Various methodologies utilizing alkyl metal compounds or metal salts in combination with a chiral ligand are used to transform aldehydes or ketones and terminal alkynes to propargylic alcohols. Virtually none of the established transition metal-catalyzed protocols are universally applicable to aliphatic as well as aromatic aldehydes and ketones. On the other hand simple procedures utilizing cheap and easy manageable alkaline bases are comparable concerning reactivity and tolerance but afford no chiral induction.
We developed alkynylations of various aldehydes and ketones under practical phase-transfer conditions at room temperature. This straightforward methodology combines one-pot synthesis and simple workup with good to excellent yields for propargylic alcohols derived from aliphatic aldehydes and ketones. Even aromatic aldehydes and ketones could be transformed to the corresponding propargylic alcohols in slightly lower yields. As the coordination between the PT-catalyst and the in situ generated carbanion is implied in this and other PTC reactions, we also made efforts to develop stereoselective alkynylations utilizing chiral PT-catalysts.
The addition of alcohols to epoxides leads to the synthetically important class of beta-alkoxy alcohols. As alcohols behave as poor nucleophiles in such substitution reactions the methodologies applied reach from simple BrØnsted acid catalysis to SET involving redox processes. Due to the SN2-akin reaction type, only racemic mixtures can be obtained from non-enantiopure material. Chiral Lewis acids lead to desymmetrizations in case of meso-epoxides and kinetic resolutions when unsymmetric racemic epoxides are implemented. We present a mild and efficient method for the completely regioselective alcoholysis of styrene oxides utilizing a cooperative Brønsted acid type organocatalytic system comprised of equimolar amounts of mandelic acid (1 mol%) and N,N´-bis-[3,5-bis- (trifluoromethyl)phenyl]-thiourea (1 mol%). Various styrene oxides are readily transformed into their corresponding beta-alkoxy alcohols in good to excellent yields at full conversion. Simple aliphatic, sterically demanding as well as unsaturated and acid sensitive alcohols can be employed. Utilizing mandelic acid as chiral catalyst stereoselective transformations of epoxides to the corresponding ß-alkoxy alcohols are under investigation.
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