. V. Core‐valence basis sets for boron through neon. J. Chem. Phys. 1995, 103, 4572–4585. [85] Gerbig, D.; Schreiner, P. R. Formation of a tunneling product in the photorearrangement of o- nitrobenzaldehyde. Angew. Chem. Int. Ed. 2017, 56, 9445–9448. [86] Møller, C.; Plesset, M. S. Note on an approximation treatment for many-electron systems. Phys. Rev. 1934, 46, 618–622. [87] Nunes, C. M.; Eckhardt, A. K.; Reva, I.; Fausto, R.; Schreiner, P. R. Competitive nitrogen versus carbon tunneling. J. Am. Chem. Soc. 2019, 141, 14340–14348. [88] Castro, C.; Karney, W. L. Heavy‐atom tunneling in organic reactions. Angew. Chem. Int. Ed. 2020, 132, 8355– 8366. [89] Doubleday, C.; Armas, R.; Walker, D.; Cosgriff, C. V.; Greer, E. M. Heavy-atom tunneling calculations in thirteen organic reactions: tunneling contributions are substantial, and Bell’s formula closely approximates multidimensional tunneling at ≥250 K. Angew. Chem. Int. Ed. 2017, 56, 13099–13102. [90] Inui, H.; Sawada, K.; Oishi, S.; Ushida, K.; McMahon, R. J. Aryl nitrene rearrangements: spectroscopic observation of a benzazirine and its ring expansion to a ketenimine by heavy-atom tunneling. J. Am. Chem. Soc. 2013, 135, 10246–10249. [91] Schleif, T.; Mieres-Perez, J.; Henkel, S.; Ertelt, M.; Borden, W. T.; Sander, W. The Cope rearrangement of 1,5-dimethylsemibullvalene-2(4)-d1: experimental evidence for heavy-atom tunneling. Angew. Chem. Int. Ed. 2017, 56, 10746–10749. [92] Schleif, T.; Tatchen, J.; Rowen, J. F.; Beyer, F.; Sanchez-Garcia, E.; Sander, W. Heavy-atom tunneling in semibullvalenes: how driving force, substituents, and environment influence the tunneling rates. Chem. Eur. J. 2020, 26, 10452–10458. [93] Whitman, D. W.; Carpenter, B. K. Limits on the activation parameters for automerization of cyclobutadiene- 1,2-d2. J. Am. Chem. Soc. 1982, 104, 6473–6474. [94] Carpenter, B. K. Heavy-atom tunneling as the dominant pathway in a solution-phase reaction? Bond shift in antiaromatic annulenes. J. Am. Chem. Soc. 1983, 105, 1700–1701. [95] Wentrup, C. Carbenes and nitrenes: recent developments in fundamental chemistry. Angew. Chem. Int. Ed. 2018, 57, 11508–11521. [96] Nunes, C. M.; Knezz, S. N.; Reva, I.; Fausto, R.; McMahon, R. J. Evidence of a nitrene tunneling reaction: spontaneous rearrangement of 2-formyl phenylnitrene to an imino ketene in low-temperature matrixes. J. Am. Chem. Soc. 2016, 138, 15287–15290. [97] Michel, C. S.; Lampkin, P. P.; Shezaf, J. Z.; Moll, J. F.; Castro, C.; Karney, W. L. Tunneling by 16 carbons: planar bond shifting in [16]annulene. J. Am. Chem. Soc. 2019, 141, 5286–5293. [98] Kozuch, S. Heavy atom tunneling in the automerization of pentalene and other antiaromatic systems. RSC Adv. 2014, 4, 21650–21656. [99] Greer, E. M.; Cosgriff, C. V.; Doubleday, C. Computational evidence for heavy-atom tunneling in the Bergman cyclization of a 10-membered-ring enediyne. J. Am. Chem. Soc. 2013, 135, 10194–10197. [100] Curtin, D. Y. Stereochemical control of organic reactions differences in behaviour of diastereoisomers. Rec. Chem. Prog. 1954, 15, 111–128. [101] Seeman, J. I. Effect of conformational change on reactivity in organic chemistry. Evaluation, applications, and extensions of Curtin-Hammett/Winstein-Holness kinetics. Chem. Rev. 1983, 83, 84–134. [102] Seeman, J. I. The Curtin-Hammett principle and the Winstein-Holness equation: new definition and recent extensions to classical concepts. J. Chem. Educ. 1986, 63, 42–48. [103] Mardyukov, A.; Quanz, H.; Schreiner, P. R. Conformer-specific hydrogen atom tunnelling in trifluoromethylhydroxycarbene. Nat. Chem. 2017, 9, 71–76. [104] Eckhardt, A. K.; Erb, F. R.; Schreiner, P. R. Conformer-specific [1,2]H-tunnelling in captodatively-stabilized 36 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ cyanohydroxycarbene (NC–C̈–OH). Chem. Sci. 2019, 10, 802–808. [105] Bernhardt, B.; Ruth, M.; Eckhardt, A. K.; Schreiner, P. R. Ethynylhydroxycarbene (H–C≡C–C̈–OH). J. Am. Chem. Soc. 2021, 143, 3741–3746. [106] Roque, J. P. L.; Nunes, C. M.; Viegas, L. P.; Pereira, N. A. M.; Pinho, T. M. V. D.; Schreiner, P. R.; Fausto, R. Switching on H‑tunneling through conformational control. J. Am. Chem. Soc. 2021, 143, 8266–8271. [107] Schleif, T.; Mieres-Perez, J.; Henkel, S.; Mendez-Vega, E.; Inui, H.; McMahon, R. J.; Sander, W. Conformer- specific heavy-atom tunneling in the rearrangement of benzazirines to ketenimines. J. Org. Chem. 2019, 84, 16013–16018. [108] Sarka, J.; Császár, A. G.; Schreiner, P. R. Do the mercaptocarbene (H–C–S–H) and selenocarbene (H–C–Se– H) congeners of hydroxycarbene (H–C–O–H) undergo 1,2-H-tunneling? Collect. Czechoslov. Chem. Commun. 