摘要：Department of Chemistry and the HongKong, Branch of Chinese National Engineering Research Centre forTissue Restoration & Reconstru
转自：康龙化成
Catalytic EnantioselectiveNucleophilic Amination of α-Halo Carbonyl Compounds with Free Amines
Zhiyang Li, Baocheng Wang, Shuaixin Fan,Chaoshen Zhang, and Jianwei Sun
Department of Chemistry and the HongKong, Branch of Chinese National Engineering Research Centre for Tissue Restoration & Reconstruction,The Hong Kong University of Science and Technology, Kowloon, Hong Kong SAR999077, China;
—10.1021/jacs.4c12069
Recommended by Qifei Hu_DPC
KEYWORDS: Enantioselective Amination (反应类型), Substitution(反应类型), C(sp3)-N (成键类型),α-HaloCarbonyl Compounds (原料),free amine (原料),Chiral phosphoric acids (催化剂), chiralamine (产物)
ABSTRACT: Catalyticenantioselective substitution of the readily available racemic α-halo carbonylcompounds by nitrogen nucleophiles represents one of the most convenient anddirect approaches to access enantioenriched α-amino carbonyl compounds.Distinct from the two available strategies involving radicals and enolate ions,herein we have developed a new protocol featuring an electronically oppositeway to weaken/cleave the carbon−halogen bond. A suitable chiral anion-basedcatalyst enables effective asymmetric control over the key positively chargedintermediates. This protocol not only allows free amines to serve asnucleophiles but also permits different types of carbonyl compounds (ketones,esters, and amides) to participate in the enantioselective C−N bond formation,thereby providing a valuable complement to the known strategies that arelimited to certain carbonyl substrates and/or nitrogen nucleophiles.Preliminary studies indicated that an SN2pathway is operational and kinetic resolution is involved.
Background
ReactionScope for Esters
Proposed Mechanism
ChiralN-Boc Amine Synthesis
Recently,Prof. Jianwei Sun and his group reported a new catalytic strategy for thedirect enantioselective nucleophilic amination of α-halo carbonyl compounds viakinetic resolution. A range of α-amino ketones, esters, and amides wereefficiently synthesized with high enantioselectivity from readily availablestarting materials under mild conditions.
来源：新浪财经
