Insights into chemoselective fluorination reaction of alkynals via N-heterocyclic carbene and Brønsted base cooperative catalysis

摘要: A systematically theoretical study has been carried out to understand the mechanism and chemoselectivity of N-heterocyclic carbene (NHC)-catalyzed fluorination reaction alkynals using density functional theory calculations. The calculated results reveal that contains several steps, i.e., formation actual catalyst NHC, nucleophilic attack NHC on carbonyl carbon atom a formyl group, Breslow intermediate, removal methyl carbonate group afford cumulative allenol C–F bond coupled with generation (SO2Ph)2N− anion, esterification accompanied (SO2Ph)2NH, dissociation from product. For intermediate via [1,2]-proton transfer process, apart direct proton mechanism, H2O- EtOH-mediated mechanisms were also investigated, free energy barriers for crucial steps can be significantly lowered by explicit inclusion protic media EtOH. Furthermore, multiple analyses have performed explore roles catalysts origin chemoselectivity. Noteworthily, in situ formed Bronsted base (BB) anion was found play an indispensable role indicating undergoes NHC-BB cooperatively catalytic which is remarkably different pathway proposed experimental references. This work provides case exploration dual catalysis chemistry, valuable rational design newly cooperative organocatalysis future.