Enantioconvergent Cross-Nucleophile Coupling: Copper-Catalyzed Deborylative Cyanation

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Organoboron compounds are versatile reagents in organic synthesis.
• Their use as nucleophiles in cross-coupling is well-established.
• Their application in enantioconvergent transformations as racemic building blocks is underexplored.

Purpose of the Study:

• To demonstrate the direct use of alkylboronic pinacol esters in intermolecular enantioconvergent reactions.
• To develop a novel enantioconvergent deborylative cyanation reaction.
• To elucidate the mechanism of this transformation.

Main Methods:

• Copper-catalyzed reaction development.
• Mechanistic studies including electron paramagnetic resonance (EPR) spectroscopy.
• Computational studies using density functional theory (DFT).

Main Results:

• Successful development of an enantioconvergent deborylative cyanation of alkylboronic pinacol esters.
• High enantioselectivity achieved with broad functional group and heterocycle tolerance.
• Characterization of a key Cu(II)(CN)2 intermediate and support for a radical-relay mechanism.

Conclusions:

• Alkylboronic pinacol esters can be directly used in enantioconvergent transformations.
• The developed Cu-catalyzed cyanation offers a new route for asymmetric synthesis.
• The reaction proceeds via a proposed aniline-assisted radical-relay mechanism.