Mechanistic insights into carbamate formation from CO2 and amines: the role of guanidine–CO2 adducts

Abstract

Capture of CO₂ 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–CO₂ adducts are able to actively transfer the carboxylate group to various substrates. Here we report a detailed investigation of zwitterionic TMG–CO₂, including isolation, NMR behavior, reactivity, and mechanistic consequences in carboxylation of aniline-derivatives. Our computational and experimental mechanistic analysis shows that the reversible TMG–CO₂ zwitterion is not a direct carboxylation agent. Instead, CO₂ dissociates from TMG–CO₂ before a concerted carboxylation occurs, where the role of the TMG is to deprotonate the amine as it is attacking a free CO₂. This insight is significant, as it opens a rational way to design new synthesis strategies. As shown here, nucleophiles otherwise inert towards CO₂ can be carboxylated, even without a CO₂ atmosphere, using TMG–CO₂ as a stoichiometric source of CO₂. We also show that natural abundance ¹⁵N NMR is sensitive for zwitterion formation, complementing variable-temperature NMR studies.