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

J Am Chem Soc. 2018 Dec 26;140(51):17872-17877. doi: 10.1021/jacs.8b11891. Epub 2018 Dec 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azepines / chemical synthesis*
  • Biocatalysis
  • Imines / chemistry
  • Lithium / chemistry
  • Monoamine Oxidase / chemistry
  • Organometallic Compounds / chemistry
  • Oxidation-Reduction
  • Oxidoreductases Acting on CH-NH Group Donors / chemistry
  • Stereoisomerism

Substances

  • Azepines
  • Imines
  • Organometallic Compounds
  • Lithium
  • Monoamine Oxidase
  • Oxidoreductases Acting on CH-NH Group Donors