In Situ Studies of Arylboronic Acids/Esters and R 3 SiCF 3 Reagents: Kinetics, Speciation, and Dysfunction at the Carbanion-Ate Interface.

Reagent instability reduces the efficiency of chemical processes, and while much effort is devoted to reaction optimization, less attention is paid to the mechanistic causes of reagent decomposition. Indeed, the response is often to simply use an excess of the reagent. Two reaction classes with ubiquitous examples of this are the Suzuki-Miyaura cross-coupling of boronic acids/esters and the transfer of CF 3 or CF 2 from the Ruppert-Prakash reagent, TMSCF 3 . This Account describes some of the overarching features of our mechanistic investigations into their decomposition. In the first section we summarize how specific examples of (hetero)arylboronic acids can decompose via aqueous protodeboronation processes: Ar-B(OH) 2 + H 2 O → ArH + B(OH) 3 . Key to the analysis was the development of a kinetic model in which pH controls boron speciation and heterocycle protonation states. This method revealed six different protodeboronation pathways, including self-catalysis when the pH is close to the p K a of the boronic acid, and protodeboronation via a transient aryl anionoid pathway for highly electron-deficient arenes. The degree of "protection" of boronic acids by diol-esterification is shown to be very dependent on the diol identity, with six-membered ring esters resulting in faster protodeboronation than the parent boronic acid. In the second section of the Account we describe 19 F NMR spectroscopic analysis of the kinetics of the reaction of TMSCF 3 with ketones, fluoroarenes, and alkenes. Processes initiated by substoichiometric "TBAT" ([Ph 3 SiF 2 ][Bu 4 N]) involve anionic chain reactions in which low concentrations of [CF 3 ] - are rapidly and reversibly liberated from a siliconate reservoir, [TMS(CF 3 ) 2 ][Bu 4 N]. Increased TMSCF 3 concentrations reduce the [CF 3 ] - concentration and thus inhibit the rates of CF 3 transfer. Computation and kinetics reveal that the TMSCF 3 intermolecularly abstracts fluoride from [CF 3 ] - to generate the CF 2 , in what would otherwise be an endergonic α-fluoride elimination. Starting from [CF 3 ] - and CF 2 , a cascade involving perfluoroalkene homologation results in the generation of a hindered perfluorocarbanion, [C 11 F 23 ] - , and inhibition. The generation of CF 2 from TMSCF 3 is much more efficiently mediated by NaI, and in contrast to TBAT, the process undergoes autoacceleration. The process involves NaI-mediated α-fluoride elimination from [CF 3 ][Na] to generate CF 2 and a [NaI·NaF] chain carrier. Chain-branching, by [(CF 2 ) 3 I][Na] generated in situ (CF 2 + TFE + NaI), causes autoacceleration. Alkenes that efficiently capture CF 2 attenuate the chain-branching, suppress autoacceleration, and lead to less rapid difluorocyclopropanation. The Account also highlights how a collaborative approach to experiment and computation enables mechanistic insight for control of processes.