Late-stage and strain-accelerated oxidation enabled synthesis of haouamine A

Herein we report a new synthetic entry to the strained cyclophane alkaloid natural product, haouamine A. The successful strategy featured a rhodium-catalyzed diazo-insertion reaction to install the all-carbon quaternary center and a rhodium-catalyzed intramolecular aziridination reaction to establish the nitrogen-bearing stereocenter, of the target molecule. Most notably, a late-stage, site-selective and strain-accelerated oxidation of a "deoxygenated" macrocyclic intermediate was successfully implemented, and in doing so provided a novel solution to the infamous biphenol cyclophane system of haouamine A.