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Auflistung Dissertationen/Habilitationen nach Titel "(Un)expected extensions of the multicatalysis concept"

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    (Un)expected extensions of the multicatalysis concept
    (2016) Schuler, Sören Manuel Michael
    The aim of this thesis was the establishment of an enantioselective epoxidation in the context of our multicatalysis approach in combination with the already utilized acylation and/or oxidation. As starting point we designed a new sequence consisting of acylation, epoxidation, and epoxide opening (Chapter 3.1.). After epoxidation of the unsaturated side chain the cyclohexanediol moiety should coordinate the nucleophile and enable a selective epoxide opening. After hydrolysis of the auxiliary a carboxylic acid with two stereogenic centers will be yielded.Considering the already optimized and established enantioselective acylation allyl acetate was tested as further acyl source (Chapter 2.1.). Furthermore, based on phenazine 7 we examined a possible oxidative esterification (Chapter 2.2.) and with sulfoximines 8 we wanted to extent the substrate scope (Chapter 2.3.). But, all three attempts did not show the desired result.For examination of the single steps of the new multicatalytic sequence we synthesized the racemic products of acylation (Chapter 3.2.) and epoxidation (Chapter 3.3.). Due to synthetic reasons we selected pentenoic acid derivatives as unsaturated components. Promisingly, we were able to obtain the products of trans-3-pentenoic acid after both kinetic resolution as well as desymmetrization with the corresponding cyclohexanediol with high selectivities utilizing the Steglich procedure. As alternative to the epoxidation of the crotonic acid monoesters 17 and 18 we tested the Michael addition successfully as potential second step (Chapter 3.4.1.). Both carbon nucleophiles as well as a thiol were used for the possible epoxide opening reaction starting with monoesters 24a and 25a. But, independently from the chosen conditions we obtained alpha,beta-unsaturated and gamma-hydroxylated esters 31 and 32. Either protection of the free hydroxyl group or the usage of 4-pentenoic acid led to the desired epoxide opening (Chapter 3.4.2.). After optimization using only DBU as base nearly 90% yield could be achieved for 31 and 32. Therefore, this step should be included in the multicatalytic sequence enabling a variety of possible transformations based on olefin or alcohol subsequently (Chapter 3.4.3. and 3.4.4.).For identification and optimization of a feasible epoxidation procedure a substrate library of 14 epoxides was established (Chapter 4.1.1.), because using alkenes 24 and 25 might yield enantiomers as well as diastereomers. A diacid- (Chapter 4.3.), a TFMK- (Chapter 4.4.), a PTC- (Chapter 4.5.), and a prolinol-based epoxidation approach (Chapter 4.6.) were investigated. Both catalyst synthesis and development of well-working and optimized epoxidation protocols were possible for all four concepts. Generation of an enantiomeric excess was only observable in case of prolinol-based system 192. Especially, the synthesis of a selective TFMK-derived catalyst was studied very intensively and finally several potential strategies for the synthesis of a directly functionalized amino acid were illustrated (Chapter 4.4.8 and 4.4.9.).Besides epoxidation dioxirane- (Chapter 5.3.3.) and peracid-based systems (Chapter 5.3.4.) were also tested successfully in the oxidation of sulfides. Starting materials reacted chemoselectively, but not stereoselectively to the corresponding sulfoxides in the presence of both types of catalyst. Simultaneously, a PTC- (Chapter 5.3.5.) and thiourea-based procedure (Chapter 5.3.5.4.) were also studied and an optimized protocol was established for the latter one in regard to further experiments.During dealing with the main topic of this thesis the formation of spiro carbonate 75 (Chapter 4.2.) and alpha-keto acetal 162a (Chapter 4.4.9.3.) were observed. For spiro carbonate 75 reaction conditions were optimized starting from carbamate 52c to obtain the desired product with a yield of 78%. We assume that a cooperative catalysis based on in situ generated mCBA and TCU 77 takes place. For alpha-keto acetal 162b we were able to develop an asymmetric access based on literature research and mechanistic considerations. After investigation of the existence of closed form 163 of carboxybenzaldehyde 146 in solution via IR and NMR an alkaloid-based procedure was studied. With only a few experiments we found a strategy yielding acylated derivative 162b with nearly quantitative yield and an enantiomeric excess of up to 32%. Both projects have a huge potency to be investigated in more detail.