Development and Elucidation of a Pd-Based Cyclization-Oxygenation Sequence for Natural Product Synthesis.

Pd-catalyzed sequences involving oxidative addition, cyclization, and termination through intermolecular nucleophile capture have tremendous utility. Indeed, they can generate a plethora of different polycyclic structures possessing a diverse range of functionality. However, one area of deficiency for Pd /Pd variants is the ability to conclude them with oxygen-based species. Inspired by the recent discovery of one such reaction in the course of a total synthesis program, we delineate herein that it has significant strength, both in terms of substrate scope as well as the terminating oxygen nucleophile. As a result, the reaction proved critical in achieving total syntheses of two oxygenated natural products, one of which was prone to over-oxidation. Finally, a mechanistic proposal that accounts for its success is provided.