Reductive Umpolung Reactions

Chiral a-heteroatom-substituted carbanions are attractive C(sp³) nucleophiles for the organic synthesis of chiral molecules. Specifically, a-alkoxyalkyl anions are highly valuable in constructing chiral alcohols found in a majority of pharmaceutical drugs and bioactive natural products. Conventionally, chiral a-alkoxyalkyl anions are presynthesized as stoichiometric organometallic reagents. We reported reductive umpolung using a copper catalyst and a silylboronate to convert an aldehyde to a nucleophilic a-silyloxyalkylcopper(I) species. Thus, a chiral a-silyloxyalkylcopper(I) species can be formed catalytically from aromatic aldehydes via the enantioselective addition of a chiral N-heterocyclic carbene (NHC)-ligated silylcopper(I) complex followed by [1,2]-Brook rearrangement and subsequently coupled with various carbon electrophiles in a stereospecific manner to afford a series of chiral alcohol derivatives that are difficult to synthesize by classical methods using aldehydes as electrophiles.