Chemoenzymatic Synthesis of Substituted Azepanes by Sequential Biocatalytic Reduction and Organolithium-Mediated Rearrangement

Research output: Contribution to journalArticle

  • External authors:
  • Wojciech Zawodny
  • Sarah L. Montgomery
  • James R. Marshall
  • James D. Finnigan
  • Jonathan Clayden

Abstract

Enantioenriched 2-aryl azepanes and 2-arylbenzazepines were generated biocatalytically by asymmetric reductive amination using imine reductases or by deracemization using monoamine oxidases. The amines were converted to the corresponding N′-aryl ureas, which rearranged on treatment with base with stereospecific transfer of the aryl substituent to the 2-position of the heterocycle via a configurationally stable benzyllithium intermediate. The products are previously inaccessible enantioenriched 2,2-disubstituted azepanes and benzazepines.

Bibliographical metadata

Original languageEnglish
Pages (from-to)17872-17877
Number of pages6
JournalJournal of the American Chemical Society
Volume140
Issue number51
Early online date6 Dec 2018
DOIs
Publication statusPublished - 26 Dec 2018