Trifluoromethyl Trimethylsilane Research Articles

Synthesis of CF3-Substituted Sulfoximines from Sulfonimidoyl Fluorides

N-Protected trifluoromethyl-substituted sulfoximines have been prepared by treatment of sulfonimidoyl fluorides with a combination of the Ruppert-Prakash reagent (TMSCF(3)) and tetrabutyl ammonium fluoride (TBAF). The starting materials were accessed following two synthetic routes, and for each reaction sequence the substrate scope was evaluated. Accordingly, a wide variety of aryl-substituted products were obtained in moderate to good yield.

Nucleophilic Trifluoromethylation of C=N Bonds

AbstractThe review covers nucleophilic addition reactions of the CF3 carbanion to C=N bonds. Trifluoromethylation reactions of imines, nitrones, hydrazones, iminium ions and azomethine ylides are discussed. Various trifluorometylating reagents are considered, among which the major emphasis is placed on reactions using the Ruppert–Prakash reagent.

The reaction of cyclic imines with the Ruppert–Prakash reagent. Facile approach to α-trifluoromethylated nornicotine, anabazine, and homoanabazine

We have demonstrated that the Ruppert–Prakash reagent is able to react with a number of cyclic imines under acidic condition to afford the corresponding α-trifluoromethyl derivatives of nitrogen heterocycles. 5–7-Membered cyclic imines bearing various alkyl, aryl or heterocyclic group were successfully involved in this transformation. Novel trifluoromethylated analogues of nicotine, anabasine, and homoanabasine alkaloids were synthesized.

Togni Reagent: A Hypervalent Iodine Based Electrophilic Trifluoromethylation Reagent

Antonio Togni and co-workers have [¹] reported a new electrophilic trifluoromethylating reagent based on a 10-I-3 hypervalent iodine, 3,3-dimethyl-1-(trifluoromethyl)-1,2-benziodoxole known as Togni reagent 1, which nicely complements the nucleophilic Ruppert-Prakash reagent. [²] The Togni reagent has the ability to transfer a CF3 moiety electophilically to a wide range of substrates and functionalities, including C=C and C-H bonds in hydrocarbons as well as atoms containing lone pairs, such as sulfide, primary and secondary alcohols. This electrophilic CF3 transfer agent is the reagent of choice for most trifluoro­methylation reactions (better than Yagupol’skii, [³] Umemoto, [4-8] and Shreeve [9] reagents) due to its substrate-induced selectivity, specificity, high reactivity under mild conditions (at 0-25 ˚C and neutral pH), and applicability to acid- or base-sensitive substrates. It is easy to handle and can be exposed to moist air for short periods of time without any apparent alteration.

Synthesis of Three‐, Five‐, and Six‐Membered Heterocycles Derived from New β‐Amino‐α‐(trifluoromethyl) Alcohols

AbstractNucleophilic trifluoromethylation of α‐imino ketones 2, derived from arylglyoxal, with Ruppert–Prakash reagent (CF3SiMe3) offers a convenient access to the corresponding O‐silylated β‐imino‐α‐(trifluoromethyl) alcohols. In a ‘one‐pot’ procedure, by treatment with NaBH4, these products smoothly undergo reduction and desilylation yielding the expected β‐amino‐α‐(trifluoromethyl) alcohols 4. The latter were used as starting materials for the synthesis of diverse trifluoromethylated heterocycles, including aziridines 5, 1,3‐oxazolidines 8, 1,3‐oxazolidin‐2‐ones 9, 1,3,2‐oxazaphospholidine 2‐oxides 10, 1,2,3‐oxathiazolidine 2‐oxides 11, and morpholine‐2,3‐diones 12. An optically active 5‐(trifluoromethyl)‐substituted 1,3‐oxazolidin‐2‐one 9g was also obtained.

ChemInform Abstract: Trifluoromethylation and Pentafluorophenylation of Sulfur and Carbon Centers Using (Trifluoromethyl)- and (Pentafluorophenyl) trimethylsilane.

Trifluoromethyl and pentafluorophenyl moieites are easily transferred to a variety of florinated inorganic and organic sulfur and carbon centers by using (trifluoromethyl)trimethylsilane and (pentafluorophenyl)trimethylsilane in the presence of catalytic a of fluoride ion. This methodology is readily applied to the simple, efficient preparation of known, previously difficult to obtain molecules, as well as a number of new perfluoroalkyl and perfluoroaryl sulfuranes, sulfoxides, ketones, esters, and alcohols

ChemInform Abstract: Synthesis of Trifluoromethyl Selenides

Alkyl and aryl trifluoromethylselenides are easily obtained from trifluoromethyl trimethylsilane and diselenides or selenocyanates as well as from sodium trifluoromethanesulfinate and diselenides or selenenyl chlorides, via trifluoromethaneselenosulfonates.

