Mechanistic insights into carbamate formation from CO2and amines: The role of guanidine-CO2adducts

Abstract

Capture of CO2by 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-CO2adducts 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-CO2zwitterion is not a direct carboxylation agent. Instead, CO2dissociates from TMG-CO2before 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 CO2can be carboxylated, even without a CO2atmosphere, using TMG-CO2as a stoichiometric source of CO2. We also show that natural abundance15N NMR is sensitive for zwitterion formation, complementing variable-temperature NMR studies.