Carboxylic acids sulfenylation

Similar sulfenylation reactions of the 2-subsdtuted cyclic enamines of -keto carboxylic acid anilides are also possible, The trifluoromethanesulfenyl substitution takes place according to ring size Sulfenylation occurs at positions 2 and 5 with five-membered rings, at posibon 6 with six-membered tings, and at position 7 with seven-membered rings [5J (equation 4) (Table 1). Acid hydrolysis of the enamines proceeds readily to form the corresponding keto compounds. 

A concerted elimination-cyclization mechansim, involving a sulfenyl halide in a 1,3-butadiene-1-thio system, is the most probable mechanism for the formation of benzo[6 Jthiophenes from cinnamic acids or 4-aryl-2-butanones by treatment with thionyl chloride. The reactions shown in Scheme 5 have been carefully worked out, and the intermediates isolated (75JOC3037). The unique aspect of this synthesis is the reduction of the sulfinyl chloride (a) by thionyl chloride to form the sulfenyl chloride (b). The intermediate (b) was isolated and converted in pyridine to the 3-chlorobenzo[6]thiophene-2-carbonyl chloride in 36% yield (73TL125). The reaction is probably initiated by a sulfenyl ion attack on the aromatic ring, since it is promoted by electron-releasing groups para to the site of ring closure. For example, when X in (36) was N02, a 23% yield of (37), a mixture of 5-and 7-nitro derivatives, was obtained, but when X in (36) was OMe, a 54% yield of (37) was obtained, contaminated with some 3,4-dichloro-5-methoxybenzo[6]thiophene-2-carboxylic acid. 

The sulfmylation of esters, - lactones, carboxylic acids, > amides and lactams may be effected by reacticm of the corresptHiding lithium enolates in THF at -78 to 0 C with dimethyl or difdie-nyl disulfides, or, less conunmily, with methyl or fdienyl sulfmyl halides. The enolates of ketones, however, are insufficioitly nucleq diilic to react with dialkyl sulfides unless HMPA is added to the re-acticm mixture, although they do react smoothly with diaryl sulfides. This difference allows the selective sulfenylation of esters in the presence of ketones (entry 5, Table 3). ... 

These various intermolecular a-acetoxylation reactions have intramolecular counterparts. For example, treatment of the sulfinylbutanoic acid shown in equation (11) with acetic anhydride containing p-toluenesulfonic acid yields a sulfenylated butanolide, the carboxylic acid function having intercepted the a-thiocarbocation intermediate. Yet another demonstration of Ae intramolecular process, due to Al-lenmark, is the cyclization of o-carboxyphenyl benzyl sulfoxide with acetic anhydride to form the 1,3-benzoxathian-4-one shown in equation (12). This reaction was also conducted with one of the... 

When suitably constructed unsaturated compounds, such as olefinic alcohols or unsaturated carboxylic acids 1, react with phenylsulfenyl chloride the formation of the corresponding bicyclic /j-phenylthio derivatives 3 takes place31. This presumably proceeds via the intermediacy of an episulfonium ion 2 which is captured intramolecularly by the hydroxy group leading to the final sulfenylation product 3 in high yield. 

Electrolysis of a-sulfenyl carboxylic acids in protic solvents gives ketones, presumably via replacement of the carboxyl group with alkoxyl or acetoxyl groups and a subsequent two-electron oxidation of the sulfenyl moiety [Eq. (32)]. (This discussion is postponed to Sec. IV.D.)... 

Photolytic cleavage reactions (e.g., of c-nitrobenzyl, phenacyl, and nitrophenyl-sulfenyl derivatives) take place in high yield on irradiation of the protected compound for a few hours at 254-350 nm. For example, the c-nitrobenzyl group, used to protect alcohols, amines, and carboxylic acids,has been removed by irradiation. Protective groups that have been removed by photolysis are described at the appropriate places in this book in addition, the reader may wish to consult five review articles." - ... 

Oxidative decarboxylation. Trost and Tamura have described a two-step procedure for conversion of a carboxylic acid to a ketone with loss of one carbon atom. The acid is converted into the dianion with lithium diisopropyl-amide (THF or THF-HMPT) followed by sulfenylation with dimethyl disulfide. In the second step, solid NCS is added to a mixture of the sulfenylated acid (1) and sodium bicarbonate in an alcohol (usually ethanol) CO2 is evolved immediately. Aqueous work-up after 1-3 hr. gives the ketal (2), which is hydrolyzed to the ketone (3). 

Nucleophilic substitution, e.g. the preparation of thiocyanates from lipophilic alcohols, can be facilitated by substrate hydrophilation via ammonioethanesulfonic acid esters (betylates)i . Mercaptans can be easily prepared from alcohols with inversion of configuration via thiolic esters prepared with thioacetic acid in the presence of 2-fluoro-pyridinium salts . C-Sulfenylation of / -dicarbonyl compounds with mercaptans by air oxidation in the presence of tetraethylammonium fluoride has been reported . Activated thiolic and selenolic esters can be prepared at room temperature from carboxylic acids and aryl thiocyanates or selenocyanates in the presence of tri-n-butylphosphine i. Phenylselenolactones have been obtained under very mild conditions from unsaturated acids and benzeneselenyl chloride. ... 

