Trifluoromethanesulfinate

The reactivity of triflate-substituted pyridopyrrolizines has been investigated. In the presence of a polar aprotic solvent and a nucleophile, these compounds undergo Sn reactions, leading to the a-substituted 3//-3-pyrrolones. This process is thought to involve loss of the trifluoromethanesulfinate ion, formation of an acyliminium ion intermediate, and nucleophilic attack on the latter <1995JOC5382> (Scheme 44). 

One-pot electrosynthesis of trifluoromethanesulfinic acid is also achieved at sacrificial anodes in good current efficiency Eq. 9) [23). 

Because of the usually high temperatures required to rearrange propargyl sulfi-nates to allenyl sulfones, a report about such palladium-catalyzed transformations seems to be promising [106], Even at low temperatures the synthesis and isomerization of trifluoromethanesulfinate 51 are possible if, during the reaction of the ter-... 

Conversion of CHNH2 to, C=0.2 A convenient three-step conversion of alkyl 6-aminopenicillanates (1) into 6-oxopenicillanates (3) involves ditrifluorometha-nesullonation to give a ditriflamide (2), which in the presence of base eliminates trifluoromethanesulfinic acid to form an imine (a). Hydrolysis of a to the ketone 3 is effected with dilute HC1. 

Primary and secondary trifluoromethylsulfones (triflones) such as 12 are efficiently obtained from readily available sodium trifluoromethanesulfinate (10) and alkyl bromides (e. g., 11) in A, A -dimethylacetamide (DMAC). Simple primary alkyl bromides may also be employed. 

More useful from a synthetic point of view than any of these variations is the discovery by Hendrickson that trifluoromethanesulfinate ( triflinate ) is a very effective leaving group in Ramberg-BScklund reactions. The reaction succeeds only if the precursors, a-triflyl sulfones, are fully substituted at the a-position if they are not, simple deprotonation occurs under the basic reaction conditions because the triflyl group is so strongly electron withdrawing. Consequently, this approach is applicable only to the syndesis of 1,1-di-, tri- and tetra-substituted alkenes. 

Intramolecular iminoacetonitrile [4-1-2] cycloaddition has been exploited in the synthesis of quinolizidine alkaloids (Scheme 54). The intermediate 187 was generated by elimination of trifluoromethanesulfinate from 188 and underwent the desired aza Diels-Alder reaction to give 189. A series of steps which included reduetive decyanation, alkylation with (Z)-3-bromo-l-chloropropene, classical resolution, and Sonogashira coupling provided the alkaloid (-)-217A 190<050L3115>. 

In a similar way, pyridine phosphonium salts and phosphonates can be prepared by reaction of trivalent phosphorus compounds with the more accessible iV-trifluoromethanesulfonyl-pyridinium salts, when tri-fluoromethanesulfone is the leaving group from nitrogen (as sulfinate anion) attack is normally at C-4, as illustrated below. The A -trifluoromethanesulfonyl-pyridinium salts also react with ketones or with electron-rich aromatic compounds to give 1,4-dihydropyridine adducts. Subsequent treatment with potassium t-butoxide brings about elimination of trifluoromethanesulfinic acid, and thus aromatisation. It is also possible to utilise phosphonates in reaction with aldehydes, leading finally to 4-substimted pyridines. ... 

This condensation with sulfur dioxide is rather peculiar. To the difference with carbonyl electrophiles, sulfur dioxide is more easily reduced than trifluoromethyl bromide. As already pointed out, initial consumption of zinc by this anhydride was obvious, producing the sulfoxylate radical anion which is known to be in equilibrium with the dithionite anion (Fig. 15). Incidentally, this salt mixed with sodium bicarbonate in aqueous acetonitrile was used for the transformation of liquid perhalogenoalkyl halides into their corresponding sulfmates (ref. 24). We have been able to transform the gaseous and poorly reactive trifluoromethyl bromide into sodium trifluoromethanesulfinate. However, the reaction conditions (Fig. 16) (ref. 25) were modified because no transformation occurred in the medium employed for the sulfinato-dehalogenation of the liquid halides. 