ChemInform Abstract: One-Pot Synthesis of N-Protected Amino Trifluoromethyl Ketones as Hydrated Hydrochloride Salts via the CsF-Catalyzed Reactions of (Trifluoromethyl)trimethylsilane with N-Protected Amino Esters.

ChemInform Abstract: One-Pot Synthesis of N-Protected Amino Trifluoromethyl Ketones as Hydrated Hydrochloride Salts via the CsF-Catalyzed Reactions of (Trifluoromethyl)trimethylsilane with N-Protected Amino Esters.

Enantiodivergent Approach to Trifluoromethylated Amines: A Concise Route to Both Enantiomeric Analogues of Calcimimetic NPS R‐568

AbstractReported herein is a straightforward and enantiodivergent synthesis of both enantiomers of trifluoromethylated analogues of calcimimetic NPS R‐569 in a highly estereoselective manner. The synthesis features a diastereoselective synthesis of the N‐(isopropylsulfinyl)imine unit by the “DAG methodology” and a diastereoselective addition of Ruppert–Prakash's reagent to the imine as the key steps. No protecting groups were necessary, permitting an atom economic synthesis in only six steps. Further addition reactions of the CF3 anion to different N‐(isopropylsulfinyl)imines were performed to demonstrate the suitability of the sulfinyl substituent to balance perfectly reactivity and diastereoselectivity.

Development of fluorination methods using continuous-flow microreactors

The safe and reliable use of various fluorination methods including nucleophilic fluorination (DAST), trifluoromethylation (Ruppert's reagent) and electrophilic fluorination (Selectfluor ®) in a continuous-flow microreactor is reported. Special attention was given to the use of in-line scavenging procedures in order to obtain clean products without the need for further purification.

Reaction of the Ruppert–Prakash reagent with perfluorosulfonic acids

A new property of Me 3SiCF 3 to undergo C–F bond activation upon interaction with perfluorosulfonic acids is described. The reaction is catalyzed by titanium tetrachloride and affords difluoromethyl perfluorosulfonates in good yields.

α-Trifluoromethylated Carbanion Synthons

Trifluomethylated organic compounds often have properties that make them suitable for diverse applications, including materials science, agrochemistry, and pharmaceutical industry. But of all the therapeutic drugs currently available, about 10% of them have a partially fluorinated moiety. Thus, a great deal of attention is being paid to the development of reliable methodologies for trifluoromethylation. Introduction of a trifluoromethyl group into the target molecules mostly relies on either trifluoromethylating reagents or trifluoromethylated synthetic blocks. The chemistry of trifluoromethyl carbanions, nucleophilic trifluoromethylating agents such as the Ruppert-Prakash reagent, and organometallic species has been intensively developed for their important synthetic applications. But the chemistry of beta,beta,beta-trifluoroethyl carbanions (alpha-trifluoromethyl carbanions) and organometallic species has remained undeveloped despite their potential usefulness in organic synthesis. The issue needs to be addressed. This Account outlines successful alkylations and useful synthetic applications of alpha-trifluoromethyl carbanions, such as alpha-substituted beta,beta,beta-trifluoroethyl, alpha-trifluoromethylethenyl, trifluoroacetimidoyl, alpha-trifluoromethyloxiranyl, and related alpha-trifluoromethylated carbanions. The strong electron-withdrawing effect of the alpha-trifluoromethyl group may stabilize the carbanion species electronically. But alpha-trifluoromethyl carbanions and their corresponding organometallic species mostly release fluoride spontaneously to produce difluoroalkenes. This notorious decomposition of alpha-trifluoromethylated carbanions and anionoids has hindered the development of these species for organic synthesis. A well-designed device for the generation, stabilization, and acceleration for alkylation of the alpha-trifluoromethylated carbanions is needed for their synthetic application, as well as stabilization by the electron-withdrawing alpha-substituent. The reported alpha-substituted alpha-trifluoromethyl carbanions can be roughly categorized into three classes based on their structures. The first category, A, is pi-conjugation-stabilized carbanions, which are stabilized by ester, nitro, sulfone, carbonyl, or phenyl groups. alpha-Substituents of these carbanions can delocalize the negative charges on their pi-system with large sigma R electron-withdrawing effects; this prevents accumulation of negative charge on the fluorine atoms. The second category, B, consists of carbanions with sp(3) orbitals either of highly halogenated carbanionsexamples include pentafluoroethyl(trimethyl)fluorosilicate, pentafluoroethyllithium, and alpha,alpha-dichloro-beta,beta,beta-trifluoroethylzinc speciesor of cyclic structures such as oxiranyl- and aziridinyllithiums. Both of these carbanions are also stabilized since they reduce molecular orbital (MO) overlapping of the carbanion orbital to C-F bond orbitals. The third category, C, has carbanions with their anion center at the sp(2) orbital, such as alpha-trifluoromethylated alkenyl carbanions and imidoyl carbanions. These sp(2) orbitals of the carbanion center usually have a small overlap with the C-F bonds of trifluoromethyl groups. The small overlap is able to suppress the E2-type eliminations. alpha-Trifluoromethylated carbanions are, in general, unstable. Their stability is largely affected by factors like hybridization of the orbital that accommodates lone pair electrons, the electronic nature of the alpha-substituents, the degree of covalency in a bond between the carbon and metal, the class of countercation, stabilization by chelation of a metal cation, and so on. The stability, therefore, can be sometimes controlled by tuning these factors adequately so that they can be used for organic synthesis. The chemistry of alpha-trifluoromethylated carbanions for organic synthesis has been progressing steadily. However, the simplest trifluoroethyl and trifluoroacetyl carbanions have never been successfully produced and employed for organic synthesis. Elegant generation and synthetic application of these metal species are one of the most attractive and challenging subjects for active investigation in the future.

