Mechanistic insights into carbamate formation from CO and amines: the role of guanidine-CO adducts

Capture of CO 2 by amines is an attractive synthetic strategy for the formation of carbamates. Such reactions can be mediated by superbases, such as 1,1,3,3-tetramethylguanidine (TMG), with previous implications that zwitterionic superbase-CO 2 adducts are able to actively transfer the carboxylate group to various substrates. Here we report a detailed investigation of zwitterionic TMG-CO 2 , including isolation, NMR behavior, reactivity, and mechanistic consequences in carboxylation of aniline-derivatives. Our computational and experimental mechanistic analysis shows that the reversible TMG-CO 2 zwitterion is not a direct carboxylation agent. Instead, CO 2 dissociates from TMG-CO 2 before a concerted carboxylation occurs, where the role of the TMG is to deprotonate the amine as it is attacking a free CO 2 . This insight is significant, as it opens a rational way to design new synthesis strategies. As shown here, nucleophiles otherwise inert towards CO 2 can be carboxylated, even without a CO 2 atmosphere, using TMG-CO 2 as a stoichiometric source of CO 2 . We also show that natural abundance 15 N NMR is sensitive for zwitterion formation, complementing variable-temperature NMR studies. This work explores the reactivity of a reversible superbase-CO 2 zwitterion, which can be used as a stoichiometric source of CO 2 .