Benzodiazepin-2,5-diones are privileged scaffolds in medicinal chemistry and we and others have explored alkylation of the derived enolates. Recently Farran et al. (Eur. J. Org. Chem. 2011  , 2043) reported that treatment of valine-derived (S)-1a  with LiHMDS led to (R)-2a in 86% ee. The substrate scope of this fascinating enantioselective ring-contraction was not reported however, due to difficulties in preparing analogs from other amino acids. In this paper we will show that analogs featuring R1 = Me (e.g. 3a  -d  ) are easily prepared from various amino acids, and undergo highly enantioselective deprotonative ring contraction to 4a ?-?d  . An explanation of the stereochemical course of the reactions of (S)-1a  and 3a  -d  will be offered.

Enantioselective ring-contraction of benzodiazepin-2,5-dione enolates

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.