52. Mechanism and stereospecificity of Z-enamide synthesis from salicylaldehydes with isoxazoles using DFT calculations

Ling, B.;* Jiang, Y.-Y.; Liu, Y.; Liu, P.; Liu, R.;* Bi, S.* J. Organomet. Chem. 2019, 903, 120981. Download Link

Abstract: A mechanistic study on Rh-catalyzed synthesis of stereospecific Z-enamide from salicyladehydes and isoxazoles has been performed with DFT calculations. The aldehydic CeH bond activation was found directed by anionic phenolic group rather than neutral phenolic hydroxyl, which reasonably rationalizes the reversibility of the CeH bond activation. Direct ring-opening rather than NeO oxidative addition of isoxazole, and subsequent CeC reductive elimination generate the stable tripodal intermediate that has been demonstrated by LC-MS analysis. Finally, sequential amino and phenolic protonations of the tripodal species produce the product Z-enamide. Stereospecificity of Z-enamide can be attributed to the rigid carbon-carbon double bond formed by direct ringopening of isoxazole. The rate-determining process is found to include the directing ring-opening and CeN reductive elimination with an overall barrier of 26.7 kcal/mol.