Expedient synthesis of α-(2-azaheteroaryl) acetates via the addition of silyl ketene acetals to azine-N-oxides

Org Lett. 2014 Jun 20;16(12):3336-9. doi: 10.1021/ol501359r. Epub 2014 Jun 2.

Abstract

A new and expedient synthesis of α-(2-azaheteroaryl) acetates is presented. The reaction proceeds rapidly under mild conditions via the addition of silyl ketene acetals to azine-N-oxides in the presence of the phosphonium salt PyBroP. This procedure affords diverse α-(2-azaheteroaryl) acetates which are highly desirable components/building blocks in molecules of pharmaceutical interest but are traditionally challenging to synthesize via contemporary methods. The reaction optimization and mechanism as well as a novel electronically enhanced PyBroP derivative are described.

MeSH terms

  • Acetals / chemical synthesis*
  • Acetals / chemistry
  • Acetates / chemical synthesis*
  • Acetates / chemistry
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Ethylenes / chemistry*
  • Ketones / chemistry*
  • Molecular Structure
  • Organophosphorus Compounds / chemistry*
  • Oxides / chemistry*
  • Silanes / chemistry*
  • Stereoisomerism

Substances

  • Acetals
  • Acetates
  • Aza Compounds
  • Ethylenes
  • Ketones
  • Organophosphorus Compounds
  • Oxides
  • Silanes
  • ketene