Rh(II)-catalyzed [4 + 3] Cycloaddition of Enaminones and Vinyl Diazo Esters: Synthesis of Functionalized 2,4-Diaryl-3 H -azepine-7-carboxylates

Abstract

Herein, we report a novel Rh(II)-catalyzed cyclization of enaminones with vinyl diazo esters for the synthesis of 2,4-diaryl-3H-azepine-7-carboxylates (DAAPCs). Under the optimized reaction conditions, enaminones 1 (1.0 equiv) were treated with vinyl diazo esters 2 (1.5 equiv) in the presence of Rh2(OAc)4 (5 mol%) in refluxing toluene for 10 h, affording the corresponding azepine derivatives 3 in moderate yields. Mechanistically, the reaction is proposed to proceed through the initial formation of a Rh(II)-carbenoid, followed by N–H insertion, a subsequent oxa-ene reaction, dehydration, and imine–enamine tautomerization, thereby enabling the construction of the seven-membered azepine scaffold. From a synthetic perspective, this transformation provides an efficient approach to the intermolecular alkenylation of carbonyl compounds. More importantly, it establishes a versatile platform for accessing structurally diverse azepine derivatives through a simple one-step reaction. Notably, this strategy enables the synthesis of 2,4-diaryl-3H-azepine-7-carboxylates, a class of compounds with potential biological activity. Furthermore, the present study expands the synthetic utility of vinyl diazo esters 2 by highlighting their potential as C3 synthons for the construction of azepine frameworks.