2011, 76, 645–667. [109] Schreiner, P. R.; Reisenauer, H. P.; Pickard IV, F. C.; Simmonett, A. C.; Allen, W. D.; Mátyus, E.; Császár, A. G. Capture of hydroxymethylene and its fast disappearance through tunnelling. Nature 2008, 453, 906– 909. [110] Gerbig, D.; Reisenauer, H. P.; Wu, C.; Ley, D.; Allen, W. D.; Schreiner, P. R. Phenylhydroxycarbene. J. Am. Chem. Soc. 2010, 132, 7273–7275. [111] Ley, D.; Gerbig, D.; Schreiner, P. R. Tunneling control of chemical reactions: C–H insertion versus H- tunneling in tert-butylhydroxycarbene. Chem. Sci. 2013, 4, 677–684. [112] Ley, D.; Gerbig, D.; Wagner, J. P.; Reisenauer, H. P.; Schreiner, P. R. Cyclopropylhydroxycarbene. J. Am. Chem. Soc. 2011, 133, 13614–13621. [113] Schreiner, P. R.; Reisenauer, H. P. Spectroscopic identification of dihydroxycarbene. Angew. Chem. Int. Ed. 2008, 47, 7071–7074. [114] Bernhardt, B.; Ruth, M.; Reisenauer, H. P.; Schreiner, P. R. Aminohydroxymethylene (H2N–C̈–OH), the simplest aminooxycarbene. J. Phys. Chem. A 2021, 125, 7023–7028. [115] Hund, F. Zur Deutung der Molekelspektren. I. Zeitschrift für Phys. 1927, 40, 742–764. [116] Costa, P.; Sander, W. Hydrogen bonding switches the spin state of diphenylcarbene from triplet to singlet. Angew. Chem. Int. Ed. 2014, 53, 5122–5125. [117] Costa, P.; Fernandez-Oliva, M.; Sanchez-Garcia, E.; Sander, W. The highly reactive benzhydryl cation isolated and stabilized in water ice. J. Am. Chem. Soc. 2014, 136, 15625–15630. [118] Knorr, J.; Sokkar, P.; Schott, S.; Costa, P.; Thiel, W.; Sander, W.; Sanchez-Garcia, E.; Nuernberger, P. Competitive solvent-molecule interactions govern primary processes of diphenylcarbene in solvent mixtures. Nat. Commun. 2016, 7, 1–8. [119] Costa, P.; Lohmiller, T.; Trosien, I.; Savitsky, A.; Lubitz, W.; Fernandez-Oliva, M.; Sanchez-Garcia, E.; Sander, W. Light and temperature control of the spin state of bis(p-methoxyphenyl)carbene: a magnetically bistable carbene. J. Am. Chem. Soc. 2016, 138, 1622–1629. [120] Snyder, L. E.; Buhl, D.; Zuckerman, B.; Palmer, P. Microwave detection of interstellar formaldehyde. Phys. Rev. Lett. 1969, 22, 679–681. [121] Butlerow, A. Bildung einer zuckerartigen Substanz durch Synthese. Justus Liebigs Ann. Chem. 1861, 120, 295–298. [122] Breslow, R. On the mechanism of the formose reaction. Tetrahedron Lett. 1959, 1, 22–26. [123] Eckhardt, A. K.; Linden, M. M.; Wende, R. C.; Bernhardt, B.; Schreiner, P. R. Gas-phase sugar formation using hydroxymethylene as the reactive formaldehyde isomer. Nat. Chem. 2018, 10, 1141–1147. [124] Seebach, D. Methods of reactivity Umpolung. Angew. Chem. Int. Ed. 1979, 18, 239–258. [125] Eckhardt, A. K.; Schreiner, P. R. Spectroscopic evidence for aminomethylene (H−C̈−NH2)—the simplest amino carbene. Angew. Chem. Int. Ed. 2018, 57, 5248–5252. [126] Ekern, S.; Szczepanski, J.; Vala, M. An ab initio study of the C3H2O potential surface: a mechanism for propynal formation and destruction. J. Phys. Chem. 1996, 100, 16109–16115. [127] Ekern, S.; Vala, M. Theoretical study of photochemical mechanisms of C3O formation. J. Phys. Chem. A 1997, 101, 3601–3606. [128] Ortman, B. J.; Hauge, R. H.; Margrave, J. L.; Kafafi, Z. H. Reactions of small carbon clusters with water in cryogenic matrices. The FTIR spectrum of hydroxyethynylcarbene. J. Phys. Chem. 1990, 94, 7973–7977. [129] Dibben, M.; Szczepanski, J.; Wehlburg, C.; Vala, M. Complexes of linear carbon clusters with water. J. Phys. Chem. A 2000, 104, 3584–3592. [130] Schreiner, P. R.; Reisenauer, H. P. The “non-reaction” of ground-state triplet carbon atoms with water revisited. Chem. Phys. Chem. 2006, 7, 880–885. [131] Liu, R.; Zhou, X.; Pulay, P. Ab initio