Scalable organocatalytic asymmetric Strecker reactions catalysed by a chiral cyanide generator

Abstract

The Strecker synthesis is one of the most facile methods to access racemic α-amino acids. However, feasible catalytic asymmetric Strecker reactions for the large-scale production of enantioenriched α-amino acids are rare. Here we report a scalable catalytic asymmetric Strecker reaction that uses an accessible chiral variant of oligoethylene glycol as the catalyst and KCN to generate a chiral cyanide anion. Various α-amido sulphone substrates (alkyl, aryl and heteroaryl) can be transformed into the optically enriched Strecker products, α-aminonitriles, with excellent yields and enantioselectivities. Moreover, the robust nature of the catalyst enables a 'one-pot' synthesis of enantiomerically pure α-amino acids starting from α-amido sulphones and simple catalyst recycling. These features can make this protocol easily adaptable to the practical synthesis of unnatural α-amino acids. © 2012 Macmillan Publishers Limited. All rights reserved.