Gem-difluoromethylene Compounds Research Articles

Addition of Carboxylic Acids to gem-Difluoroalkenes for the Synthesis of gem-Difluoromethylenated Compounds.

We herein describe a straightforward protocol for the synthesis of carboxylic esters containing a gem-difluoromethylene unit. Readily available carboxylic acids can act as nucleophiles to add regioselectively to tetrasubstituted or trisubstituted β,β-difluoroacrylates (formal hydroacetoxylation) for the construction of RCO2-CF2 bonds. Thermal conditions are sufficient without the use of catalysts or additives.

Synthesis of Chiral gem-Difluoromethylene Compounds by Enantioselective Ethoxycarbonyldifluoromethylation of MBH Fluorides via Silicon-Assisted C-F Bond Activation.

The enantioselective ethoxycarbonyldifluoromethylation of Morita-Baylis-Hillman (MBH) fluorides with Me3SiCF2CO2Et under organocatalysis is described. Moderately functionalized chiral gem-difluoromethylene compounds with a stereogenic "C-CF2-C*" unit were synthesized in high yields with high enantioselectivities. The initial C-F bond activation is assisted by the silicon atom via a dual SN2'-SN2' stepwise pathway. Dynamic kinetic resolution of the MBH-fluorides explained the high yields and high ee's of the products. The method was extended to the enantioselective introduction of "Het-CF2" units.

Synthesis of gem-Difluoromethylenated Compounds Employing α,α-Difluoro-α-phenylsulfanyl-α-trimethylsilylmethane (PhSCF2SiMe3) as a gem-Difluoromethylene Building Block

α,α-Difluoro-α-phenylsulfanyl-α-trimethylsilylmethane (PhSCF2SiMe3) is a synthetically important fluorinating reagent. This account summarizes our work on the synthetic utility of α,α-difluoro-α-phenylsulfanyl-α-trimethylsilylmethane as a versatile gem-difluoromethylene building block for the preparation of a variety of gem-difluoromethylenated compounds. 1 Introduction 2 Fluoride-Catalyzed Nucleophilic Addition of PhSCF2SiMe3 to Carbonyl Compounds 2.1 Synthesis of gem-Difluoromethyl Aryl Ketones 2.2 Synthesis of gem-1,1-Difluoroalkenes 2.3 Synthesis of gem-Difluoromethylenated Cyclopentanol Derivatives 3 Fluoride-Catalyzed Nucleophilic Addition of PhSCF2SiMe3 to N-Substituted Phthalimides and Succinimide Derivatives 3.1 Synthesis of gem-Difluoromethylenated 1-Azabicyclic Compounds 3.2 Asymmetric Synthesis of gem-Difluoromethylenated Pyrrolizidines and Indolizidines 4 Fluoride-Catalyzed Nucleophilic Addition of PhSCF2SiMe3 to Anhydride Derivatives 5 Fluoride-Catalyzed Chemoselective Nucleophilic Addition of PhSCF2SiMe3 to Keto Esters 5.1 Synthesis of gem-Difluoromethylenated Spiro-γ-butyrolactones 5.2 Synthesis of gem-Difluoromethylenated Bicyclo[m.n.0]-alkan-1-ols and Their Ring-Expansion into gem-Difluoromethylenated Macrocyclic Lactones 6 Asymmetric Synthesis of 3,3-Difluoro-2-propanoylbicy­clo[3.3.0]octanes 7 Conclusions

Designer HF-based fluorination reagent: highly regioselective synthesis of fluoroalkenes and gem-difluoromethylene compounds from alkynes.

Hydrogen fluoride (HF) and selected nonbasic and weakly coordinating (toward cationic metal) hydrogen-bond acceptors (e.g., DMPU) can form stable complexes through hydrogen bonding. The DMPU/HF complex is a new nucleophilic fluorination reagent that has high acidity and is compatible with cationic metal catalysts. The gold-catalyzed mono- and dihydrofluorination of alkynes using the DMPU/HF complex yields synthetically important fluoroalkenes and gem-difluoromethlylene compounds regioselectively.

Iron-Catalyzed Cross-Coupling Reactions between Arylzinc Reagents and Alkyl Halides Bearing β-Fluorines

We report the first example of iron-catalyzed cross-coupling of α-halo-β,β-difluoroethylene-containing compounds with arylzinc reagents using TMEDA and dppp as coligands. The reaction affords a wide range of functional group tolerant gem-difluoromethylenated compounds in moderate to good yields. The facile dehalodefluorination of α-halo-β,β-difluoroethylene-containing compounds upon treatment of reductive metal reagents was mostly inhibited. Mechanistic studies indicated that the cross-coupling reaction could involve a single-electron-transfer process.

A cascade process for the synthesis of gem-difluoromethylene compounds

An efficient strategy for the synthesis of 2,2-difluoro-2,3-dihydrofuran derivatives from β-fluoroalkyl-β-enaminoketones is described. The reaction occurred via an intramolecular halophilic attack-initiated cascade process. A series of 2,3-dihydrofurans were prepared in high yields. And an intermolecular domino process achieved providing polysubstituted furans. The mechanism of the reaction is discussed.

Phenyl trifluorovinyl sulfide: a radical acceptor for preparation of gem-difluoromethylene compounds

Phenyl trifluorovinyl sulfide was prepared from the reaction of trifluorovinyllithium and S-phenyl benzenethiosulfonate. The fluorinated olefin showed reactivity with alkyl radicals generated from halogen-abstraction from alkyl halides. Reactions with alkyl halides required tris(trimethylsilyl)silane as a chain transfer reagent to improve selectivity of the products. Initiation of radical reaction was effected by thermal decomposition of AIBN. Oxidation of the thioether products gave the corresponding sulfoxides, which were successively converted into α,α-difluoroalkanecarboxylic acid thiol esters by Pummerer reaction.

Electrolytic partial fluorination of organic compounds: Part 44. Anodic gem-difluorodesulfurization using triarylamine mediators

Indirect anodic gem-difluorodesulfurization of dithioacetals was successfully carried out using triarylamine mediators to provide gem-difluoromethylene compounds in moderate to good yields.

The conversion of diaryl-1,3-dithiolanes into gem-difluoromethylene compounds by a combination of elemental fluorine and iodine

Diaryl-1,3-dithiolanes are converted to Gem-difluorides in good yield by reation with a mixture of elemental fluorine and iodine in acetonitrile at room temperature.