study of the identity of the reaction product between C3 and water in cryogenic matrices. J. Phys. Chem. 1992, 96, 5748–5752. [132] Szczepanski, J.; Ekern, S.; Vala, M. Spectroscopy and photochemistry of the C3·H2O complex in argon matrices. J. Phys. Chem. 1995, 99, 8002–8012. [133] Hammond, G. S. A correlation of reaction rates. J. Am. Chem. Soc. 1955, 77, 334–338. [134] Pettersson, M.; Lundell, J.; Khriachtchev, L.; Räsänen, M. IR spectrum of the other rotamer of formic acid, cis-HCOOH. J. Am. Chem. Soc. 1997, 119, 11715–11716. [135] Pettersson, M.; Maçôas, E. M. S.; Khriachtchev, L.; Lundell, J.; Fausto, R.; Räsänen, M. Cis→trans conversion of formic acid by dissipative tunneling in solid rare gases: influence of environment on the tunneling rate. J. Chem. Phys. 2002, 117, 9095–9098. [136] Khriachtchev, L.; Pettersson, M.; Räsänen, M. Conformational memory in photodissociation of formic acid. J. Am. Chem. Soc. 2002, 124, 10994–10995. 37 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ [137] Maçôas, E. M. S.; Khriachtchev, L.; Pettersson, M.; Fausto, R.; Räsänen, M. Rotational isomerism in acetic acid: the first experimental observation of the high-energy conformer. J. Am. Chem. Soc. 2003, 125, 16188– 16189. [138] Maçôas, E. M. S.; Khriachtchev, L.; Fausto, R.; Räsänen, M. Photochemistry and vibrational spectroscopy of the trans and cis conformers of acetic acid in solid Ar. J. Phys. Chem. A 2004, 108, 3380–3389. [139] Maçôas, E. M. S.; Khriachtchev, L.; Pettersson, M.; Fausto, R.; Räsänen, M. Rotational isomerism of acetic acid isolated in rare-gas matrices: effect of medium and isotopic substitution on IR-induced isomerization quantum yield and cis → trans tunneling rate. J. Chem. Phys. 2004, 121, 1331–1338. [140] Maçôas, E. M. S. S.; Khriachtchev, L.; Pettersson, M.; Fausto, R.; Räsänen, M. Internal rotation in propionic acid: near-infrared-induced isomerization in solid argon. J. Phys. Chem. A 2005, 109, 3617–3625. [141] Gerbig, D.; Schreiner, P. R. Hydrogen-tunneling in biologically relevant small molecules: the rotamerizations of α-ketocarboxylic acids. J. Phys. Chem. B 2015, 119, 693–703. [142] Apóstolo, R. F. G.; Bazsó, G.; Bento, R. R. F.; Tarczay, G.; Fausto, R. The first experimental observation of the higher-energy trans conformer of trifluoroacetic acid. J. Mol. Struct. 2016, 1125, 288–295. [143] Apóstolo, R. F. G.; Bento, R. R. F.; Fausto, R. Narrowband NIR-induced in situ generation of the high-energy trans conformer of trichloroacetic acid isolated in solid nitrogen and its spontaneous decay by tunneling to the low-energy cis conformer. Croat. Chem. Acta 2015, 88, 377–386. [144] Apóstolo, R. F. G.; Bazsó, G.; Ogruc-Ildiz, G.; Tarczay, G.; Fausto, R. Near-infrared in situ generation of the higher-energy trans conformer of tribromoacetic acid: observation of a large-scale matrix-site changing mediated by conformational conversion. J. Chem. Phys. 2018, 148, 1–12. [145] Lopes, S.; Nikitin, T.; Fausto, R. Propiolic acid in solid nitrogen: NIR- and UV-induced cis → trans isomerization and matrix-site-dependent trans → cis tunneling. J. Phys. Chem. A 2019, 123, 1581–1593. [146] Maier, G.; Endres, J.; Reisenauer, H. P. Interconversions between oxalic acid monoamide rotamers: photochemical process versus tunneling. J. Mol. Struct. 2012, 1025, 2–5. [147] Schreiner, P. R.; Wagner, J. P.; Reisenauer, H. P.; Gerbig, D.; Ley, D.; Sarka, J.; Császár, A. G.; Vaughn, A.; Allen, W. D. Domino tunneling. J. Am. Chem. Soc. 2015, 137, 7828–7834. [148] Reisenauer, H. P.; Wagner, J. P.; Schreiner, P. R. Gas-phase preparation of carbonic acid and its monomethyl ester. Angew. Chem. Int. Ed. 2014, 53, 11766–11771. [149] Wagner, J. P.; Reisenauer, H. P.; Hirvonen, V.; Wu, C.-H.; Tyberg, J. L.; Allen, W. D.; Schreiner, P. R. Tunnelling in carbonic acid. Chem. Commun. 