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.

大环二聚内酯（macrocyclic dimeric lactones）具有药理活性，使其成为极具吸引力的合成靶标，但常规合成策略多采用迭代法构建大环结构。本文报道一种可见光介导的合成方法，可便捷制备环尺寸可达30的1-氮杂环丁烯（1-azetine）与2-氮杂环丁烯（2-azetine）类二聚内酯产物。1-氮杂环丁烯二聚产物通过四次连续三重态能量转移生成，而2-氮杂环丁烯二聚产物则经两次连续三重态能量转移得到。计算研究揭示了该反应的机理，结果表明在非标准科顿-哈蒙德（Curtin–Hammett）条件下，初始的分子间[2+2]环加成反应相较于对应的分子内反应更具优势，这一意外发现最终为大环二聚化提供了高效的反应路径。