Visible-Light-Mediated Macrocyclization for the Formation of Azetine-Based Dimers

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.