2016, 52, 7858–7861. [150] Linden, M. M.; Wagner, J. P.; Bernhardt, B.; Bartlett, M. A.; Allen, W. D.; Schreiner, P. R. Intricate conformational tunneling in carbonic acid monomethyl ester. J. Phys. Chem. Lett. 2018, 9, 1663–1667. [151] Pettersson, M.; Maçôas, E. M. S.; Khriachtchev, L.; Fausto, R.; Räsänen, M. Conformational isomerization of formic acid by vibrational excitation at energies below the torsional barrier. J. Am. Chem. Soc. 2003, 125, 4058–4059. [152] Liu, F.; Beames, J. M.; Petit, A. S.; McCoy, A. B.; Lester, M. I. Infrared-driven unimolecular reaction of CH3CHOO Criegee intermediates to OH radical products. Science 2014, 345, 1596–1598. [153] Barber, V. P.; Pandit, S.; Esposito, V. J.; McCoy, A. B.; Lester, M. I. CH stretch activation of CH3CHOO: deep tunneling to hydroxyl radical products. J. Phys. Chem. A 2019, 123, 2559–2569. [154] Ramos, R.; Spierings, D.; Racicot, I.; Steinberg, A. M. Measurement of the time spent by a tunnelling atom within the barrier region. Nature 2020, 583, 529–532. [155] Sainadh, U. S.; Xu, H.; Wang, X.; Atia-Tul-Noor, A.; Wallace, W. C.; Douguet, N.; Bray, A.; Ivanov, I.; Bartschat, K.; Kheifets, A.; Sang, R. T.; Litvinyuk, I. V. Attosecond angular streaking and tunnelling time in atomic hydrogen. Nature 2019, 568, 75–77. [156] Ryazantsev, S. V.; Feldman, V. I.; Khriachtchev, L. Conformational switching of HOCO radical: selective vibrational excitation and hydrogen-atom tunneling. J. Am. Chem. Soc. 2017, 139, 9551–9557. [157] Henkel, S.; Merini, M. P.; Mendez-Vega, E.; Sander, W. Lewis acid catalyzed heavy atom tunneling – the case of 1H-bicyclo[3.1.0]-hexa-3,5-dien-2-one. Chem. Sci. 2021, 12, 11013–11019. [158] Lopes Jesus, A. J.; Reva, I.; Araujo-Andrade, C.; Fausto, R. Conformational switching by vibrational excitation of a remote NH bond. J. Am. Chem. Soc. 2015, 137, 14240–14243. [159] Halasa, A.; Reva, I.; Lapinski, L.; Rostkowska, H.; Fausto, R.; Nowak, M. J. Conformers of kojic acid and their near-IR-induced conversions: long-range intramolecular vibrational energy transfer. J. Phys. Chem. A 2016, 120, 2647–2656. [160] Lopes Jesus, A. J.; Nunes, C. M.; Fausto, R.; Reva, I. Conformational control over an aldehyde fragment by selective vibrational excitation of interchangeable remote antennas. Chem. Commun. 2018, 54, 4778–4781. [161] Nunes, C. M.; Pereira, N. A. M.; Viegas, L. P.; Pinho e Melo, T. M. V. D.; Fausto, R. Inducing molecular reactions by selective vibrational excitation of a remote antenna with near-infrared light. Chem. Commun. 2021, 57, 9570–9573. [162] Nunes, C. M.; Reva, I.; Fausto, R. Conformational isomerizations triggered by vibrational excitation of second stretching overtones. Phys. Chem. Chem. Phys. 2019, 21, 24993–25001. [163] Quanz, H.; Bernhardt, B.; Erb, F. R.; Bartlett, M. A.; Allen, W. D.; Schreiner, P. R. Identification and reactivity of s-cis,s-cis-dihydroxycarbene, a new [CH2O2] intermediate. J. Am. Chem. Soc. 2020, 142, 19457–19461. [164] Greer, E. M.; Kwon, K.; Greer, A.; Doubleday, C. Thermally activated tunneling in organic reactions. Tetrahedron 2016, 72, 7357–7373. [165] Schäfer, M.; Peckelsen, K.; Paul, M.; Martens, J.; Oomens, J.; Berden, G.; Berkessel, A.; Meijer, A. J. H. M. Hydrogen tunneling above room temperature evidenced by infrared ion spectroscopy. J. Am. Chem. Soc. 2017, 139, 5779–5786. 38 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ [166] Vetticatt, M. J.; Singleton, D. A. Isotope effects and heavy-atom tunneling in the Roush allylboration of aldehydes. Org. Lett. 2012, 14, 2370–2373. [167] Barman, P.; Upadhyay, P.; Faponle, A. S.; Kumar, J.; Nag, S. S.; Kumar, D.; Sastri, C. V.; de Visser, S. P. Deformylation reaction by a nonheme manganese(III)–peroxo complex via initial hydrogen-atom abstraction. Angew. Chem. Int. Ed. 2016, 55, 11091–11095. [168] Cantú Reinhard, F. G.; Barman, P.; Mukherjee, G.; Kumar, J.; Kumar, D.; Kumar, D.; Sastri, C. V.; de Visser, S. P. Keto-enol tautomerization triggers an electrophilic aldehyde deformylation reaction by a nonheme manganese(III)-peroxo complex. J. Am. Chem. Soc. 2017, 139, 18328–18338. [169] Bae, S. H.; Li, X.; Seo, M. S.; Lee, Y.; Fukuzumi, S.; Nam, W. Tunneling controls the reaction pathway in the deformylation of aldehydes by a nonheme iron(III)-hydroperoxo complex: hydrogen atom abstraction versus nucleophilic addition. J. Am. Chem. Soc. 2019, 141, 7675–7679. [170] Barman, P.; Cantú Reinhard, F. G.; Bagha, U. K.; Kumar, D.; Sastri, C.; de