Organocatalytic asymmetric alkenylation of carbonyl compounds

Asymmetric alkenylation of carbonyl compounds using organocatalysed reaction with respective organoelement reagents has developed into a useful and practically important method for the synthesis of enantiomerically enriched homoallylic amines and alcohols. As Type 1 reagents, secondary allylboronates and linear γ-functionalised allyltrichlorosilanes transfer stereochemical information (chirality or E/Z configuration) into the product.

The first reaction leads to synthetically important, unprotected Z-homoallylic amines which were previously inaccessible by direct methods. These compounds can serve as useful synthetic building blocks for syntheses of alkaloids and other natural, medicinal and bioactive compounds. The second reaction is the key step in the preparation of chiral cis-vinyl epoxides, a structural motif that was employed in the total synthesis of prostaglandins and other bioactive compounds.

The first chapter of this thesis describes a novel, highly efficient kinetic resolution method of a novel class of chromatographically-stable chiral secondary crotylboronates, and their application for a practical, direct synthesis of unprotected (S,Z)-homoallylic amines. Synthesis of homoallylic amines with an internal double bond so far was hampered by the lack of efficient asymmetric synthesis of precursor boronates, which are mostly unstable during purification by chromatography or by distillation and therefore difficult to access as individual compounds.

The second part uncovers efficient activation of unreactive γ-chloroallyltrichlorosilanes by employing novel chiral bipyridine-N,N’-dioxides as chiral Lewis base catalysts and demonstrates their synthetic potential for the asymmetric synthesis of difficult-to-access chiral cis-vinylepoxides. It is important to note that direct synthesis of chiral cis-vinylepoxides is problematic due to difficulty in achieving chemoselective oxidation of the respective dienes.