Stereoselective Substitution of Configurationally Labile α‐Bromo Aryl­acetates with Amines and Az­lactones by L‐Threonine‐Mediated Crystallization‐Induced Dynamic Resolution

Abstract

We developed a highly stereoselective C–N and C–C bond‐forming reaction by carrying out a crystallization‐induced dynamic resolution (CIDR) of α‐bromo arylacetates followed by a stereoselective substitution reaction with an amine or azlactone nucleophile. Applications of this synthetic method to the preparation of highly enantioenriched nitrogen‐containing six‐membered heterocycles and α,β‐disubstituted aspartates are also presented.

Asymmetric Catalytic Access to Piperazin-2-ones and Morpholin-2-ones in a One-Pot Approach: Rapid Synthesis of an Intermediate to Aprepitant

“…Although chiral pool and auxiliary based procedures have been developed, 13 the asymmetric catalytic methodologies reported so far to prepare piperazin-2-ones are limited and rare for C3-substituted morpholin-2-ones ( Scheme 1 ). Ir- 14 or Pd- 15 catalyzed hydrogenation of unsaturated piperazin-2-ones represents a versatile strategy to access piperazin-2-ones, bearing stereogenic centers at different positions of the heterocycle in a good to high level of steroselectivity ( Scheme 1 (a)).…”