Visser, S. P. Hydrogen by deuterium substitution in an aldehyde tunes the regioselectivity by a nonheme manganese(III)-peroxo complex. Angew. Chem. Int. Ed. 2019, 1–6. [171] Scheiner, S. Highly selective halide receptors based on chalcogen, pnicogen, and tetrel bonds. Chem. Eur. J. 2016, 22, 18850–18858. [172] Kozuch, S.; Nandi, A.; Sucher, A. Ping-pong tunneling reactions: can fluoride jump at absolute zero? Chem. Eur. J. 2018, 24, 16348–16355. [173] Nandi, A.; Sucher, A.; Tyomkin, A.; Kozuch, S. Ping-pong tunneling reactions, part 2: boron and carbon bell- clapper rearrangement. Pure Appl. Chem. 2020, 92, 39–47. [174] Solel, E.; Kozuch, S. Tuning the spin, aromaticity and quantum tunneling in computationally designed fulvalenes. J. Org. Chem. 2018, 83, 10826–10834. [175] Kozuch, S. Cyclopropenyl anions: carbon tunneling or diradical formation? A contest between Jahn-Teller and Hund. J. Chem. Theory Comput. 2015, 11, 3089–3095. [176] Martínez-Guajardo, G.; Donald, K. J.; Wittmaack, B. K.; Vazquez, M. A.; Merino, G. Shorter still: compressing C−C single bonds. Org. Lett. 2010, 12, 4058–4061. [177] Kozuch, S. A quantum mechanical “jack in the box”: rapid rearrangement of a tetrahedryl-tetrahedrane via heavy atom tunneling. Org. Lett. 2014, 16, 4102–4105. [178] Hoffmann, R.; Schleyer, P. v. R.; Schaefer III, H. F. Predicting molecules−more realism, please! Angew. Chem. Int. Ed. 2008, 47, 7164–7167. [179] Doddipatla, S.; He, C.; Kaiser, R. I.; Luo, Y.; Sun, R.; Galimova, G. R.; Mebel, A. M.; Millar, T. J. A chemical dynamics study on the gas phase formation of thioformaldehyde (H2CS) and its thiohydroxycarbene isomer (HCSH). Proc. Natl. Acad. Sci. USA 2020, 117, 22712–22719. [180] Nandi, A.; Gerbig, D.; Schreiner, P. R.; Borden, W. T.; Kozuch, S. Isotope-controlled selectivity by quantum tunneling: hydrogen migration versus ring expansion in cyclopropylmethylcarbenes. J. Am. Chem. Soc. 2017, 139, 9097–9099. [181] Isaev, S. D.; Yurchenko, A. G.; Stepanov, F. N.; Kolyada, G. G.; Novikov, S. S.; Karpenko, N. F. Synthesis and chemical reactions of adamantane-2-spiro-3’-diazirine. Zh. Org. Khim. 1973, 9, 724–727. [182] Marchand, A. P.; Kumar, K. A.; Mlinarić-Majerski, K.; Veljković, J. Intermolecular vs. intramolecular carbene reactions of a cage-functionalized cyclopentylcarbene. Tetrahedron 1998, 54, 15105–15112. [183] Šumanovac, T.; Alešković, M.; Šekutor, M.; Matković, M.; Baron, T.; Mlinarić-Majerski, K.; Bohne, C.; Basarić, N. Photoelimination of nitrogen from adamantane and pentacycloundecane (PCU) diazirines: spectroscopic study and supramolecular control. Photochem. Photobiol. Sci. 2019, 18, 1806–1822. [184] Kozuch, S. The reactivity game: theoretical predictions for heavy atom tunneling in adamantyl and related carbenes. Phys. Chem. Chem. Phys. 2014, 16, 7718–7727. [185] Bally, T.; Matzinger, S.; Truttmann, L.; Platz, M. S.; Morgan, S. Matrix spectroscopy of 2‐adamantylidene, a dialkylcarbene with singlet ground state. Angew. Chem. Int. Ed. 1994, 33, 1964–1966. 39 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 40 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 2. Publications 2.1 Characterization of the Simplest Thiolimine: The Higher Energy Tautomer of Thioformamide Abstract: As sulfur containing organic molecules thioamides and their isomers are conceivable intermediates in prebiotic chemistry, e. g., in the formation of amino acids and thiazoles and resemble viable candidates for detection in interstellar media. Here we report the characterization of parent thioformamide in the solid state via single crystal X-ray diffraction and its photochemical interconversion to its hitherto unreported higher energy tautomer thiolimine in inert argon and dinitrogen matrices. Upon photogeneration, four conformers of thiolimine form, whose ratio depends on the employed wavelength. One of these conformers interconverts due to quantum mechanical tunneling with a half-life of 30–45 min in both matrix materials at 3 and 20 K. A spontaneous reverse reaction from thiolimine to thioformamide is not observed. To support our experimental findings, we explored the potential energy surface of the system