Enantioselective synthesis of boron-substituted quaternary carbon stereogenic centers through NHC-catalyzed conjugate additions of (pinacolato)boron units to enones

Abstract

The first examples of Lewis base catalyzed enantioselective boryl conjugate additions (BCAs) that generate products containing boron-substituted quaternary carbon stereogenic centers are disclosed. Reactions are performed in the presence of 1.0-5.0 mol% of a readily accessible chiral accessible N-heterocyclic carbene (NHC) and commercially available bis(pinacolato)diboron; cyclic or linear α,β-unsaturated ketones can be used and rigorous exclusion of air or moisture is not necessary. The desired products are obtained in 63-95% yield and 91:9 to >99:1 enantiomeric ratio (e.r.). The special utility of the NHC-catalyzed approach is demonstrated in the context of an enantioselective synthesis of natural product antifungal (-)-crassinervic acid.

Keywords: N-heterocyclic carbenes; boron; conjugate additions; enantioselective synthesis; organic synthesis.