Study on the Mechanism of Aza-Diels-Alder Reactions of N-Aryl-Imin and Some Vinyl Dericatires.

In its original form, the povarov reaction (PR) [1] involved a Lewis acid (LA) catalyzed aza-Diels-Alder (A-DA) reaction between a N-aryl imin and an electron rich dienophile, followed by a 1,3- hydrogen shift in the formal [4+2] cycloadduct 3 to yield a tetrahydroquindine 4 (Scheme 1). Over the past decade, various advances in the study of PR have been reported [2], including the broadening of its scope, progressing toward both the understanding of its reaction mechanism and its application in total synthesis [3]. In the present work,we perform a complete characterization of the reaction mechanism of the PR, as well as the main factors controlling the activation energy associated with the LA catalyzed A-DA reaction involved in these domino reactions. For this purpose a DFT study on these reactions were performed. At this computational level, the LA catalyzed A-DA reaction presents a two-step mechanism as a consequence of the large stabilization of corresponding zwitterion intermediate. The theoretical results indicated that the first step, which is associated with the nucleophilic attack of dienophiles in the imin carbon, constituents the rate-determining step of these A-DA reaction. Also analysis of the DFT-based reactivity indices of the reagents provides further explanation of the behaviors of the mechanism of the A-DA reaction involved in the povarov reaction.