at the AE-CCSD(T)/aug-cc-pCVTZ level of theory and computed tunneling half-lives with the CVT/SCT approach applying DFT methods. Reference: Bastian Bernhardt, Friedemann Dressler, André K. Eckhardt, Jonathan Becker, and Peter R. Schreiner Chem. Eur. J. 2021, 27, 6732–6739. (DOI: 10.1002/chem.202005188) Reproduced with permission from: © 2021, John Wiley & Sons, Inc. 111 River Street Hoboken, NJ, 07030-5774 United States of America 41 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 42 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 43 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 44 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 45 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 46 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 47 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 48 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 49 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 50 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 2.2 Ethynylhydroxycarbene (H–C≡C–C̈–OH) Abstract: The species on the C3H2O potential energy surface have long been known to play a vital role in extraterrestrial chemistry. Here we report on the hitherto uncharacterized isomer ethynylhydroxycarbene (H–C≡C–C̈–OH, 1) generated by high-vacuum flash pyrolysis of ethynylglyoxylic acid ethyl ester and trapped in solid argon matrices at 3 and 20 K. Upon irradiation at 436 nm trans-1 rearranges to its higher lying cis-conformer. Prolonged irradiation leads to the formation of propynal. When the matrix is kept in the dark, 1 reacts within a half-life of ca. 70 h to propynal in a conformer-specific [1,2]H-tunneling process. Our results are fully consistent with computations at the CCSD(T)/cc-pVTZ and the B3LYP/def2-QZVPP levels of theory. Reference: Bastian Bernhardt, Marcel Ruth, André K. Eckhardt, and Peter R. Schreiner, J. Am. Chem. Soc. 2021, 143, 3741–3746. (DOI: 10.1021/jacs.1c00897) Highlight: Ethynylhydroxycarbene—A New C3H2O Species, Chemistry Views 2021. (https://www.chemistryviews.org/details/news/11292097/EthynylhydroxycarbeneA_Ne w_C3H2O_Species.html) Reproduced with permission from: © 2021, American Chemical Society 1155 16th Street NW Washington, DC, 20036 United States of America 51 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 52 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 53 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 54 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 55 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 56 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 57 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 58 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 2.3 Aminohydroxymethylene (H2N–C̈–OH), the Simplest Aminooxycarbene Abstract: We generated and isolated hitherto unreported aminohydroxymethylene (1, aminohydroxycarbene) in solid Ar via pyrolysis of oxalic acid monoamide (2). Astrochemically relevant carbene 1 is persistent under cryogenic conditions and only decomposes to HNCO + H2 and NH3 + CO upon irradiation of the matrix at 254 nm. This photoreactivity is contrary to other hydroxycarbenes and aminomethylene, which undergo [1,2]H shifts to the corresponding carbonyls or imine. The experimental data are well supported by the results of CCSD(T)/cc-pVTZ and B3LYP/6-311++G(3df,3pd) computations. Reference: Bastian Bernhardt, Marcel Ruth, Hans Peter Reisenauer, and Peter R. Schreiner J. Phys. Chem. A 2021, 125, 7023–7028. (DOI: 10.1021/acs.jpca.1c06151) Underline denotes shared first authors. Highlight: Aminohydroxymethylene, Chemistry Views 2021. (https://www.chemistryviews.org/details/news/11313638/Aminohydroxymethylene. html) Reproduced with permission from: © 2021, American Chemical Society 1155 16th Street NW Washington, DC, 20036 United States of America 59 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 60 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 61 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 62 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 63 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 64 