Enantioselective Deaminative Alkylation of Amino Acid Derivatives with Unactivated Olefins

• Published in: Journal of the American Chemical Society Vol. 144; no. 3; pp. 1130 - 1137
• Main Authors: Sun, Shang-Zheng, Cai, Yue-Ming, Zhang, De-Liang, Wang, Jia-Bao, Yao, Hong-Qing, Rui, Xi-Yan, Martin, Ruben, Shang, Ming
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 26.01.2022; Amer Chemical Soc
• Subjects: Alkenes - chemistry; Alkylation; amino acids; Amino Acids - chemistry; Catalysis; Chemistry; Chemistry, Multidisciplinary; enantioselectivity; ligands; Molecular Structure; Nickel - chemistry; peptides; Physical Sciences; Science & Technology; Stereoisomerism; BORONIC ACIDS; LIGANDS; CROSS COUPLINGS; ARYL; REMOTE; C-H FUNCTIONALIZATION; BENZYLIC AMMONIUM-SALTS; REDUCTIVE ARYLATION; NICKEL-CATALYZED BORYLATION
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.1c12350

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.