1608-24-8

Upstream product

• 75-61-6 dibromodifluoromethane 
• 5953-85-5 p-anisaldehyde hydrazone 
• 1219454-89-3 2-((difluoromethyl)sulfonyl)pyridine 
• 123-11-5 4-methoxy-benzaldehyde 
• 104-92-7 1-bromo-4-methoxy-benzene 
• 5720-07-0 4-methoxyphenylboronic acid 
• 2236129-81-8 trifluoroacetaldehyde N-triftosylhydrazone 
• 87189-16-0 potassium 2-bromo-2,2-difluoroacetate 
• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 939-97-9 4-tert-Butylbenzaldehyde 
• 1530-38-7 ((4-methoxyphenyl)methyl)triphenylphosphonium bromide 
• 21960-26-9 (4-methoxybenzylidene)triphenylphosphorane 
• 1535-65-5 difluoromethyl phenyl sulfone 
• 371-67-5 2,2,2-trifluorodiazoethane 

Downstream Products

• 130537-03-0 (E)-2-fluoro-3-(4-methoxyphenyl)acrylonitrile 
• 637-69-4 4-Methoxystyrene 
• 15197-86-1 1-(2-fluorovinyl)-4-methoxybenzene 
• 26928-26-7 (Z)-1-Fluoro-2-(4-methoxyphenyl)ethylene 

Relevant academic research and scientific papers

Novel 2,2-difluorovinylzirconocene: A facile synthesis of monosubstituted gem-difluoroolefins via its cross-coupling reaction

2,2-Difluorovinyl p-toluenesulfonate, readily obtained from 2,2,2-trifluoroethanol, is treated with zirconocene equivalent 'Cp2Zr' to generate the remarkably thermostable nonsubstituted 2,2-difluorovinylzirconocene, which in turn couples with a

Wittig gem-difluoroolefination of aldehydes with difluoromethyltriphenylphosphonium bromide

Wittig reaction of aldehydes with difluoromethyltriphenylphosphonium bromide leading to gem-difluoroolefins in moderate yields is described. The reaction displays a good substrate scope including aryl, heteroaryl and α,β-unsaturated aldehydes. Difluoromethyltriphenylphosphonium bromide could be easily prepared and stored for a long time under air atmosphere. The salt exhibits high thermal stability demonstrated by thermogravimetric analysis. Its structure was confirmed by NMR spectroscopy and single crystal X-ray analysis.

Stereoselective formation of Z-monofluoroalkenes by nickel-catalyzed defluorinative coupling of gem?difluoroalkenes with lithium organoborates

A method for stereoselective construction of Z-monofluoroalkenes by nickel-catalyzed defluorinative coupling of gem?difluoroalkenes in mild conditions was described. The combination of lithium organoborate and ZnBr2 generated in situ lithium ar

Difunctionalization of gem-Difluoroalkenes via Photoredox Catalysis: Synthesis of Diverse α,α-Difluoromethyl-β-alkoxysulfones

Visible-light-promoted alkoxysulfonylation of gem-difluoroalkenes using sulfonyl chlorides and alcohols has been developed. The reaction exhibits a relatively broad substrate scope with excellent functional group compatibility. This synthesis method includes an atom transfer radical addition-like process. The products can be used as platform molecules for further modification.

Fluoride-Triggered Synthesis of 1-Aryl-2,2-difluoroalkenes via Desilylative Defluorination of (1-Aryl)-2,2,2-trifluoroethyl-silanes

An efficient route for the synthesis of 1-aryl-2,2-difluoroalkenes via 1,2-desilylative defluorination is disclosed. Only a catalytic amount of fluoride source is required to initiate the desilylation and afford gem-difluoroalkenes in very good to quantitative yields, using mild reaction conditions in dimethyl carbonate as a green solvent. This reaction uses (1-aryl)-2,2,2-trifluoroethyl-silanes, which are easily prepared via the insertion reaction of trifluoroethyl diazo alkanes into the Si-H bond of tertiary organosilanes. (1-Aryl)-perfluoroalkyl-silanes cleanly afford the corresponding (Z)-1-benzylideneperfluoroalkanes, which upon hydrodefluorination furnish the (E)-β(perfluoroalkyl)styrene derivatives with excellent yield and complete stereoselectivity. A one-pot system involving sequential insertion and desilylative-defluorination is also suitable for this transformation. This method demonstrates the usefulness of organosilanes toward the preparation of fluorinated alkenes as synthetically useful targets.

