Nickel-Catalyzed Regio- and Enantioselective Hydroamination of Unactivated Alkenes Using Carbonyl Directing Groups
Changseok Lee, Hyung-Joon Kang, Huiyeong Seo and Sungwoo Hong*
*Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea,
Email: hongorg
kaist.ac.kr
C. Lee, H.-J. Kang, H. Seo, S. Hong, J. Am. Chem. Soc., 2022, 144, 9091-9100.
DOI: 10.1021/jacs.2c02343
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Abstract
A highly enantio- and regioselective Ni-catalyzed hydroamination of readily available unactivated alkenes bearing weakly coordinating native amides or esters provides β- or γ-amino acid derivatives and 1,2- or 1,3-diamines for both terminal and internal unactivated alkenes and a broad amine coupling partner scope. The mild reaction is well suited for late-stage functionalization.
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Details
The article discusses a novel method for the nickel-catalyzed regio- and enantioselective hydroamination of unactivated alkenes using carbonyl directing groups. This method is significant for synthesizing chiral amines, which are crucial in pharmaceuticals and natural products. The researchers developed a catalytic system that uses a chiral bisoxazoline-bound nickel species to achieve high regio- and enantioselectivity in hydroamination reactions. The method is effective for both terminal and internal unactivated alkenes and accommodates a wide range of amine coupling partners. The process is mild and suitable for late-stage functionalization of complex molecules, enabling the synthesis of enantioenriched β- or γ-amino acid derivatives and 1,2- or 1,3-diamines. Mechanistic studies revealed that the chiral nickel complex coordinates with native carbonyl groups to facilitate selective NiH insertion into alkenes. The optimized conditions and broad substrate scope demonstrate the method's versatility and potential utility in synthetic organic and medicinal chemistry. The study also includes kinetic and mechanistic investigations, providing insights into the reaction pathway and the role of the chiral ligand in determining selectivity. This work represents a significant advancement in the field of asymmetric hydroamination.
Key Words
β-amino amides, dimethoxymethylsilane
ID: J48-Y2022
