Regio-Selective C3- and N-Alkylation of Indolines in Water under Air Using Alcohols

J Org Chem. 2022 May 6;87(9):5603-5616. doi: 10.1021/acs.joc.1c03040. Epub 2022 Apr 13.

Abstract

We disclosed a regio-selective C-H and N-H bond functionalization of indolines using alcohols in water via tandem dehydrogenation of N-heterocycles and alcohols. A diverse range of N- and C3-alkylated indolines/indoles were accessed utilizing a new cooperative iridium catalyst. The practical applicability of this methodology was demonstrated by the preparative-scale synthesis and synthesis of a psychoactive drug, N,N-dimethyltryptamine. A catalytic cycle is proposed based on several kinetic experiments, series of control experiments and density functional theory calculations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols* / chemistry
  • Alkylation
  • Indoles / chemistry
  • Water*

Substances

  • Alcohols
  • Indoles
  • Water
  • indoline