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

Amination of C(sp3)-H bonds is a powerful tool to introduce nitrogen into complex organic frameworks in a direct manner. Despite significant advances in catalyst design, full site- and enantiocontrol in complex molecular regimes remain elusive using established catalyst systems. To address these challenges, we herein describe a new class of peptide-based dirhodium(II) complexes derived from aspartic acid-containing ß-turn-forming tetramers. This highly modular system can serve as a platform for the rapid generation of new chiral dirhodium(II) catalyst libraries, as illustrated by the facile synthesis of a series of 38 catalysts. Critically, we present the first crystal structure of a dirhodium(II) tetra-aspartate complex, which unveils retention of the ß-turn conformation of the peptidyl ligand; a well-defined hydrogen-bonding network is evident, along with a near-C4 symmetry that renders the rhodium centers inequivalent. The utility of this catalyst platform is illustrated by the enantioselective amination of benzylic C(sp3)-H bonds, in which state-of-the-art levels of enantioselectivity up to 95.5:4.5 er are obtained, even for substrates that present challenges with previously reported catalyst systems. Additionally, we found these complexes to be competent catalysts for the intermolecular amination of N-alkylamides via insertion into the C(sp3)-H bond α to the amide nitrogen, yielding differentially protected 1,1-diamines. Of note, this type of insertion was also observed to occur on the amide functionalities of the catalyst itself in the absence of the substrate but did not appear to be detrimental to reaction outcomes when the substrate was present.

Expedient access to substituted 3-amino-2-cyclopentenones by dirhodium-catalyzed [3+2]-annulation of silylated ketene imines and enoldiazoacetates.

In a reaction that proceeds under mild conditions with remarkable functional group tolerance, structurally diverse 3-amino-2-cyclopentenones bearing a quaternary carbon at the 4-position have been synthesized through a formal [3+2]-cycloaddition reaction of silylated ketene imines (SKIs) and enoldiazoaceates by dirhodium catalysis.

Diazoacetoacetate enones for the synthesis of diverse natural product-like scaffolds.

Diazoacetoacetate enones are a new class of Michael acceptors that enable the efficient construction of natural product-like scaffolds. Through their Michael addition reactions, including those with silyl enol ethers, indoles, pyrroles, and amines, δ-functionalized diazoacetoacetates are formed in high yield and with overall operational efficiency. Subsequent catalytic dinitrogen extrusion reactions provide access to a diverse series of natural product-like carbo- and heterocyclic ring systems in only three steps from commercial materials.