Fig. 16. Formation of sodium trifluoromethanesulfinate from sodium dithionite...

The relatively stable trifluoromethanesulfinic acid azide,14 synthesized from trifluoromethane-sulfinyl chloride and sodium azide, begins to decompose at — 10 C to give the extremely reactive sulfur oxide nitrene 4. The intermediate 4 oligomerizes spontaneously, but in the presence of acetonitrile compound 4 forms the stable dithiatriazine 1,3-dioxide 5. cis- and ri-mw-Isomers of compound 5 can be detected by gas chromatography (ratio 8 10). 

No reaction between trimethy](trifluoroniethyl)silane and sulfur dioxide occurs in the absence of an anionic initiator when one molar equivalent of tetrabutylammonium fluoride is used, clean formation of tetrabutylammonium trifluoromethanesulfinate is observed.112 Although oxidation to the corresponding sulfonate occurred readily upon treatment with 30% hydrogen peroxide, attempts to liberate the free acid from the salt proved unsuccessful. When sodium trimethylsilanolate was used as the initiator, however, the reaction sequence was successful. The overall yield of trifluoromethanesulfonic acid (31) was about 30%. 

The fourth modification, discovered by Hendrickson in 1985,17,18 uses triflinate (trifluoromethanesulfinate) in place of the halogen as the leaving group as depicted by 1819. 18 Similarly, Matsuyama used p-toluenesulfinate as the leaving group as... 

The trifluoromethanesulfinate salt thus obtained can be transformed to the sulfonyl chloride by chlorination and to the sulfonic acid by oxidation with hydrogen peroxide. 

In contrast to trifluoroacetate, the trifluoromethanesulfinate ion can be oxidized at a much less positive potential. Quite recently, Ignat ev and co-workers have found that anodic oxidation of sodium trifluoromethanesulfinate results in generation of the trifluoromethyl radical, which can be trapped by arenes and followed by reoxidation and deprotonation, provides trifluoromethylated arenes in ca. 50% yield as shown in Eq. 74. ... 

Nucleophilic attack of t-BuO anion on carbon, sulfur, or silicon conqiounds such as TMSCP3, 4 secondary trifluoroamides and trifluoroacetates, secondary trifluoromethanesulfinamides and trifluoromethanesulfinates, and trifluoromethyl sulfoxides and sulfones allows the transfer of a trifluoromethyl carbanion to various electrophilic acceptors, such as nonenolizable ketones and aldehydes (eq 54). ... 

Heteroarene Functionalization One-pot Sequential Functionalization Chemistry. Zinc isopropylsuUinate can be considered as a radical with nucleophilic character. Zinc trifluoromethanesulfinate (TFMS), another zinc bis(alkanesulfinate) reagent, possesses a rather electrophilic character. By taking advantage of the electrophiUcity/ nucleophiUcity of the reactive radical species, a one-pot sequential functionalization reaction was developed. Dihydroquinine can undergo tandem trifluoromethylation and isopropylation without the need for secondary alcohol protection (eq 7). 

Form Supplied in off-white powder. In its purest form, it is most likely a cUhydrate. When preparing zinc trifluoromethanesulfinate (TFMS), common impurities are Zn, ZnCl2, and H2O Zn... 

Introduction. Zinc trifluoromethanesulfinate (TFMS) is a commercially available reagent that appends trifluoromethyl units to heteroarenes under practical and mild conditions. Reaction temperatures range between room temperature (rt) and 50 °C, the reaction is tolerant of air and moisture, and the reaction solvent can be H2O or even unconventional media such as tea or cell lysate. Innately reactive positions of a heteroarene undergo the transformation of carbon-hydrogen to carbon-trifluoromethyl. C-H functionalization of innate positions and methods to override this inherent reactivity, as well as one-pot sequential functionalizations of two different positions of a heteroarene will be discussed herein. 

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