Synthesis of Azocanes from Piperidines via an Azetidinium Intermediate

Chemistry. 2021 Nov 25;27(66):16325-16328. doi: 10.1002/chem.202102739. Epub 2021 Oct 21.

Abstract

α-Trifluoromethyl azocanes are accessible from 2-(trifluoropropan-2-ol) piperidines by metal-free ring-expansion involving a bicyclic azetidinium intermediate. The opening of the azetidinium intermediate was achieved by various nucleophiles (amines, alcoholates, carboxylates, phosphonates, halides and pseudo-halides) with an excellent regio- diastereo- and enantioselectivity and in good yields. The relative configuration of the piperidines and azocanes were assigned and the deprotected azocanes offer opportunities for further derivatization.

Keywords: azetidinium; azocanes; fluorine; heterocycles; ring expansion.

MeSH terms

  • Amines*
  • Piperidines*

Substances

  • Amines
  • Piperidines