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Research has been conducted on tri- and difluoromethylsilanes. The authors describe the preparation of these compounds via the use of magnesium metal-mediated reductive tri- and difluoromethylation of chlorosilanes.

Owing to the excellent performance of fluorinated compounds in the areas of pharmaceuticals, agrochemicals, and materials chemistry, organic chemists have made great efforts towards the selective incorporation of fluorine or fluorinated moieties into organic molecules through nucleophilic, electrophilic, radical, and metal-catalyzed pathways. Impressive progress in fluorination and perfluoroalkylation (especially trifluoromethylation) reactions has been made over the past few decades. However, methods for incorporating lightly fluorinated groups (such as −CF2H) are still underdeveloped, in spite of their important applications in pharmaceuticals and agrochemicals. This Focus Review summarizes recent developments in metal-catalyzed direct difluoromethylation reactions. [ABSTRACT FROM AUTHOR]

A pentacoordinate bis(difluoromethyl)silicate anion, [Me3Si(CF2H)2]−, is observed for the first time by the activation of Me3SiCF2H with a nucleophilic alkali-metal salt and 18-crown-6. Further study on its reactivity by tuning the countercation effect led to the discovery and development of an efficient, catalytic nucleophilic difluoromethylation of enolizable ketones with Me3SiCF2H by using a combination of CsF and 18-crown-6 as the initiation system. Mechanistic investigations demonstrate that [(18-crown-6)Cs]+[Me3Si(CF2H)2]− is a key intermediate in this catalytic reaction. [ABSTRACT FROM AUTHOR]

A copper-mediated deuterotrifluoromethylation of α?diazo esters under the promotion of deuterium oxide (D2O) has been developed for the synthesis of deuterium-labeled trifluoromethyl compounds. This deuterotrifluoromethylation reaction is of broad scope and can afford the deuterated products with higher than 99% isotopic purity. Moreover, the results of this investigation also provide some experimental evidences to support our previously proposed trifluoromethylation mechanism. [ABSTRACT FROM AUTHOR]

A new method for the generation of the “PhSO2CF2Cu” species from readily available difluoromethyl phenyl sulfone (PhSO2CF2H) has been developed. The “PhSO2CF2Cu” reagent can be applied in (phenylsulfonyl)difluoromethylation of arylboronic acids, which affords a convenient approach to introducing the PhSO2CF2 group into aromatics. [ABSTRACT FROM AUTHOR]

Unlike the facile synthesis of β-monofluoromethyl alcohols by nucleophilic monofluoromethylation of epoxides, the synthesis of β-difluoromethyl alcohols by nucleophilic difluoromethylation of epoxides still remains a challenge. Herein, studies on tackling this problem with PhSO(NTBS)CF2H ( 2; TBS= tert-butyldimethylsilyl) are reported. The preorganization of 2 and epoxides with BF3 ⋅Et2O was found to be crucial for the reaction. The reaction shows excellent regioselectivity and has a broad substrate scope. The facile transformation of the ring-opened products to β-difluoromethyl, γ-difluoromethyl, and β-difluoromethylenyl alcohols demonstrates the synthetic utility of the reaction. [ABSTRACT FROM AUTHOR]

Although many methods are available for the synthesis of optically enriched monofluoromethyl secondary alcohols, synthesizing optically enriched monofluoromethyl tertiary alcohols remains a challenge. An efficient and easy-to-handle nucleophilic fluoromethylation protocol was developed. The current monofluoromethylation showed much higher facial selectivity than the corresponding difluoromethylation and proceeded via a different type of transition state. Excellent stereoselective control at the fluorinated carbon chiral center was found, an effect believed to be facilitated by the dynamic kinetic resolution of the chiral α-fluoro carbanions. [ABSTRACT FROM AUTHOR]

Zwei Reaktionswege: Me3SiCF2Br, eine effiziente Quelle für Difluorcarben, ist kompatibel mit neutralem und basischem wässrigem Milieu. Die durch Bromidionen ausgelöste [2+1] ‐ Cycloaddition mit Alkenen/Alkinen und die durch Hydroxidionen vermittelte α ‐ Addition an (Thio)Phenole, (Thio)Alkohole, Sulfinate, heterocyclische Amine und H ‐ Phosphinoxide ergeben gem ‐ difluorierte Produkte mit Toleranz für viele funktionelle Gruppen. [ABSTRACT FROM AUTHOR]

A new strategy for nucleophilic addition to aldehydes with difluoromethyl organometallic reagents has been developed by functionalizing the difluoromethyl moiety with the phenylsulfonyl group (SO 2 Ph). This electron-withdrawing group influences both the thermodynamic stability and the nucleophilicity of difluoromethyl organometallic reagents, which plays an important role in the nucleophilic difluoromethylation of aldehydes. [ABSTRACT FROM AUTHOR]

Abstract: Stereoselective free radical (phenylsulfonyl)difluoromethylation of terminal alkynes with iododifluoromethyl phenyl sulfone (PhSO2CF2I) has been accomplished by using Et3B/air as an initiator. The obtained PhSO2CF2-substituted vinyl iodides, which can be further subjected to Suzuki coupling and Sonogashira coupling reactions, are useful precursors for the preparation of many structurally diverse PhSO2CF2- and CF2H-substituted alkenes. [Copyright &y& Elsevier]

