Jinbo Hu

Synthesis of gem‐Difluorocyclopropa(e)nes and O‐, S‐, N‐, and P‐Difluoromethylated Compounds with TMSCF2Br

Two-in-one: Me3 SiCF2 Br is an efficient difluorocarbene source and is compatible with both neutral and aqueous basic conditions. Bromide-ion-initiated [2+1] cycloaddition with alkenes/alkynes and hydroxide ion promoted α-addition with (thio)phenols, (thio)alcohols, sulfinates, heterocyclic amines, and H-phosphine oxides give the corresponding gem-difluorinated compounds with broad functional-group tolerance.

Silver-mediated trifluoromethylation-iodination of arynes.

An unprecedented silver-mediated vicinal trifluoromethylation-iodination of arynes that quickly introduces CF(3) and I groups onto aromatic rings in a single step to give o-trifluoromethyl iodoarenes has been developed. A new reactivity of AgCF(3) has been revealed, and 2,2,6,6-tetramethylpiperidine plays an important role in this difunctionalization reaction.An unprecedented silver-mediated vicinal trifluoromethylation-iodination of arynes that quickly introduces CF3 and I groups onto aromatic rings in a single step to give o-trifluoromethyl iodoarenes has been developed. A new reactivity of AgCF3 has been re

Copper-catalyzed gem-difluoroolefination of diazo compounds with TMSCF3 via C-F bond cleavage.

A novel Cu-catalyzed gem-difluoroolefination of diazo compounds is described. This transformation starts from readily available TMSCF3 and diazo compounds, via trifluoromethylation followed by C-F bond cleavage, to afford the desired 1,1-difluoroalkene products.

Copper-Mediated Trifluoromethylthiolation of α-Diazoesters

A novel Cu-mediated trifluoromethylthiolation of diazo compounds has been developed that provides a convenient synthetic route for the efficient α-trifluoromethylthiolation of simple esters under mild reaction conditions. The reaction is typically carried out at room temperature, and water could be used to promote the reaction.

gem-Difluoroolefination of Diazo Compounds with TMSCF3 or TMSCF2Br: Transition-Metal-Free Cross-Coupling of Two Carbene Precursors

A new olefination protocol for transition-metal-free cross-coupling of two carbene fragments arising from two different sources, namely, a nonfluorinated carbene fragment resulting from a diazo compound and a difluorocarbene fragment derived from Ruppert-Prakash reagent (TMSCF3) or TMSCF2Br, has been developed. This gem-difluoroolefination proceeds through the direct nucleophilic addition of diazo compounds to difluorocarbene followed by elimination of N2. Compared to previously reported Cu-catalyzed gem-difluoroolefination of diazo compounds with TMSCF3, which possesses a narrow substrate scope due to a demanding requirement on the reactivity of diazo compounds and in-situ-generated CuCF3, this transition-metal-free protocol affords a general and efficient approach to various disubstituted 1,1-difluoroalkenes, including difluoroacrylates, diaryldifluoroolefins, as well as arylalkyldifluoroolefins. In view of the ready availability of diazo compounds and difluorocarbene reagents and versatile transformations of 1,1-difluoroalkenes, this new gem-difluoroolefination method is expected to find wide applications in organic synthesis.

AgF-mediated fluorinative cross-coupling of two olefins: facile access to α-CF3 alkenes and β-CF3 ketones.

A AgF-mediated fluorination with a concomitant cross-coupling between a gem-difluoroolefin and a non-fluorinated olefin is reported. This highly efficient method provides facile access to both α-CF3 alkenes and β-CF3 ketones, which otherwise remain challenging to be directly prepared. The application of this method is further demonstrated by the synthesis of bioactive isoxazoline derivatives. This approach represents a conceptually novel route to trifluoromethylated compounds that combines the inu2005situ generation of the CF3 moiety and a C-H functionalization in a single reaction system.

Fluoroalkylative Aryl Migration of Conjugated N-Arylsulfonylated Amides Using Easily Accessible Sodium Di- and Monofluoroalkanesulfinates

Fluorinated sulfinate salts RfSO2Na (Rf = CF2H, CF2Ph, and CH2F) have been prepared via NaBH4-mediated reduction of the corresponding benzo[d]thiazol-2-yl sulfones, and their synthetic application as di- and monofluoroalkyl radical precursors is demonstrated in the silver-catalyzed cascade fluoroalkylation/aryl migration/SO2 extrusion of conjugated N-arylsulfonylated amides.

Copper-mediated trifluoromethylation of propiolic acids: facile synthesis of α-trifluoromethyl ketones

Copper-mediated decarboxylative trifluoromethylation provides a new protocol for the efficient preparation of α-trifluoromethyl ketones from propiolic acids. It was found that water is involved as a reactant in the reaction, which is significantly different from the previously reported decarboxylative fluoroalkylation reactions.

AgF-mediated fluorinative homocoupling of gem-difluoroalkenes.

A novel silver(I)-fluoride-mediated homocoupling reaction of β,β-difluorostyrene derivatives is described. The transformation is initiated via nucleophilic addition of silver(I) fluoride to β,β-difluorostyrenes, which is followed by dimerization of the corresponding benzylsilver intermediates. The reaction shows good substrate scope, functional group tolerance, and represents the first report on the reactivity of (α-trifluoromethyl)benzylsilver species.

gem‐Difluoroolefination of Diaryl Ketones and Enolizable Aldehydes with Difluoromethyl 2‐Pyridyl Sulfone: New Insights into the Julia–Kocienski Reaction

The direct conversion of diaryl ketones and enolizable aliphatic aldehydes into gem-difluoroalkenes has been a long-standing challenge in organofluorine chemistry. Herein, we report efficient strategies to tackle this problem by using difluoromethyl 2-pyridyl sulfone as a general gem-difluoroolefination reagent. The gem-difluoroolefination of diaryl ketones proceeds by acid-promoted Smiles rearrangement of the carbinol intermediate; the gem-difluoroolefination is otherwise difficult to achieve through a conventional Julia-Kocienski olefination protocol under basic conditions due to the retro-aldol type decomposition of the key intermediate. Efficient gem-difluoroolefination of aliphatic aldehydes was achieved by the use of an amide base generated in situ (from CsF and tris(trimethylsilyl)amine), which diminishes the undesired enolization of aliphatic aldehydes and provides a powerful synthetic method for chemoselective gem-difluoroolefination of multi-carbonyl compounds. Our results provide new insights into the mechanistic understanding of the classical Julia-Kocienski reaction.