Oxidative Addition as the Selectivity-Determining Step in Gold(I)-Catalyzed Cross-Dehydrogenative Coupling of Arenes

Area of Science:

• Organic Chemistry
• Catalysis
• Computational Chemistry

Background:

• Gold(I) complexes catalyze cross-dehydrogenative heterocoupling (hetero-CDC) of arenes to form heterobiaryls.
• The mechanistic basis for chemoselectivity, favoring hetero- over homocoupling, remains unclear.

Purpose of the Study:

• To elucidate the mechanistic origins of chemoselectivity in Au(I)-catalyzed hetero-CDC reactions.
• To investigate the role of the gold(I) oxidation step in determining reaction outcomes.

Main Methods:

• Density functional theory (DFT) calculations were employed.
• Analysis of key reaction steps including C-H activation, oxidation, and reductive elimination.
• Investigation of the gold(I) oxidation mechanism by hypervalent iodine(III) oxidants.

Main Results:

• The gold(I) oxidation step, not previously considered critical, decisively influences chemoselectivity.
• Electron-poor arenes exhibit a lower gold(I) oxidation barrier, promoting their initial C-H activation.
• A novel oxidation mechanism, double hypervalent-twist-assisted oxidative addition (DHTA-OA), was identified.

Conclusions:

• The initial C-H activation selectivity is governed by the subsequent gold(I) oxidation step.
• DFT calculations provide crucial insights into the complex mechanism of hetero-CDC reactions.
• Understanding this mechanism enables rational design of selective catalytic systems for heterobiaryl synthesis.