Difluoromethylation of aryl and vinyl iodides

摘要

Selectively fluorinated molecules are important as materials, pharmaceuticals, and agrochemicals, but their synthesis by simple, mild, laboratory methods is challenging. We report a straightforward method for the cross-coupling of a difluoromethyl group with readily available reagents to form difluoromethylarenes. The reaction of electron-neutral, electron rich, and sterically hindered aryl and vinyl iodides with the combination of CuI, CsF and TMSCF2H leads to the formation of difluoromethylarenes in high yield with good functional group compatibility. This transformation is surprising, in part, because of the prior observation of the instability of CuCF2H.

主权项

1. A reaction mixture for forming a difluoromethyl aryl compound or a difluoromethyl vinyl compound, said reaction mixture comprising:
(i) a member selected from an X-substituted precursor of said difluoromethyl aryl compound and an X-substituted precursor of said difluoromethyl vinyl compound, said compound optionally further substituted at one or more positions wherein
X is a leaving group; (ii) a Cu source; (iii) a fluoride ion source; (iv) a silane having the formula:
R1R2R3SiCF2H, wherein
R1, R2 and R3 are independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy and substituted or unsubstituted aryl moieties.