Theoretical investigations toward the [3 + 2]-dipolar cycloadditions of nitrones with vinyldiazoacetates catalyzed by Rh2(R-TPCP)4: mechanism and enantioselectivity

Abstract

The mechanism of Rh₂(R-TPCP)₄-catalyzed [3 + 2]-dipolar cycloadditions between vinyldiazoacetate and nitrone to form 2,5-dihydroisoxazole has been studied by ONIOM methodology calculations including density functional theory and semi-empirical PM6 theory. This mechanism begins with carbenoid formation catalyzed by a rhodium catalyst, followed by vinylogous addition/cyclization of an iminium to construct a five-membered ring isoxazolidines, and followed by the functionalization processes of 1,3-hydride abstraction/proton transfer to generate 2,5-dihydroisoxazoles. The calculated results indicate a distinct stepwise fashion of this [3 + 2]-cycloaddition because of the extremely transient intermediate that emerged in the vinylogous reaction, and the cyclization of iminium addition is deemed to be the enantio-controlling step. According to analysis of thermodynamic information, the process of protonation has the highest energy barrier in this catalytic cycle and is determined as the rate-controlling step. A higher enantioselective formation of (R)-2,5-dihydroisoxazole derived from the reaction between aryl nitrone and s-trans vinylcarbenoid is evaluated. What's more, we kinetically analyze the enantioselectivity of this complete catalytic cycle by the AUTOF program and provide the reactivity trends with an activation strain model.