General entry to asymmetric one-pot [N + 2 + n] cyclization for the synthesis of three- to seven-membered azacycloalkanes

J Org Chem. 2012 Sep 7;77(17):7212-22. doi: 10.1021/jo301495a. Epub 2012 Aug 20.

Abstract

Enantio- and diastereoselective one-pot synthesis of three- to seven-membered cis-azaheterocycles was achieved using a triggered asymmetric conjugate addition reaction of lithium amide with an enoate, followed by alkylation of the resulting lithium enolate with α,ω-dihaloalkane and N-alkylation. Isomerization of cis-azaheterocycles with a base yielded the trans-product, constituting a one-pot synthesis of cis-azacycles and a two-step synthesis of trans-azacycles. The four-step asymmetric synthesis of nemonapride highlights the general utility of the method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Cyclization
  • Cycloparaffins / chemical synthesis*
  • Cycloparaffins / chemistry
  • Molecular Structure
  • Stereoisomerism

Substances

  • Aza Compounds
  • Cycloparaffins