Photochemical Macrolactonization of Hydroxyaldehydes via C-H Bromination.

Macrolactones are structurally important motifs that are found in a variety of natural products. While conventional approaches to their synthesis involve the use of seco acids with condensing agents or activators, methods based on hydroxyaldehydes as substrates remain relatively unexplored. Furthermore, the development of macrolactonization reactions that proceed via radical processes is still in its infancy, and to date, examples that use hydroxyaldehydes have not yet been reported. In this study, a photochemical macrolactonization of hydroxyaldehydes via in-situ-generated acyl bromide intermediates has been developed. Lactones with ring sizes ranging from 7-21 were successfully obtained in a good yield. The present photochemical radical macrolactonization therefore represents a promising tool for the synthesis of natural products.