Fluoroallylboration-olefination for the synthesis of (Z)-4,4-difluoropent-2-enoates and 5,5-difluoro-5,6-dihydropyran-2-ones

Horner-Wadsworth-Emmons (HWE) or Still-Gennari olefination of TBS-protected 3,3-difluoro-4-hydroxy-2-ones, derived from the difluoroallylboration of aldehydes, provides the Z-isomer of 4,4,-difluoropent-2-enoates. These, upon hydrolysis, followed by Yamaguchi cyclization, afford 5,5-difluoro-4-methyl-5,6-dihydro-α-pyrones in high yields.     

Asymmetric fluoroallylboration of aldehydes

Contrary to previous reports, the homologation of benzyloxydifluorovinyllithium with bulky chiral iodomethylboronates readily provides a series of chiral γ,γ-difluoroallylboronates. Asymmetric fluoroallylboration of aldehydes with a 2-phenylbornane-2,3-diol-derived reagent provides gem-difluorinated homoallyl alcohols in good yields and 77-95% ee. Preparation of a chiral α-pyrone in >99% ee has also been described.     

Nucleophilic trifluoromethylation of conjugate acceptors via phenyl trifluoromethyl sulfone

A mild procedure for the conjugate addition of the trifluoromethyl anion to activated Michael acceptors such as arylidenemalononitriles (15 examples) and arylidene Meldrum’s acids (9 examples) using phenyl trifluoromethyl sulfone through a reductive magnesium metal mediated procedure is described. The new methodology is used to prepare befloxatone, a reversible and selective monoamine oxidase A inhibitor.