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

Abstract

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 3,5diarylisoxazoles have been investigated theoretically with the aid of density functional theory (DFT) calculations. With Cp*Rh III as the catalyst, the Ndirected 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 Ag 2 CO 3 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 heterodimetalliccatalyzed reactions.

Metal/Metal Dual Catalysis in C−H Activation

“…DFT calculations revealed that a Pd/Cu dinuclear intermediate was possibly involved during the formation of 16 b. [16] Recently, Mashima and co-workers reported an allylic CÀ H acyloxylation of terminal alkenes with 4-nitrobenzoic acid employing a low loading of bidentate-sulfoxide-ligated palladium as catalyst (Scheme 8). [17] Remarkably, the catalytic activity…”

Transition Metal‐Mediated Functionalization of Isoxazoles: A Review

“…[12] In 2020, Liu and co-workers carried out a detailed study on the role of Ag(I) and Cu(II) salts as cocatalysts in this site-selective CÀ H alkenylation of isoxazoles. [13] Based on DFT calculations, they proved that strong interaction between cationic Rh(III) catalyst and N-atom of isoxazole results in the isoxazole directed CÀ H alkenylation at the proximal aryl ring. The rate-determining step for this reaction is found to be the olefin insertion step, with an overall Gibbs energy barrier of 21.1 kcal/ mol.…”

“…In the case of Pd(II)-Cu(II) combination, a strong coordination of isoxazolyl nitrogen to the copper center facilitates the C(7)-H bond functionalization. [13]…”

“…With Pd(OAc) 2 and Cu(OTf) 2 combination, the strong coordination interaction between the nitrogen atom of the directing group and the copper centre in heterobimetallic PdÀ Cu-catalyst directs the process towards the activation and alkenylation at the neighboring aryl ring instead of the C(4)À H alkenylation. [13] Among various DGs used to direct CÀ H activation by effective coordination with the catalyst, carboxylic acid group as a traceless directing group has attained particular attention mainly due to its weak coordination facilitating the easy release of the catalyst and its ease of removal after the CÀ H functionalization. [37] Nakamura and co-workers, in 2019, reported a carboxylate-directed, Rh(III)-catalyzed CÀ H functionalization of isoxazoles with alkynes leading to C-5 alkenylated products by one-pot hydroarylation followed by decarboxylation (Scheme 27).…”

The synthesis of pyrrole from C4‐olefinated isoxazole catalyzed by ruthenium: A density functional theory study

“…The C4‐olefinated product ( 1 ) could successfully elaborated to yield densely functionalized pyrrole ( 2 ) catalyzed by RuCl 3 and Cu(OAc) 2 cooperatively (Scheme 1). Liu et al [ 9 ] have studied the elaborate mechanisms on the C‐4 alkenylation of isoxazole and explored the origin for the regioselectivity in this reaction by employing density functional theory (DFT) calculations. However, the corresponding mechanisms from 1 to 2 were not reported.…”