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 65 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 66 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 2.4 Identification and Reactivity of s-cis,s-cis-Dihydroxycarbene, a New [CH2O2] Intermediate Abstract: We report the first preparation of the s-cis,s-cis conformer of dihydroxycarbene (1cc) by means of pyrolysis of oxalic acid, isolation of the lower-energy s-trans,s-trans (1tt) and s-cis,s-trans (1ct) product conformers at cryogenic temperatures in a N2 matrix, and subsequent narrow-band near-infrared (NIR) laser excitation to give 1cc. Carbene 1cc converts quickly to 1ct via quantum-mechanical tunneling with an effective half-life of 22 min at 3 K. The potential energy surface features around 1 were pinpointed by convergent focal point analysis targeting the AE-CCSDT(Q)/CBS level of electronic structure theory. Computations of the tunneling kinetics confirm the time scale of the 1cc → 1ct rotamerization and suggest that direct 1cc → H2 + CO2 decomposition may also be a minor pathway. The intriguing latter possibility cannot be confirmed spectroscopically, but hints of it may be present in the measured kinetic profiles. Reference: Henrik Quanz, Bastian Bernhardt, Frederik R. Erb, Marcus A. Bartlett, Wesley D. Allen, and Peter R. Schreiner J. Am. Chem. Soc. 2020, 142, 19457–19461. (DOI: 10.1021/jacs.0c09317) Underline denotes shared first authors. Highlight: Spotlights on Recent JACS Publications: Attabey R. Benítez J. Am. Chem. Soc. 2020, 142, 20913-20914. (DOI: 10.1021/jacs.0c12720) Reproduced with permission from: © 2020, American Chemical Society 1155 16th Street NW Washington, DC, 20036 United States of America 67 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 68 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 69 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 70 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 71 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 72 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 2.5 Further co-Authored Publications Intricate Conformational Tunneling in Carbonic Acid Monomethyl Ester. Michael M. Linden, J. Philipp Wagner, Bastian Bernhardt, Marcus A. Bartlett, Wesley D. Allen, and Peter R. Schreiner J. Phys. Chem. Lett. 2018, 9, 1663–1667. (DOI: 10.1021/acs.jpclett.8b00295) Gas-phase sugar formation using hydroxymethylene as the reactive formaldehyde isomer. André K. Eckhardt, Michael M. Linden, Raffael C. Wende, Bastian Bernhardt, and Peter R. Schreiner Nat. Chem. 2018, 10, 1141–1147. (DOI: 10.1038/s41557-018-0128-2) Highlights: a) Super-reactive molecule could solve space sugar mystery, Chemistry World 2018, (https://www.chemistryworld.com/news/super-reactive-molecule-could- solve-space-sugar-mystery/3009487.article); b) Süßes Leben – einfachste Zucker ohne Biosynthese, JLU news release 2018, (https://www.uni-giessen.de/ueber- uns/pressestelle/pm/pm158-18); c) Einfachste Zucker ohne Biosynthese – LABO Online 2018, (https://www.labo.de/news/einfachste-zucker-ohne-biosynthese.htm); d) Süßes Leben – einfachste Zucker ohne Biosynthese – Innovations Report 2018, (https://www.innovations-report.de/fachgebiete/biowissenschaften-chemie/suesses- leben-einfachste-zucker-ohne-biosynthese/). Photochemistry of HNSO2 in cryogenic matrices: spectroscopic identification of the intermediates and mechanism. Changyun Chen, Lina Wang, Xiaofang Zhao, Zhuang Wu, Bastian Bernhardt, André K. Eckhardt, Peter R. Schreiner, and Xiaoqing Zeng Phys. Chem. Chem. Phys. 2020, 22, 7975–7983. (DOI: 10.1039/D0CP00962H) Capture and Reactivity of an Elusive Carbon–Sulfur Centered Biradical. Dennis Gerbig, Bastian Bernhardt, Raffael C. Wende, and Peter R. Schreiner J. Phys. Chem. A 2020, 124, 2014–2018. (DOI: 10.1021/acs.jpca.9b11795) Underline denotes shared first authors. 