Base-mediated selective synthesis of diversely substituted N-heterocyclic enamines and enaminones by the hydroamination of alkynes

J Org Chem. 2012 Jul 6;77(13):5633-45. doi: 10.1021/jo300782n. Epub 2012 Jun 22.

Abstract

Regio- and stereoselective alkynylation of various N-heterocycles 1a-l using potassium and cesium salts in DMSO is described. Terminal alkynes 2a-k and internal alkynes 4a-f provided the kinetically stable Z-enamines 3a-l and 5a-i in good to excellent yields using KOH at 120 °C. Addition of heterocyclic amines to 1,3- and 1,4-diethynylbenzene 6a-b provided the mixture of E/Z isomers with KOH; however, with Cs(2)CO(3) selectively Z-isomers 7ab-db were obtained by the hydroamination at one triple bond. This developed methodology also provides an easy and novel access for the synthesis of enaminones 10a-c. The detailed work also supports the formation of cis-isomer by preferential addition of o-haloarylalkynes followed by intramolecular C2 arylation in the copper-catalyzed tandem synthesis of indolo and pyrrolo[2,1-a]isoquinolines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Amination
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Hydroxides / chemistry*
  • Molecular Structure
  • Potassium Compounds / chemistry*
  • Stereoisomerism

Substances

  • Alkynes
  • Heterocyclic Compounds
  • Hydroxides
  • Potassium Compounds
  • potassium hydroxide