Synthesis of Chiral α-Amino Tertiary Boronates via the Catalytic Enantioselective Nucleophilic Borylation of Dialkyl Ketimines

The catalytic enantioselective nucleophilic borylation of ketimines is reported. A series of acyclic dialkyl ketimines reacted efficiently with bis(pinacolato)diboron in the presence of a copper(I)/chiral N-heterocyclic carbene catalytic system to furnish optically active alpha-amino tertiary boronates with high enantioselectivity (up to 99% ee). The products can be converted into peptidylboronic acid derivatives that bear bulky aliphatic substituents, compounds that are difficult to synthesize by other methods. Density functional theory calculations indicated that the enantioselectivity-determining step involves noncovalent interactions that recognize the prochiral dialkyl ketimine, leading to highly efficient enantiodiscrimination.

Automated summary

The study introduces a novel catalytic enantioselective nucleophilic borylation reaction of ketimines, leading to the efficient synthesis of optically active alpha-amino tertiary boronates with high enantioselectivity. The products can be further converted into peptidylboronic acid derivatives that are difficult to synthesize by other methods. Density functional theory calculations suggest that noncovalent interactions play a crucial role in determining the enantioselectivity of this reaction.