Homologation of the Fischer Indolization: A Quinoline Synthesis via Homo-Diaza-Cope Rearrangement

Angew Chem Int Ed Engl. 2020 Nov 9;59(46):20485-20488. doi: 10.1002/anie.202005798. Epub 2020 Sep 7.

Abstract

We disclose a new Brønsted acid promoted quinoline synthesis, proceeding via homo-diaza-Cope rearrangement of N-aryl-N'-cyclopropyl hydrazines. Our strategy can be considered a homologation of Fischer's classical indole synthesis and delivers 6-membered N-heterocycles, including previously inaccessible pyridine derivatives. This approach can also be used as a pyridannulation methodology toward constructing polycyclic polyheteroaromatics. A computational analysis has been employed to probe plausible activation modes and to interrogate the role of the catalyst.

Keywords: DFT calculations; Fischer indolization; annulation; cyclopropane; quinolines; rearrangements.

Publication types

  • Research Support, Non-U.S. Gov't