73 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ 74 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 3. Acknowledgment – Danksagung Diese Arbeit wäre ohne die Hilfe zahlreicher Personen nicht zustande gekommen. Gerade in Pandemiezeiten (Computer- und Coronavirus) war und ist diese Unterstützung nicht nur aus wissenschaftlicher Hinsicht von unschätzbarem Wert. Herzlich bedanken möchte ich mich bei: Prof. Dr. Peter. R. Schreiner, PhD für die Aufnahme in seine Arbeitsgruppe, gute Ratschläge, die Freiheit in meiner Forschung und sein Vertrauen und das Fördern meiner Fähigkeiten. Prof. Dr. Bernd Smarsly für die Übernahme des Zweitgutachtens dieser Arbeit. Prof. Dr. Wesley D. Allen und seinen Mitarbeiter/innen für ihre Gastfreundschaft während meines Auslandsaufenthalts an der University of Georgia und die erfolgreiche Zusammenarbeit am Dihydroxycarben-Paper. Henrik Quanz für die sehr gute Betreuung meiner Master-Thesis und seine ständige Unterstützung in computerchemischen Fragestellungen. Markus Schauermann für die gute Zusammenarbeit im Aminomercaptocarben-Projekt. Marcel Ruth für seinen unermüdlichen Einsatz im Rahmen seiner Vertiefungs- und Spezialisierungsmodule und die erfolgreiche und gute Zusammenarbeit beim Schreiben zweier Publikationen. Friedemann Dressler, Frederik R. Erb, Finn M. Wilming und Gina M. Würl für die erfolgreiche und zuverlässige Durchführung einiger Synthesen von Matrixvorläuferverbindungen. Meinen Kollegen aus Labor B201 Finn M. Wilming, Lars Rummel und Henrik F. König für die hervorragende Arbeitsatmosphäre und zahlreiche Gespräche über Wissenschaft und mehr. Jeder von ihnen hätte 25.000 Punkte mehr als verdient. Dr. André K. Eckhardt für zahlreiche gute Ratschläge und seine externe Unterstützung in einigen Projekten. Dr. Dennis Gerbig für seine Unterstützung in wissenschaftlichen Fragestellungen und die kompetente Einführung in die Kunst der Matrixisolation während meines Studiums. Dr. Artur Mardyukov für fachliche Unterstützung sowie einige abendliche Poker- und Schachpartien. Dr. Hans Peter Reisenauer für seine hilfreichen Ratschläge bezüglich IR-Spektroskopie und die gute Zusammenarbeit im Aminohydroxycarben-Projekt. Ephrath Solel, PhD für die Durchführung einiger computerchemischer Rechnungen im Aminomercaptocarben-Projekt. Benjamin Zonker, Jama Ariai und Dr. Sascha H. Combe für die gute Arbeitsatmosphäre im Liebig-Office. Prof. Dr. Xiaoqing Zeng und seinen Mitarbeiter/innen für die gute Zusammenarbeit in einem erfolgreichen Kooperationsprojekt. 75 Matrix Isolation of Novel Reactive Intermediates _____________________________________________________________________________________ Dr. Marina Šekutor, Dr. Marija Alešković, und Dr. Nikola Basarić für ihre Gastfreundschaft während meines Forschungsaufenthalts am Institut Ruđer Bošković in Zagreb. Dr. Fumito Saito für synthetische Ratschläge. Cláudio M. Nunes, PhD für einige fruchtbare Diskussionen über tunneleffektgesteuerte Reaktionen. Jan M. Schümann und Felix Keul für Abwechslung im Doktorandenalltag. Dr. Michael M. Linden für seine exzellente Betreuung meiner Bachelor-Thesis zu Beginn meiner Zeit in der PRS Group. Dr. J. Philipp Wagner für seine Unterstützung während meiner Zeit in Athens, Georgia. Dr. Jonathan Becker für die Analyse einiger Einkristalle. Dr. Heike Hausmann für die Messung einiger NMR-Proben. Dr. Raffael C. Wende für die Messung einiger massenspektrometrischer Proben. Edgar Reitz für seine kompetente Unterstützung in technischen Fragestellungen und die Eindämmung des Computervirus. Der gesamten PRS Group für die gute Arbeitsatmosphäre. Den anderen Arbeitsgruppen des Instituts für Organische Chemie für das Bereitstellen einiger Materialien, insbesondere LED Lampen, und das stets freundliche Arbeitsumfeld. Michaela Richter und Dr. Jörg Neudert für ihre Unterstützung in administrativen Angelegenheiten. Meinen Kommilitonen und insbesondere Ruben Maile, Finn M. Wilming, David S. Kröck, Jaqueline Beppler und Tabea Köhler für die schöne und angenehme Zeit während meines Studiums. Dem Fonds der Chemischen Industrie für die finanzielle Unterstützung in Form eines Kekulé Stipendiums während meiner Promotion. Der Sektion Gießen-Oberhessen des Deutschen Alpenvereins e.V. und allen meinen Freunden für mein Leben abseits der Universität. 76 − Quantum Mechanical Tunneling in Atmospherically and Astrochemically Relevant Compounds – _____________________________________________________________________________________ 77