Enantioselective Deaminative Alkylation of Amino Acid Derivatives with Unactivated Olefins

Herein, we report the first Ni-catalyzed enantioselective deaminative alkylation of amino acid and peptide derivatives with unactivated olefins. Key for success was the discovery of a new sterically encumbered bis(oxazoline) ligand backbone, thus offering a de novo technology for accessing enantioenriched sp(3)-sp(3) linkages via sp(3) C-N functionalization. Our protocol is distinguished by its broad scope and generality across a wide number of counterparts, even in the context of late-stage functionalization. In addition, an enantioselective deaminative remote hydroalkylation reaction of unactivated internal olefins is within reach, thus providing a useful entry point for forging enantioenriched sp(3)-sp(3) centers at remote sp(3) C-H sites.

Automated summary

Here, we report the first Ni-catalyzed enantioselective deaminative alkylation of amino acid and peptide derivatives with unactivated olefins. A new sterically encumbered bis(oxazoline) ligand backbone was discovered, offering a de novo technology for accessing enantioenriched sp(3)-sp(3) linkages via sp(3) C-N functionalization. This protocol has a broad scope and generality, even applicable for late-stage functionalization. Additionally, an enantioselective deaminative remote hydroalkylation reaction of unactivated internal olefins is achievable, providing an entry point for forging enantioenriched sp(3)-sp(3) centers at remote sp(3) C-H sites.