Insights into the Mechanisms and Chemoselectivities of Carbamates and Amides in Reactions Involving Rh(II)-Azavinylcarbene: A Computational Study.

Abstract

Reactions involving Rh(II)-azavinylcarbenes (Rh(II)-AVCs) to synthesize nitrogen-containing compounds have attracted significant research interest. Despite the importance of these reactions, controlling the chemoselectivities in the reactions involving Rh(II)-AVC remains a challenge. To understand the mechanisms and factors controlling the chemoselectivities between N-H and C═O groups of carbamates and amides in reactions involving Rh(II)-AVC, computational studies were employed. The results reveal that not only the greater nucleophilicity of the N-H group than that of the carbonyl group, but also the presence of H-bonding interactions, could favor the addition of the N-H group of primary carbamates to Rh(II)-AVC. However, for secondary carbamates and amides, they could undergo either chemoselective N-H or C═O addition. Secondary carbamates with less steric hindrance, such as oxazolidinone, prefer the N-H addition mode. However, a switch in chemoselectivity (preference for the C═O addition) was revealed for the sterically hindered secondary carbamates/amides. In addition, a possible O-H addition pathway via the keto-enol tautomerization for isatin and isatoic anhydride was disregarded due to the energetically demanding barrier. Instead, a pathway involving the chemoselective C═O addition, formal [3 + 2] cycloaddition, followed by ring opening was proposed. The origins of the chemoselectivity and the factors responsible were addressed.