A Molecular Electron Density Theory Study of the Lewis Acid Catalyzed [3+2] Cycloaddition Reactions of Nitrones with Nucleophilic Ethylenes

Abstract

AbstractThe BF3Lewis acid (LA) catalyzed [3+2] cycloaddition (32CA) reaction of 1‐pyrroline‐1‐oxide (PNO) with 2,3‐dihydrofuran (DHF) has been studied within the molecular electron density theory (MEDT) at theωB97X‐D/6‐311G(d,p) computational level. Electron localization function (ELF) characterizes PNO and the corresponding PNO : BF3complex as zwitterionic species. Conceptual DFT indices allow classifying PNO and DHF as marginal electrophiles and strong nucleophiles, while the PNO : BF3complex is a strong electrophile. Consequently, while the non‐catalyzed 32CA reaction is non‐polar, the BF3catalyzed one has a high polar character, revealed by the analysis of the global electron density transfer (GEDT) at the transition state structures. The BF3catalyzed 32CA reaction, which is classified as of reverse electron density flux (REDF), presents highexostereoselectivity, and totalorthoregioselectivity. The presence of the BF3catalyst decreases the activation enthalpy of the 32CA reaction in dichloromethane by 7.5 kcal mol−1, as a consequence of the increase of the polar character of the reaction, in complete agreement with the experimentally observed acceleration.