Enantiodivergent Deprotonation/Acylation of α-Amino Nitriles

摘要

Although α-nitrile carbanions are outstanding nucleophiles for carbon-carbon bond formation because of their powerful nucleophilic character resulting from the small steric demand, the difficulties that have been associated with their generation in an enantioselective manner have presented serious limitations to their usage in asymmetric synthesis. A recent publication from our laboratory has shown that enantioselective in situ trapping of extremely stereolabile chiral α-oxycarbanions of acyclic nitriles is possible at a practically promising level by taking advantage of the powerful chelating ability of an O-carbamoyl group for configurational stabilization of a carbanion, where no chiral elements other than a preexisting stereogenic center are present (Scheme 1). Coldham and co-workers successfully extended this approach to magnesiated nitriles. Herein, we report an enantiodivergent trapping of a chiral α-carbanion generated from α-amino nitrile derivatives, in which the stereogenecity of a single enantiomer can be used to produce both enantiomers.