Exploring Cyclization Strategies to Access Stemona Alkaloids: Subtle Effects Influencing Reactivity in Intramolecular Michael Additions

Org Lett. 2021 Nov 5;23(21):8494-8498. doi: 10.1021/acs.orglett.1c03205. Epub 2021 Oct 22.

Abstract

This report investigates the fundamental basis for rather surprising patterns of reactivity in Brønsted acid-mediated cyclizations of pyrrole substrates bearing pendant Michael acceptors that were identified during syntheses of Stemona alkaloids. Integrated experimental and theoretical studies reveal the profound influence that substituent effects have on the viability of these transformations. Additionally, we identify that electronic effects, in addition to barrier-lowering secondary orbital interactions within transition states, account for the exclusive preference for 7-endo-trig cyclizations over 6-exo-trig cyclizations.

Publication types

  • Research Support, Non-U.S. Gov't