Aspartyl β-Turn-Based Dirhodium(II) Metallopeptides for Benzylic C(sp3)-H Amination: Enantioselectivity and X-ray Structural Analysis

Aminationof C-(sp(3))-H bonds is a powerful toolto introduce nitrogen into complex organic frameworks in a directmanner. Despite significant advances in catalyst design, full site-and enantiocontrol in complex molecular regimes remain elusive usingestablished catalyst systems. To address these challenges, we hereindescribe a new class of peptide-based dirhodium-(II) complexes derivedfrom aspartic acid-containing beta-turn-forming tetramers. Thishighly modular system can serve as a platform for the rapid generationof new chiral dirhodium-(II) catalyst libraries, as illustrated bythe facile synthesis of a series of 38 catalysts. Critically, we presentthe first crystal structure of a dirhodium-(II) tetra-aspartate complex,which unveils retention of the beta-turn conformation of the peptidylligand; a well-defined hydrogen-bonding network is evident, alongwith a near-C (4) symmetry that renders therhodium centers inequivalent. The utility of this catalyst platformis illustrated by the enantioselective amination of benzylic C-(sp(3))-H bonds, in which state-of-the-art levels of enantioselectivityup to 95.5:4.5 er are obtained, even for substrates that present challengeswith previously reported catalyst systems. Additionally, we foundthese complexes to be competent catalysts for the intermolecular aminationof N-alkylamides via insertion into the C-(sp(3))-H bond alpha to the amide nitrogen, yielding differentiallyprotected 1,1-diamines. Of note, this type of insertion was also observedto occur on the amide functionalities of the catalyst itself in theabsence of the substrate but did not appear to be detrimental to reactionoutcomes when the substrate was present.