Kinetic Resolution of 2-Substituted Indolines by N-Sulfonylation using an Atropisomeric 4-DMAP-N-oxide Organocatalyst

James I Murray; Nils J Flodén; Adriano Bauer; Nico D Fessner; Daniel L Dunklemann; Opetoritse Bob-Egbe; Henry S Rzepa; Thomas Bürgi; Jeffery Richardson; Alan C Spivey

doi:10.1002/anie.201700977

Kinetic Resolution of 2-Substituted Indolines by N-Sulfonylation using an Atropisomeric 4-DMAP-N-oxide Organocatalyst

Angew Chem Int Ed Engl. 2017 May 15;56(21):5760-5764. doi: 10.1002/anie.201700977. Epub 2017 Apr 26.

Affiliations

¹ Department of Chemistry, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
² Université de Genève, Département de Chimie Physique, Quai Ernest-Ansermet 30, 1211, Genève 4, Switzerland.
³ Eli Lilly and Company Limited, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK.

PMID: 28444918
DOI: 10.1002/anie.201700977

Abstract

The first catalytic kinetic resolution by N-sulfonylation is described. 2-Substituted indolines are resolved (s=2.6-19) using an atropisomeric 4-dimethylaminopyridine-N-oxide (4-DMAP-N-oxide) organocatalyst. Use of 2-isopropyl-4-nitrophenylsulfonyl chloride is critical to the stereodiscrimination and enables facile deprotection of the sulfonamide products with thioglycolic acid. A qualitative model that accounts for the stereodiscrimination is proposed.

Keywords: asymmetric catalysis; indoline; kinetic resolution; organocatalysis; sulfonylation.

Publication types

Research Support, Non-U.S. Gov't