Acid-Catalyzed Hydrothiolation of gem-Difluorostyrenes to Access α,α-Difluoroalkylthioethers

The substitution of hydrogen atoms with fluorine in bioactive molecules can greatly impact physicochemical, pharmacokinetic, and pharmacodynamic properties. However, current synthetic methods cannot readily access many fluorinated motifs, which impedes utilization of these groups. Thus, the development of new methods to introduce fluorinated functional groups is critical for developing the next generation of biological probes and therapeutic agents. The synthesis of one such substructure, the α,α-difluoroalkylthioether, typically requires specialized conditions that necessitate early-stage installation. A late-stage and convergent approach to access α,α-difluoroalkylthioethers could involve nucleophilic addition of thiols across gem-difluorostyrenes. Unfortunately, under basic conditions, nucleophilic addition to gem-difluorostyrenes generates an anionic intermediate that can undergo facile elimination of fluoride to generate α-fluorovinylthioethers. To overcome this decomposition, we herein exploit an acid-based catalyst system to facilitate simultaneous nucleophilic addition and protonation of the unstable intermediate. Ultimately, the optimized mild conditions afford the desired α,α-difluoroalkylthioethers in high selectivity and moderate to excellent yields. These α,α-difluoroalkylthioethers are less nucleophilic and more oxidatively stable relative to nonfluorinated thioethers, suggesting the potential application of this unexplored functional group in biological probes and therapeutic agents.

Stereoselective Synthesis of Difluorinated 1,3-Dienes via Palladium-Catalyzed C-F Bond Activation of Tetrasubstituted gem-Difluoroalkenes

A highly diastereoselective Pd(0)-catalyzed synthesis of difluorinated 1,3-dienes is described. Symmetrical 1,3-dienes containing a vicinal difluoro moiety can be obtained as single diastereomers from tetrasubstituted gem-difluoroalkenes. The reaction presumably proceeds through a stereoselective twofold Pd-catalyzed Miyaura borylation/Suzuki-Miyaura cross-coupling of the C-F bond. Moreover, modular synthesis of unsymmetrical difluorinated 1,3-dienes is also achievable by the coupling between gem-difluoroalkenes and borylated monofluoroalkenes.

Iron-Catalyzed Regioselective Alkenylboration of Olefins

The first examples of an iron-catalyzed three-component synthesis of homoallylic boronates from regioselective union of bis(pinacolato)diboron, an alkenyl halide (bromide, chloride or fluoride), and an olefin are disclosed. Products that bear tertiary or quaternary carbon centers could be generated in up to 87 % yield as single regioisomers with complete retention of the olefin stereochemistry. With cyclopropylidene-containing substrates, ring cleavage leading to trisubstituted E-alkenylboronates were selectively obtained. Mechanistic studies revealed reaction attributes that are distinct from previously reported alkene carboboration pathways.

Dehalogenative Cross-Coupling of gem-Difluoroalkenes with Alkyl Halides via a Silyl Radical-Mediated Process

Herein, we describe a convenient general protocol for monofluoroalkenylation reactions of alkyl bromides involving cooperative visible-light photoredox catalysis and halogen abstraction. Mechanistic experiments showed that the products were generated by selective cross-coupling of aliphatic radicals with fluoroalkenyl radicals. Silyl radical-mediated halogen abstraction enabled the protocol to be used for the monofluoroalkenylation of a broad range of alkyl and heteroaryl halides. The protocol could be carried out on a gram scale and was applied to cholesterol, indicating its utility for late-stage monofluoroalkenylation reactions.

Design and Synthesis of TY-Phos and Application in Palladium-Catalyzed Enantioselective Fluoroarylation of gem-Difluoroalkenes

The first example of highly enantioselective fluoroarylation of gem-difluoroalkenes with aryl halides is presented by using a new chiral sulfinamide phosphine (Sadphos) type ligand TY-Phos. N-Me-TY-Phos can be easily synthesized on a gram scale from readily available starting materials in three steps. Salient features of this work including readily available starting materials, good yields, high enantioselectivities as well as broad substrate scope make this approach very practical and attractive. Notably, the asymmetric synthesis of an analogue of a biologically active molecule is also reported.