A subsequent study by Jprgensen et al. also demonstrated the enantioselective a-sulfenylation of (S-dicarbonyl compounds 420 using l-alkylsulfanyl[l,2,4]triazole derivatives 419 in the presence of a catalytic amount of cinchona alkaloid derivative 421. The use of cyclic (S-dicarbonyl compounds ensured the introduction of a quaternary sulfur center however, the observed enantioselectivity was modest in 51-89%. In 2009, Zhu and co-workers reported that a chiral a,a-diaryl prolinol 424 efficiently catalyzed the enantioselective sulfenylation of (S-ketoesters 420 using N-(phenylthio)phthalimide 423 as a sulfur electrophile. The absence of racemizable C—H bonds led to the optically enriched a-sulfenylated products 425 in excellent enantio-selectivities. In 2010, Fu developed a method for catalytic asymmetric 7-sulfenylation of carbonyl compounds using 2,3-allenoates 426 in the presence of a chiral bisphos-phine, TangPhos 427, and a bulky carboxylic acid 428. ... 

For the formation of acid chlorides, the competing reactions of concern are a-oxidation and acid-catalyzed degradation. The use of solid Sodium Carbonate in the reaction mixture can minimize the latter for some compounds. As shown in eq 7, even simple carboxylic acids with enolizable hydrogens a to the carboxylic functionality are subject to oxidation under standard chlorinating conditions. Since the unoxidized acid chloride is the precursor to the sulfenyl chloride, careful attention to stoichiometry and reaction time can effectively minimize this problem. 

Sulfenyl..., Thia. .. Thioacetais s. Mercaptals Thioacylamines (s. a. Carboxylic acid thioamides)... 

The sulfenyl carboxylate is, on complete exclusion of moisture, a stable, colorless liquid, which on irradiation with UV light decomposes to FC(0)SCFs and CO2. The sulfane is a good starting material for the synthesis of additional perfluoro compounds By means of fluorine-chlorine substitution with BCI3 (20°C, 2 days), it is possible to obtain C1C(0)SCF3, whose existence previously could be shown only by mass spectrometric study of the products of irradiation of a mixture of CFsSCl and CO (237). As an acid chloride, ClC(0)SCFs can be esterified with alcohols, but hydrolysis to the free acid fails. 

Buffer catalysis of the hydrolysis of phenyl (311 R = Ph) and methyl (311 R = Me) benzenesulfinates to give the sulfinic acid (312) and alcohol ROH is strongly accelerated by both carboxylate and amine components of the buffer which give Bronsted /i values of approximately unity on separate lines. The carboxylates are about 44 tunes more effective than amines of similar basicity. A concerted. S n2 mechanism with a hypervalent intermediate (313) is proposed for the nucleophilic reaction of these esters.286 The reaction of the thiosulfinate esters (314) with sulfenyl chlorides RSCI and sulfenate esters (315) to give sulfinyl chlorides and disulfides and sulfinate esters and disulfides, respectively, has been studied.287 Hydrolysis of 2-(3-aminophenyl)sulfonyl-ethanol hydrogensulfate gives under different conditions various products such as the ether (316) and the sulfone (317).288... 

Electrc hilic reagents capable of Mnging about Pummerer rearrangement include inoiganic and organic acids, carboxylic anhydrides, acyl halides, isocyanates, caibodiimides, irimethylsilyl halides and triflate, sulfonyl and sulfenyl halides, phosphorus pentoxide and many typical Lewis acids such as boron... 

MO calculations have been carried out on the isomerization of cyclopropane to propene, and the MNDO method has been used to study the reaction pathway and to optimize the structure of reactant, transition structure, and product of the ring opening reaction of bicyclo[1.1.0]butane. Various methods have been employed to estimate the rate constants for ring opening of the 2-cyclopropyl-2-propyl radical. 1-Acceptor-1-sulfenyl-substituted 2-vinylcyclopropanes of the type (430) have been found to afford 6-sulfenyl-a,jS y, -unsaturated carboxylic esters and nitriles (431) upon treatment with acid, by a process which involves C(l)—C(2) bond fission and a novel 1,5-sulfenyl rearrangement (see Scheme 110). It has been shown that the benzophenone-sensitized photolysis of vinyl norcaradiene derivatives, such as 5-(2-methylprop-l-enyl)-3-oxatricyclo[4.4.0.0 ]deca-7,9-dien-4-ones (432), results in the regioselective cleavage of only one of the cyclopropyl c-bonds to afford isochroman-3-one derivatives (433). It has been reported that the major product obtained from the reaction of structurally diverse a-diazo ketones with an electron-rich alkene in the... 

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