Distinct Roles of Ag(I) and Cu(II) as Cocatalysts in Achieving Positional-Selective C-H Alkenylation of Isoxazoles: A Theoretical Investigation.

For C-H alkenylation of aryl-substituted diarylisoxazoles, one mode is N-directed C-H alkenylation and the other is C-H alkenylation in the isoxazole ring. In this study, selective C-H alkenylations of 3,5-diarylisoxazoles have been investigated theoretically with the aid of density functional theory (DFT) calculations. With Cp*RhIII as the catalyst, the N-directed C-H alkenylation is preferred as a result of the stronger interaction energy caused by the nitrogen-directing effect. With Pd(OAc)2 as the catalyst and Ag2CO3 as the cocatalyst, their combination switches the regioselectivity to the C-H alkenylation in the isoxazole ring. The strong structural distortion involved in the competing N-directed olefin insertion transition state was found to suppress N-directed C-H alkenylation. With Pd(OAc)2 as the catalyst and Cu(OTf)2 as the cocatalyst, the N-directed C-H alkenylation becomes preferred due to the strong coordination of the nitrogen atom to the copper center. In particular, the structural and mechanistic information involved in the above two heterodimetallic Pd/Ag and Pd/Cu catalytic systems will help toward understanding and designing novel relevant heterodimetallic-catalyzed reactions.