Density functional theory computations have been performed to elucidate the mechanism of the catalytic asymmetric aza-electrocyclizations of aza-ortho-quinone methides. Our computations demonstrate that protonation of the N-terminus of 1-azatriene π system by the phosphoramide catalyst deactivates the substrate toward ring closure, as it disrupts conjugation of the nitrogen lone pair, which stabilizes the transition structure. Theory suggests an alternate mode of catalysis, one involving protonation of the N-protecting sulfonamide group of the aza-ortho-quinone methide precursors. Protonation of the protecting group renders the triene π system more electron deficient, reducing closed shell repulsion and enhancing the stabilizing effect of lone pair conjugation at the transition state. Upon proton transfer, the catalyst forms an ion pair with the aza-ortho-quinone substrate that is responsible for asymmetric induction. Based on our computations, we propose a qualitative model that rationalizes the stereoselectivity of these azatriene ring closures.

Computational investigation of the mechanism and stereoselectivity of the asymmetric organcatalytic azaelectrocyclizations of aza-othro-quinone methides

251st National Meeting (2016)

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