Cinchona Alkaloids/TMAF Combination-Catalyzed Nucleophilic Enantioselective Trifluoromethylation of Aryl Ketones

The catalytic, nucleophilic enantioselective trifluoromethylation reaction of both acyclic and cyclic aryl ketones using the Ruppert-Prakash reagent is now at hand, with an operationally simple procedure, based on the combination of ammonium bromide of cinchona alkaloids with TMAF. The procedure is reliable and general. Trifluoromethyl-substituted tetrasubstituted aryl alcohols have been synthesized in up to 94% ee.

Preparation of Tri‐ and Difluoromethylated Amines from Aldimines Using (Trifluoromethyl)trimethylsilane.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Tri‐tert‐butylphosphine Is an Efficient Promoter for the Trifluoromethylation Reactions of Aldehydes, Ketones, Imides and Imines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Trifluoromethylation of Carbonyl Compounds with Trifluoromethyltrimethylsilane (Ruppert Reagent) Promoted by Triphenyldifluorostannates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Gas Phase Structure of Ruppert's Reagent, CF3SiMe3

CF3SiMe3 (Ruppert's reagent) has been investigated by gas phase electron diffraction, microwave spectroscopy and quantum chemical methods, deriving structural parameters and the barrier height for the methyl torsion. The bond length of the Si-CF3 bond, 1.941(3) A, is the longest Si-C bond observed so far in the gas phase. The V3 barrier for the methyl group torsion (V3= 5.71 kJ/mol) is only slightly lower than barriers determined for other trimethylsilane compounds.

Oxidative nucleophilic substitution of hydrogen in nitroarenes with trifluoromethyl carbanions. Synthesis of trifluoromethyl phenols

Trifluoromethyl carbanions generated from the Ruppert reagent and TASF add to highly electron-deficient nitroarenes to produce σH adducts subsequently oxidized with dimethyldioxirane to substituted trifluoromethyl phenols.

Oxidative nucleophilic substitution of hydrogen in nitroarenes with trifluoromethyl carbanions. Synthesis of trifluoromethyl phenols

Trifluoromethyl carbanions generated from the Ruppert reagent and TASF add to highly electron-deficient nitroarenes to produce σ H adducts subsequently oxidized with dimethyldioxirane to substituted trifluoromethyl phenols.

Improved Synthesis of Potassium (Trifluoromethyl)trifluoroborate [K(CF3BF3)

An improved synthesis of potassium (trifluoromethyl)trifluoroborate [K(CF3BF3)] has been developed. Thus Ruppert's reagent, (trifluoromethyl)trimethylsilane, is treated with trimethoxyborane in the presence of potassium fluoride. Aqueous hydrogen fluoride is added to the resulting intermediate, and the title compound can be isolated in 85% overall yield. The process is readily scalable, allowing a viable procedure for the synthesis of this potentially valuable reagent.