Why trans- or cis-Dimethyl Fumarate Addition to 2,5-Dimethylpyrrole Gives Exclusively trans-7-Azanorbornane

Abstract

The addition mechanism of dimethyl fumarate into 2,5-dimethylpyrrole is explored using density functional theory (DFT) methods. Our calculations find that TpW(NO)(PMe3)(η(2)-3H-2,5-dimethylpyrrole) prefers to undergo two TpW(NO)(PMe3) migrations, two 1,5-hydride migrations, and one reductive elimination to isomerize into TpW(NO)(PMe3)(η(2)-1H-2,5-dimethylpyrrole), in which TpW(NO)(PMe3) plays a proton-transfer role. trans-Dimethyl fumarate and TpW(NO)(PMe3)(η(2)-1H-2,5-dimethylpyrrole) tend to adopt a concerted cycloaddition manner to afford trans-7-azanorbornane with a free-energy barrier of 21.8 kcal/mol. cis-Dimethyl fumarate and TpW(NO)(PMe3)(η(2)-1H-2,5-dimethylpyrrole) are the most likely to experience a concerted cycloaddition → ring opening → ring closing process to provide trans-7-azanorbornane in which the concerted cycloaddition and the ring-opening process are in dynamic equilibrium (with similar energy barriers of 21.5 and 21.9 kcal/mol, respectively). The presence of TpW(NO)(PMe3) not only promotes the cycloaddition of trans- or cis-dimethyl fumarate with 2,5-dimethylpyrrole by donating d-electrons of the W atom into the diene system of the Diels-Alder reaction, but also is favorable for the ring-opening process of the formed cis-7-azanorbornane. Furthermore, trans-azanorbornane is 7.4 kcal/mol more stable than cis-azanorbornane. Our calculations provide a new explanation of the addition of dimethyl fumarate with 2,5-dimethylpyrrole exclusively giving trans-7-azanorbornane.