Mechanistic Insights Into Carbamate Formation From Co2 And Amines: The Role Of Guanidine-Co2 Adducts

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 N-15 NMR is sensitive for zwitterion formation, complementing variable-temperature NMR studies.