A new method forthe generation of trifluoromethylcopper (“CuCF3”)species from readily available phenyl trifluoromethylsulfoxide has been developed. The “CuCF3”reagent can be applied in efficient trifluoromethylations of aryliodides and activated aryl bromides in the absence of additional ligands.Furthermore, the “CuCF3” species can alsoundergo oxidative cross-coupling with terminal alkynes and arylboronicacids. [ABSTRACT FROM AUTHOR]

An efficient radical (2-pyridylsulfonyl)difluoromethylation of terminal alkenes with 2-PySO 2 CF 2 I has been successfully achieved by using catalytic amount of Et 3 B/air as initiating system. This methodology was also further extended to the synthesis of 2-PySO 2 CF 2 -substituted alkanes and alkenes. [ABSTRACT FROM AUTHOR]

Highlights: [•] The reactions between carbonyls and PhSO2CF2H have been accomplished using in situ generated substoichiometric amount of base. [•] A protocol for effective difluoro(phenylsulfonyl)methylation of enolizable aldehydes under basic conditions is developed. [•] The reactivity difference between PhSO2CF2H and CF3H toward carbonyls has been disclosed and rationalized. [ABSTRACT FROM AUTHOR]

Abstract: A protocol for the synthesis of difluoromethylated tertiary amines by nucleophilic difluoromethylation of N,N-acetals using TMSCF2SO2Ph reagent is developed. The reaction proceeds smoothly in 1,4-dioxane using K2CO3 as the initiator. A key feature of the reaction is that the in situ generated iminiums (from N,N-acetals and CF3COOH) could be fluoroalkylated in an efficient way. [Copyright &y& Elsevier]

Abstract: An efficient and straightforward nucleophilic difluoromethylation of Cn heterocycles under the activation of alkylating agents has been developed. Cyclic iminium salts derived from dihydroisoquinolines, quinolines, and pyridines were successfully difluoromethylated with sulfur-based fluoroalkyl silanes affording a series of new difluoromethylated nitrogen-containing heterocyclic compounds. [Copyright &y& Elsevier]

Abstract: A series of sulfur-, selenium- and tellurium-containing (phenylchalcogen)difluoromethylation reagents PhSCF2H (1a), PhSeCF2H (1b), and PhTeCF2H (1c) were prepared, and their relative reactivity towards aldehydes, ketones, and imines was investigated. Compared to the former developed (phenylchalcogen)difluoromethylation reagents, these reagents are relatively easily available and more atom-economical in fluoroalkylation reactions. It was found that the efficient nucleophilic (phenylchalcogen)difluoromethylation of aldehydes, ketones, and imines could be achieved with 1a–1c. Reagents 1a and 1b showed better reactivity than 1c toward carbonyl compounds and imines, and PhOCF2H (1d) was found to be unable to undergo similar fluoroalkylation reactions. [Copyright &y& Elsevier]

Abstract: We have investigated the different chlorodifluoromethyl aryl ketones 1a–1g and sulfones 2a–2h as difluorocarbene reagents for O- and N-difluoromethylations. It was found that the sulfone reagents 2 were generally more efficient in difluoromethylation than the ketone reagents 1. Furthermore, while the different substituents on ketone reagents 1 did not show a remarkable impact on the difluoromethylation reaction, the substituent effect on the sulfone reagents 2 was much more significant. Finally, we found that p-chlorophenyl chlorodifluoromethyl sulfone 2d and p-nitrophenyl chlorodifluoromethyl sulfone 2h were among the most powerful difluorocarbene reagents in this category for O-difluoromethylations. [Copyright &y& Elsevier]

Alkoxide-induced nucleophilic pentafluoroethylation and trifluoromethylation of aldehydes, ketones, and imines using pentafluoroethyl phenyl sulfone (PhSO2CF2CF3, 1) and trifluoromethyl phenyl sulfone (PhSO2CF3, 2), respectively, have been successfully achieved. High diastereoselectivity was observed during the perfluoroalkylation of homochiral sulfinimines to give the corresponding perfluoroalkyl sulfinamides. [ABSTRACT FROM AUTHOR]

The reagent 'PhSO2CF2Cu' is generated in the reaction from sulfone (I) and it further reacts with aryl- and heteroarylboronic acids to afford the desired products. [ABSTRACT FROM AUTHOR]

The advantages of the method are: (1) unactivated alkyl bromides can serve as substrates; (2) only slight excess of alkyl bromides is necessary. [ABSTRACT FROM AUTHOR]

The reaction proceeds with excellent stereocontrol at the chiral fluorinated carbon center, which is attributed to a dynamic kinetic resolution of the chiral α-fluoro carbanions. [ABSTRACT FROM AUTHOR]

Interestingly, in contrast to the previously known detrimental effect of an α-fluorine substitution on SN2 reactions, the presented monofluoromethylation is accelerated by the α-fluorine substitution. [ABSTRACT FROM AUTHOR]

Aliphatic as well as aromatic aldehydes undergo nucleophilic difluoro(phenylsulfonyl)methylation by reaction with PhSO2CF2H (I). [ABSTRACT FROM AUTHOR]

The reaction differs from the previously known decarboxylative trifluoromethylation protocols as water is involved as a reagent in the reaction. [ABSTRACT FROM AUTHOR]