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.

Automated summary

The direct hydrogenation of aromatic systems is an important method for obtaining saturated carbo- and heterocycles. This study reports a modular approach to efficiently and selectively hydrogenate 2,5-DKPs, resulting in high yields of saturated pentacyclic 2,5-DKPs.