2-thiophenyl derivative

The allylic C-H functionalization has been effectively used for the syntheses of pharmaceutical targets. The reaction of the 3,4-dichlorophenyl derivative 11 with 1,4-cyclohexadiene generated the C-H insertion product 12 with 93% ee, which was then readily converted to (+)-indatraline using conventional chemistry (Equation (29)).88 The thiophenyl derivative 13 was also capable of a C-H insertion to form 14 with 88% ee. A few trivial steps converted 14 to the cholinergic agent (+)-cetiedil (Equation (30)).89... 

Another route to thioglycosides from hemiacetals involving a cyclization of an open-chain sulfide has been described recently. A Wittig-Horner reaction afforded the Q ,/3-unsatu-rated thiophenyl derivative, which then was treated with iodonium reagents to induce cyclization to afford 2-iodo-l-thioglycosides, which are good precursors for 2-deoxy-sugars (O Scheme 13) [167]. 

The nature of the alkene substitutent can play a key role in the success of the AA methodology. Although the furyl and thiophenyl derivatives of the ester 34 gave good regio- and enantioselectivities, the pyrrol analogues did not undergo reaction (Scheme 3.43) [367, 368],... 

Other methods for the selective preparation of thiophenyl derivatives have eiIso been described [20]. 2-Alkyl-3-sulfolenes were converted to 3-thiophenyl derivatives (135) by treatment with phenylsulphenyl chloride in the presence of Et3N, and 3-thiophenylsulfolenes were alkylated selectively via their lithium anions, providing (136a-d) (Scheme 6.40). 

With a-hydroxy ketones and their related tosyloxy derivatives. The imidazo [2,T ]thiazole 364 was prepared by acetic acid-catalyzed cyclocondensation of 2-hydroxy-l,2-diphenyl-ethanone with thiophenyl-substituted 2-aminothiazole 363 (Equation 163) <2002MI110>. Under MW irradiation and in the presence of montmorillonite K-10 clay, a mixture of a-tosyloxyketones 365 and 2-imidazolidinethione led to the substituted 5,6-dihydro-imidazo[2,l- ]thiazoles 366 (Equation 164) <1998J(P1)4093>. When using a-tosyloxyacetophenone, prepared by reaction of acetophenone with [hydroxyl(tosyloxy)iodo]benzene (HTIB), 5-aminopyrazole 367 could be converted to imidazo[l,2- ]pyrazole 368 in basic medium (Equation 165) <2005JHC209>. 

Takahashi and coworkers described an effective sialylation method utilizing the N-Fmoc, N-Troc and N-trichloroacetyl-P-thiophenyl sialosides (Scheme 4.6d) [167]. It was found that the N-Troc derivative of N-acetylneuraminic acid performed better than the corresponding N-Fmoc derivative. An N-Troc P-thiosialoside was applied for the synthesis of glycosyl amino acids by one-pot glycosylation [167]. Importantly, it was found that the N-Troc protecting group could be converted into an acetamido moiety without causing racemization of the peptide. 

Thiophenyl acetates (366 R = Me) and propionates (366 R = Et) react with electrogenerated polysulflde ions S3 in DMF to yield thiocarboxylate ions, thiolate ions, and phenyl tetrasulfanide (367), the last deriving from the reaction of thiolate ions with sulfur (Scheme 48). Smdies of the aminolysis by a set of substimted anilines of Y-aryl dithio-2-thiophenates (368 X = S) and dithio-2-furoates (368 X = O) in acetonitrile have shown that the rate-determining step in these reactions is the departure of the thiophenolate ion from the zwitterionic tetrahedral intermediate T= = (Scheme 49). Experiments with deuteriated anilines yielded k i/IcQ values of 1.7-1.9,... 

Japanese workers have also displaced a methyl sulfone group with a variety of nucleophiles. Thus they were able to introduce, ethoxy, thiophenyl, aniline, and malonic acid groups in to the pyridine A -oxide derivative (105). Acid hydrolysis produced the 2-one compound, while reduction with sodium borohydride cleaved off the methylsulfone group <87CPB1030>. 

In line with previous experiments, a series of heteroaryl-substituted dimethylamino-functionalised titanocene dichlorides have been synthesised and evaluated [23], as shown in Fig. 7. Unfortunately, no uniform pattern compared with benzyl-substituted titanocenes was detected. A decrease in cytotoxicity was observed for the thiophenyl-substituted titanocene (18) from 150 pM (for the unbridged analogous compound 6) to 240 pM. On the other side, a significant increase in cytotoxicity was observed for the furyl-substituted titanocene (19) (160-28 pM) and especially for the /V-methyl pyrrole derivative (20), which exhibits an IC50 value of 5.5 pM. In fact, titanocene 20 is one of the most cytotoxic substituted titanocene dichlorides that have been reported up to now. This represents an impressive 400-fold increase in cytotoxic activity compared with the unsubstituted Cp2TiCl2, which reached Phase II clinical trials. 

C-Glycosides. Thiophenyl glycosides undergo ready free-radical allylation with allyl- or methallyltri- -butyltin. Thus the L-lyxose derivative 1 reacts with allyltri-/ -butyltin under photochemical initiation to give 2 and 3 in the ratio 90 10. The reaction... 

Phenolic esters are obtained similarly. The presence of a nitro group in the aromatic nucleus and the use of pyridine as solvent facilitates the reaction. This reaction is recommended for the characterization of phenols. 2,4,5-Trichlorophenyl-, pentachlorophenyl-, 4-nitrophenyl- and thiophenyl esters of N-acylamino acids are prepared in this manner. These aromatic esters are used in the stepwise lengthening of peptides, du Vigneaud and coworkers synthesized lysine vasopressin from a nonapeptide which they prepared stepwise using the nitrophenyl ester method. Room temperature esterification of dicarboxylic acids and diphenols are also carbodiimide mediated using the 1 1 complex derived from DMAP and p-toluenesulfonic acid as catalyst Methacrylic acid is also esterified with phenols using carbodiimides and DMPA to mediate the reaction. ... 

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