All-cis Saturated 2,5-Diketopiperazines by a Diastereoselective Rhodium-Catalyzed Arene Hydrogenation

The direct hydrogenation of aromatic systems is a compelling tool to access saturated carbo- and heterocycles, an omnipresent motif in natural products, pharmaceuticals, and agrochemicals. Although a variety of methods have been established for simple arenes, the selective hydrogenation of aromatic 2,5-diketopiperazines (2,5-DKPs) has not been explored. We herein report a modular approach to perform a highly diastereoselective arene hydrogenation of symmetric 2,5-DKPs catalyzed by a rhodium complex. Twenty-eight saturated pentacyclic 2,5-DKPs were obtained in high yields with exquisite diastereoselectivities, exhibiting the hydrogen atoms in an all-cis arrangement. The high tolerance toward functional groups and the compatibility with existing stereogenic centers are key features of the transformation.