What?: Industrial trifluoromethylation
Who?: Mulder et al. Boehringer Ingelheim Pharmaceuticals
Key reagent: methyl chlorodifluoroacetate (MCDFA) / KF / CuI , a system first described in 1991 (DOI)
Why should we care?: MCDFA is lot cheaper than other trifluoromethylation reagents
Downsides: reaction requires 4 eq. of MCDFA and stochiometric copper. MCDFA invites multiple alkylations on initial CF3 unit, resulting in polymeric mess. CF3- possibly in equilibrium with difluorocarbene, stoichiometric copper drives equilibrium back to desired end. Foam formation from carbon dioxide was also found to interfere with kilogram scale batch production.