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

Abstract

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.