DFT studies on the diastereoselectivity of four-component Ugi reaction

Abstract

In this study, mechanism and stereochemistry of four-component Ugi reaction was investigated theoretically. Structures of reagents, products, intermediates, and transition states were optimized at B3LYP/6-31[Formula: see text]G(d,p) level of theory. Mechanism and stereoselectivity of the reaction depended on several processes, including bond rotation, ring closure ring opening, acid-base, nucleophile-electrophile competitions, and rearrangements. These diverse phenomena were studied to provide a clearer picture of the mechanism of this valuable reaction, especially in terms of stereochemistry considerations. According to the results, (E)-oxazolidinols were considered as proper intermediates in Ugi reaction mechanism. In addition, the key point of diastereoselectivity of the reaction was under kinetic and thermodynamic controls of nucleophilic attack of isocyanide to less hindered re-face (E[Formula: see text] compared to 10.19[Formula: see text]kcal/mol for si-face) of chiral (E)-iminium ion.