Visible-Light-Mediated [2+2]-Cycloadditions for the Formation of Azetine-Based Macrocyclic Dimers

Abstract

Macrocyclic, dimeric lactones have known pharmacological activities that make them attractive synthetic targets but are typically synthesized following an iterative approach. Herein, we report a visible light-mediated approach to macrocyclic dimers that allows access to 1- and 2-azetine-containing dimeric lactones. Notably, up to 30-membered macrocycles are formed following this strategy that results in 1-azetine dimers via four consecutive triplet energy transfers, while 2-azetines are formed in a sequence relying on two consecutive triplet energy transfers. Computational investigations provide important insights into the reaction mechanism, suggesting that intermolecular [2+2]-cycloadditions are preferred under non-standard Curtin-Hammett conditions over the corresponding intramolecular reaction.

Publication
ACS Catalysis, in press
Ilia Kevlishvili
Ilia Kevlishvili
Postdoctoral Associate
Gianmarco Terrones
Gianmarco Terrones
Graduate Student
Heather J. Kulik
Heather J. Kulik
Professor of Chemical Engineering and Chemistry