Synthesis of L–Au(I)–CF₂H Complexes and Their Application as Transmetalation Shuttles to the Difluoromethylation of Aryl Iodides

Abstract

We describe herein two alternative protocols to efficiently prepare difluoromethylgold(I) complexes bearing ancillary ligands with different electronic and steric properties. LAu−OX (X = H and t-Bu) species, formed in the presence of base, have been identified as intermediate complexes involved in these transformations. The application of these compounds as "CF 2 H transmetalation shuttles" from gold to palladium has been demonstrated in a Pd-catalyzed difluoromethylation reaction of aryl iodides, in which the Au-to-Pd transfer of "CF 2 H" is feasible under stoichiometric conditions. These findings will pave the way for catalytic manifolds in gold chemistry.

A Difluoromethylation Reagent: Access to Difluoromethyl Arenes through Palladium Catalysis

“…4-Phenylphenol (5) was isolated in 64% yield when 1a was treated in the presence of K 2 HPO 4 and TEMPO. The formation of TEMPO adduct, O-(4-phenyl)phenyl TEMPO (6), was also detected via HRMS, with the results indicating the generation of 4-phenyl phenyl radical (Figure 1A(b)). Phenol product 5 did not form in the absence of TEMPO (Figure 1A(c)).…”

“…The first category includes radical difluoromethylation reagents (Scheme a), including HF 2 C–Br, 2-PySO 2 –CF 2 H, and HCF 2 –SO 2 Na . The second comprises a relatively large number of nucleophilic difluoromethylation reagents (Scheme b) that react with an aryl electrophile via – CF 2 H anion [HF 2 C–SiMe 3 , HF 2 C–AuPAr 3 , HF 2 C–SnBu 3 , HF 2 C–Ag­(SIPr), (HF 2 C) 2 Zn­(DMPU) 2 , and (HF 2 C) 2 Zn­(TMEDA)] or F 2 C:carbene intermediate (HF 2 C–Cl) . The third group consists of electrophilic difluoromethylation reagents (Scheme c), containing HF 2 C–I, HF 2 C–COF, HF 2 C–CI, BrF 2 C–COOEt, and Ph 3 P + CF 2 –COO – .…”