Weak bases display better: kinetic deprotonative functionalization

Abstract

The C–H bond deprotonation and functionalization reaction represents the most frequently used method for C–C bond construction and also a vital mode of C–H bond activation. Great developments have been made recently in the catalytic C–C bond formation by using weakly acidic C–H compounds as nucleophiles. The strongly basic reagent or catalyst is the key factor in these reactions. If only the base is basic enough, the deprotonation of the weakly acidic C–H bonds, the formation of the carbanions and the following nucleophilic reactions occur according to the acid-base equilibrium theory. Even though a relative weak base is not strong enough for deprotonation, the carbanion still exists in the system, possibly in a very low concentration. Once the carbanion selectively undergoes a thermodynamically favoured transformation, its concentration goes down and thus starts the reestablishment of the deprotonation equilibrium. With the combination of the irreversible conversion of the carbanion and constant reestablishment of the equilibrium, the deprotonative functionalization of weakly acidic C–H bonds could be achieved slowly but continuously under relative weakly basic conditions. Distinct from the conventional deprotonative functionalization under strong base via a thermodynamically favoured carbanion intermediate, we suggest the descriptive name “kinetic deprotonative functionalization” for the reaction under relative weak conditions via the combination of the irreversible conversion of the carbanion and constant reestablishment of the equilibrium. Herein, we will briefly review the research status of deprotonative functionalization reactions and discuss the kinetic deprotonative functionalization reactions developed recently in our group.