Phenylthio compounds

The photolysis of 4-substituted 2,3-dimethyl-3-isoxazolin-5-ones has been studied. Irradiation in methanol or ethanol with a 100 W high-pressure mercury lamp through a Pyrex filter of a 4-phenylthio compound produced a semithioacetal (Scheme 5). In contrast, an H, Cl or OPh moiety gave no reaction. The use of alkylthio substitution gave similar products. Cyclic compounds yielded cyclic products (Scheme 5), and the photolysis of (29) in benzene... 

R1 = R2 = H, has been used in alkylations to give a,/J-unsaturated aldehydes in good yield85. Reaction occurs entirely a to PhS and y to MeO leaving an easily hydrolysed vinyl ether as the product. The substituted reagents 144 must be carefully purified as PhSH easily displaces MeOH to give the less useful bis-(phenylthio) compounds. 

An attempted enantioselective synthesis of ipalbidine from the protected (S)-prolinol 860 was based on the regioselective 6-exo-trig cyclization of the radical intermediate derived from the reaction of the phenylthio compound 861 with tributyltin hydride (Scheme 111) (577). The reaction gave a 1 1 mixture of two indolizidin-5-one diastereomers 862 in 65% yield. At the end of the synthesis, the target 842 was found to possess virtually no optical activity. The most likely candidate for racemization is the aldehyde 863, which might scramble under the basic conditions required for the subsequent Wittig reaction. 

A mixture of 2-t-butylfuran and 2,5-di-t-butylfuran is obtained by the action of t-butyl chloride on furan in the presence of mesitylene nolybdenum tricarbonyl." The intermediate in the nitration of furan-2-aldehyde in acetic anhydride has been identified as compound (26). Treatment of 5-bromo-2-furoic acid with sulphur tetrafluoride in hydrogen fluoride yields the dihydrofuran (27). Bromo-furans are converted into aryl-furans by crosscoupling with aryl Grignard reagents in the presence of nickel(II)-phosphine complexes. 2-Furoic acid is lithiated at position 5, 3-furoic acid at C-2. 2-Methylfuran yields the 5-methylthio-derivative by lithiation and subsequent treatment with dimethyl disulphide. The corresponding phenylthio-compound (28) has been converted into a series of 4-substituted 2-methyl-furans (29 R = alkyl, MeaSi, CO2H, or RCHOH) by the sequence bromi-nation, lithiation, treatment with the appropriate electrophile, and, finally, desulphurization with Raney nickel. 2-Lithiofuran reacts with copper(II)... 

In the field of reactions of thioglycosides the photobromination of phenylthio compounds has been covered in a review. As has been noted before, and has been used usefully in synthesis of 2-deoxy compounds, the alkylthio group of thioglycosides may migrate to C-2 under certain conditions. Thus, as well as compound 93 giving the expected 2,3-orthoester on treatment with alkyl orthoesters in acid conditions, it gave compound 94... 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

Scheme 8 summarizes the construction of the requisite building blocks 40, 41, and 50. Alkylation of the lithio derivative of l-(tri-methylsilyl)-3-phenylthio-l-propyne (42) with 3-iodo-l-(tert-butyl-dimethylsilyloxy)propane in the presence of HMPA affords compound 43 in 90% yield. Selective desilylation of the protected alcohol is achieved by warming 43 to 40 °C in ACOH-THF-H2O... 

Among the a-hetero-substituted chiral organometallic reagents, a-lithio ethers 2 are an important class of compounds. A general route to these compounds is the reductive lithiation of a-(phcnylthio) ethers 1 with lithium (dimethylamino)naphthalenide (I.DMAN)4,5. The generality of this method lies in the ready availability of various types of a-(phenylthio) ethers. 

Introduction of the phenylthio group onto the 5-carbon atom of alcohols can have valuable synthetic applications. 5-Phenylthio alcohols can be oxidized to the corresponding 5-sulfoxides and sulfones (with their versatile reactivities) or they can be deprotonated by strong base converting the 5-carbon atom to a nucleophilic species. Conversion of 5-phenylthio alcohols to the corresponding 5-carbonyl compounds can be achieved via halogenation followed by subsequent hydrolysis. In this way an inversion of the reactivity of the 5-carbon atom may be accomplished and it can react as an electron acceptor. 

The iodomethyltin compounds react with amines to give aminometh-yltin compounds, RsSnCHjNRj, and with phosphines to give the phos-phonium ions, MeaSnCHjP Rs, and tris(tributylstannylmethyl)amine has been prepared from (tributyltin)lithium and tris(phenylthio-methyDamine (285). 

Phenylthio acetals are much more easily prepared from the corresponding 4-acetoxy-l,3-dioxanes [45] (Eq. 29). The dioxane 125 gave the phenyl sulfides 185 in essentially quantitative yield on treatment with BF3 OEt2 and thiophenol at -78 °C. This method has been used to prepare compound 185 on a 40 g scale. 

Nicolaou and coworkers reported a new method for preparing glyco-syl fluorides (38) from phenyl thioglycosides (37) by treatment with di-ethylaminosulfur trifluoride (DAST)-A -bromosuccinimide (NBS), or HF-pyridine-NBS, the phenylthio group of the thioglycosides being initially activated by NBS. Thus prepared were compounds 39, 40, and 42 (see Table I) and 3,4-C)-carbonyl-2,6-dideoxy-3-C-methyl-L-n Z)ohexo-pyranosyl, 2-azido-2,6-dideoxy-3,4-0-isopropylidene-D-altropyranosyl,... 

The identification of the HIV-1-specific non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a separate class of HIV inhibitors was heralded by the discovery of the tetrahydroimidazo[4,5,1 -// .][ 1,4]benzo-diazepin-2(l //)-onc and -thione (TIBO) derivatives (Fig. 7) [58,59] and 1 -(2-hydroxyethoxymethyl)-6-(phenylthio)thymine (HEPT) derivatives (Fig. 8) [60,61]. The first TIBO derivatives (R82150, R82913) were the first NNRTIs [58] postulated to act as inhibitors of HIV-1 RT [59], For the HEPT derivatives it became evident that they also interact specifically with HIV-1 RT after a number of derivatives (i.e., E-EPU, E-EBU, and E-EBU-dM) had been synthesized that were more active than HEPT itself [62,63]. Following HEPT and TIBO, several other compounds, i.e., nevirapine, pyridinone, and bis(heteroaryl)piperazine (BHAP), were... 

Cyclopentadiene (6) added to 4 at room temperature. The reaction was complete within 5 h and gave a mixture of endo/exo-86a in 90% yield. The 2-phenylthio derivative 85 (X = SPh) showed similar reactivity, while the unsubstituted compound 52 reacted more slowly (Table 8) [15,17]. 

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