Convenient asymmetric synthesis of 1,3,4,6-tetrasubstituted 2,5-diketopiperazines

Abstract

A general and efficient method was developed for the asymmetric synthesis of 1,3,4,6-tetrasubstituted 2,5-diketopiperazines. The asymmetric nucleophilic substitution of L-amino acid-derived α-bromo tertiary amides with aliphatic primary amines followed by spontaneous cyclization provides a rapid access to diverse 1,3,4,6-tetrasubstituted-2,5-diketopiperazines with high diastereoselectivities of up to 99:1 dr.