Methyl trifluoromethyl sulfide

Bis(trifluoromethyl) sulfoxide has been prepared1 previously by the direct fluorination of bis(trifluoromethyl) sulfide at —78°C. in hexafluoroethane followed by hydrolysis of the bis(trifluoro-methyl)sulfur difluoride (difluorobis(trifluoromethyl)sulfur). This method suffers because elemental fluorine must be used, and the yields are low. 

The oxidation of organic compounds with dioxirane reagents has emerged as an important synthetic method [93,94,95]. The effective use of dimethyldioxirane and methyl(trifluoromethyl)dioxirane for the mild and efficient oxidation of olefins, sulfides, amines, and saturated hydrocarbons naturally raised the question whether chiral versions of these reagents can be developed. 

Chloro-1 -methyl-3-trifluoromethyl- //-[ 1,3,4]oxadiazmo[5,6-fc]quinoxaline (570) suffered thiolytic ring fission in refluxing pyridine (containing phosphorus penta-sulfide) during 1 h to provide 7-chloro-3-[7/-methyl-A( -(triiluoroacetyl)hydrazino]-2(17/)-quinoxalinethione (571) in 87% yield. ... 

Hydrolysis is probably a more complex process, since 3,4-bis(trifluoro-methyl)perfluorohexa-2,4-diene gives a cyclic product—perfluorotetra-methylfuran 46 (94JCS(P1)3119, 90JCS(CC)1127). The reaction involves vinyl substitution of fluorine with subsequent fast electrocyclization of the intermediate carbanion accompanied by fluoride ion elimination. An analogous reaction of 3,4-bis(trifluoromethyl)perfluorohexa-2,4-diene with sodium sulfide or thiourea forms perfluorotetramethylthiophene 47 (90JCS(CC)1127). 

Based on the above discussion it was thought that the trifluoro-methyl ketones would be more polarized and thus create a great electrophilicity on the carbonyl carbon which facilitates -OH attack by the serine residue. Yet there is no carbon-oxygen bond to be cleaved In the ketone moiety, and therefore the enzyme-trifluoromethyl ketone transition state complex does not undergo catalytic conversion. The above rationale seems reasonable as trifluoromethyl ketones were found to be extraordinary selective and potent inhibitors of cholinesterases (56) of JHE from T. ni (57) and of meperidine carboxylesterases from mouse and human livers (58). Since JH homologs are alpha-beta unsaturated esters, a sulfide bond was placed beta to the carbonyl in hopes that it would mimic the 2,3-olefln of JHs and yield more powerful inhibitors (54). This empirical approach was extremely successful since it resulted in compounds that were extremely potent inhibitors of JHEs from different species (51,54,59). 

Trimethyl(trifluoromethyl)silane can be converted into tributyl(trifluoromethyl)tin (40) in quantitative yield by treatment with bis(tributyltin) oxide in tetrahydrofuran under fluoride ion initiation. Tributyl(trifluoromethyl)tin readily trifluoromethylates disilyl sulfides at room temperature giving the corresponding trifluoromethylated di- and trialkylsilancs 41 in high yields. This method provides a new approach for the preparation of silicon-based trifluoro-methylating reagents via transtrifluoromethylation of compounds containing Si — S bonds. 

Thermal and Lewis acid catalyzed ene reactions of electron-deficient ketones proceed in good yield. Dialkyl oxomalonate esters " and pyruvate esters have been most extensively studied. 1,2,3-Tri-ketones, methyl phenylglyoxylate, carbonyl sulfide, carbonyl cyanide, hexafluoroacetone, hexafluorocyclobutanone and 1,1,1-trifluoromethyl ketones have also been developed as enophiles. 

Trifluoromethyl aryl sulfides. The preparation of these substances from aryl halides requires a Cu(I)-catalyzed reaction with sulfur and methyl fluorosulfonyldi-fluoroacetate in HMPA or A(-methylpyrrolidinone. 

The similar alkoxide- or hydroxide-induced trifluoromethylation was also found to work with other electrophiles. Diphenyl disulfide can be trifluoromethylated to give trifluoromethyl phenyl sulfide in 87% yield (eq 4). Methyl benzoate can be trifluoromethylated to generate 2,2,2-trifluoroacetophenone in 30% yield at temperatures between —50°C and —20°C. Trifluo-romethylcopper (CF3CU) can be generated in situ with trifluoromethyl sulfone, f-BuOK, and copper iodide (Cul), and it then further reacts with iodobenzene at 80 °C for 20 h to give a,a,a-trifluorotoluene in 26% 3neld. ... 

Bis(triphenyltin)dihydridobis(methyldiphenylphosphine)plati-num, see Sn-00474 Bis(triphenyltin)oxide, see Sn-00440 >Bis(triphenyltin) sulfide, Sn-00443 Bis(triphenyltin)telluride, Sn-00446 >Bis(tripropyltin) oxide, see Sn-00339 >Bis[tris(2-methyl-2-phenylpropyl)tin] oxide, see Sn-00473 Bis[tris(pentafluorophenyl)germyl]cadmium, Ge-00271 Bis[tris(pentafluorophenyl)germyl] mercury, Ge-00273 Bis[tris(pentafluorophenyl)germyl] selenide, see Ge-00275 Bis[tris(pentafluorophenyl)germyl] sulfide, see Ge-00274 [Bis[tris(pentafluorophenyl)stannyl]]mercury, Sn-00435 Bis[tris(trifluoromethyl)germanium]oxide, see Ge-00064 Bis[tris[(trimethylsilyl)methyl]stannyl]mercury, Sn-00399 Bromo( 7 -2,4-cyclopentadien-1 -yl)lead, Pb-00035 Bromo( 7 -2,4-cyclopentadien-1 -yl)tin, Sn-00086 Bromodimethylstannane, Sn-00022... 

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