A hexafluoroisopropanol (HFIP)-catalyzed difluoroalkylation of propargylic alcohols with difluoroenoxysilanes to access structurally diverse tetrasubstituted difluoroalkyl allenes has been developed. This convenient procedure enables the rapid construction of highly functionalized multisubstituted fluorinated allenes in a mild and straightforward way. Furthermore, the synthetic potential of this methodology has been demonstrated by the facile synthesis of various structurally interesting fluorinecontaining molecules such as gem-difluorosubstituted dihydropyran, tetrasubstituted CF 2 H-allene, and multisubstituted fluorinated cyclopentanone derivatives.

A TfOH-promoted synthesis of fluorinated polyfused heterocycles via the cascade cyclization of azadienes and difluoroenoxysilanes has been developed, leading to the facile construction of and 5,6-dihydrobenzo[h]quinolines. This one-pot formal [4 + 2] approach involves 1,4-difluoroalkylation, desulfonylation, cyclization, and dehydrated and dehydrofluorinated aromatization and represents the first application of difluoroenoxysilane in cascade transformations. Furthermore, this methodology is highlighted by the synthesis of three fluoro analogues of bioactive molecules with potent topoisomerase inhibitory activities.

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An efficient approach for the reversal of regioselectivity in the nucleophilic introduction of difluorinated carbanion into α,β-enones has been developed via a silylium catalysis. The strong electron-withdrawing properties and bulky substituents of in situ-generated silyl triflic imide catalyst is the key for the 1,4-addition reaction to proceed smoothly. The synthetic utility is highlighted by the further use of this method for the synthesis of 2,4,6-triarylsubstituted 3-fluoropyridines in a one-pot manner.

A catalytic and highly enantioselective Mukaiyama–Michael addition of difluoroenoxysilanes to azadienes has been developed using perfluorinated aryl-incorporating chiral monophosphoric acid (PF-CPA) as an effective, multipoint-controlled chiral catalyst. The inherent perfluoroaryl substituent is finely beneficial not only for achieving high catalytic activity but also for creating a compact and confined chiral environment for highly enantioselective transformations. Theoretical studies showed that the π–π interaction and hydrogen bond between PF-CPA and substrates play a crucial role in determining the stereochemical outcomes in comparison with those of phenyl, binaphthyl, and partially fluorinated aryls.

A multicomponent dearomative difluoroalkylation of isoquinolines has been developed with difluorinated silyl enol ethers serving as poor nucleophiles without an additional transition-metal or organic catalyst. The sequential oxidative rearomatization under different alkaline conditions provides a controllable formal C−H difluoroalkylation and difluoromethylation method for isoquinolines without peroxide or metal oxidant. A series of isoquinolines including a pharmaceutical, phenanthridine, quinolines, and difluorinated silyl enol ethers were suitable substrates to construct gem-difluorinated heterocycles. The inexpensive starting materials, mild reaction conditions, and simple operation also show practical and environmentally benign advantages.

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