posted on 2024-03-04, 17:24authored byCody H. Ng, Scott L. Kim, Ilia Kevlishvili, Gianmarco G. Terrones, Emily R. Wearing, Heather J. Kulik, Corinna S. Schindler
Macrocyclic dimeric lactones have pharmacological activities
that
make them attractive synthetic targets, but typical synthetic strategies
employ an iterative approach to construct the macrocycle. Herein,
we report a visible-light-mediated approach that enables facile access
to 1- and 2-azetine-based dimeric lactones of up to 30-membered ring
macrocycles. These products form via four consecutive triplet energy
transfers for 1-azetine dimeric products and two consecutive triplet
energy transfers for 2-azetine dimeric products. Computational investigations
provide insights into the mechanism of this reaction, consistent with
an unexpected initial intermolecular [2 + 2]-cycloaddition being preferred
under nonstandard Curtin–Hammett conditions over the corresponding
intramolecular reaction, which ultimately enables an efficient reaction
pathway for macrocyclic dimerization.