Enantioselective synthesis of δ-Boryl chiral amines/amides via copper-catalyzed sequential hydroboration hydroamination/hydroaminocarbonylation of methylenecyclopropanes

• Published in: Journal of catalysis Vol. 450; p. 116280
• Main Authors: Yuan, Yang, Ge, Fangbei, Yang, Ting, Wu, Xiao-Feng
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.10.2025
• Subjects: Carbonylation; Copper; Enantioselective; Methylenecyclopropanes; δ-boryl chiral amides; Methylenecyclopropanes; Carbonylation; Enantioselective; δ-boryl chiral amides; Copper
• ISSN: 0021-9517
• DOI: 10.1016/j.jcat.2025.116280

[Display omitted] •A new copper-catalyzed sequential hydroboration-hydroamination and hydroboration-hydroaminocarbonylation of methylenecyclopropanes.•An efficient method for the enantioselective synthesis of δ-boryl chiral amines and amides.•Copper-catalyzed ring-opening hydroboration through homoallylic boronate intermediate. We report the development of a copper-catalyzed asymmetric synthesis of δ-boryl chiral amines and amides via sequential ring-opening reactions of methylenecyclopropanes (MCPs). Using Cu(OAc)2 /(R)-DTBM-Segphos catalytic system, MCPs undergo hydroboration-hydroamination with HBpin and hydroxylamine esters to produce δ-boryl chiral amines in good yields (up to 85 %) and excellent enantioselectivities (up to >99 % ee). The method shows broad substrate scope, tolerating various functional groups and structural motifs. Additionally, CuCl/(S,S)-Ph-BPE enables sequential hydroboration-hydroaminocarbonylation of MCPs under CO atmosphere, affording δ-boryl chiral amides with high enantioselectivity (up to 99 % ee). The synthetic utility of these methods is highlighted through various stereospecific transformations of the products. Mechanistic studies indicate that these transformations proceed via copper-catalyzed ring-opening hydroboration to form homoallylic boronate intermediates, followed by enantioselective hydroamination or hydroaminocarbonylation steps to produce the final δ-boryl chiral amines and amides.