View More View Less
  • 1 Department of Chemistry, York University, 4700 Keele Street, ON, Toronto, Canada M3J 1P3
  • 2 The University of Kansas Center for Chemical Methodologies and Library Development (KU-CMLD), 2034 Becker Drive, Del Shankel Structural Biology Center, Lawrence, KS 66047-3761, USA
  • 3 Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA
Restricted access

Abstract

The generation of stereochemically rich benzothiaoxazepine-1,1´-dioxides for enrichment of high-throughput screening collections is reported. Utilizing a microwave-assisted, continuous-flow organic synthesis platform (MACOS), scale-out of core benzothiaoxazepine-1,1´-dioxide scaffolds has been achieved on multigram scale using an epoxide opening/SNAr cyclization protocol. Diversification of these sultam scaffolds was attained via a microwave-assisted intermolecular SNAr reaction with a variety of amines. Overall, a facile, two-step protocol generated a collection of benzothiaoxazepine-1,1´-dioxides possessing stereochemical complexity in rapid fashion, where all eight stereoisomers were accessed from commercially available starting materials.

Supplementary Materials

    • Supplementary Material