An Efficient C-Si/C-H Cross-Coupling Reaction Enabled by a Radical Pathway

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Cross-coupling reactions are vital for synthesizing biaryls, but coupling aryl(trialkyl)silanes remains challenging due to the inert carbon-silicon bond.
• Existing methods often require harsh conditions or lack broad applicability, necessitating the development of milder, more efficient strategies.
• Aryl(trialkyl)silanes offer an environmentally benign alternative for cross-coupling due to silicon's low toxicity and the reaction's regioselectivity.

Purpose of the Study:

• To develop a novel copper-catalyzed cross-coupling method for aryl(trialkyl)silanes and aryl compounds.
• To establish an efficient and regioselective synthetic strategy for biaryl synthesis via a radical pathway.
• To investigate the reaction mechanism, including the roles of the copper catalyst and cesium fluoride (CsF).

Main Methods:

• Copper-catalyzed cross-coupling reaction utilizing aryl(trialkyl)silanes and aryl sulfonium salts.
• Employing a radical mechanism initiated by the copper catalyst and CsF.
• Conducting experimental and theoretical mechanistic studies to elucidate the reaction pathway.

Main Results:

• Efficient cross-coupling of aryl(trialkyl)silanes achieved under mild conditions.
• Broad substrate scope demonstrated, yielding various biaryl compounds.
• Successful application in synthesizing unsymmetrical fluorescence probes and late-stage functionalization of drug molecules.

Conclusions:

• A novel and efficient copper-catalyzed radical cross-coupling method for aryl(trialkyl)silanes has been developed.
• The reaction proceeds efficiently with aryl sulfonium salts as limiting reagents, offering a versatile synthetic strategy for biaryls.
• Mechanistic studies confirmed a radical pathway involving critical roles for the copper catalyst and CsF in radical generation and desilylation.