Thioacetals, cyclization

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

Despite the latent reactivity of ketene thioacetals,3-4 some members of this class such as the title compound have been little studied, perhaps because of preparative inaccessibility. The only previously reported route to 2-methylene-1,3-dlthiolane involves monoacetylation of 1,2-ethanedithiol, cyclization to 2-methyl-1,3-dithiolan-2-yl perchlorate, and exposure of this salt to diisopropylethylamine in acetonitrile 5... 

A novel route to 2,3-dihydrothiophenes involved a titanocene-promoted carbene formation and subsequenct intramolecular cyclization onto a thiol ester <99SL1029>. Treatment of thioacetal 9 with the low-valent titanium complex 10 gave 2,3-dihydrothiophene 12 by intramolecular olefination of the thiol ester of titanium-carbene intermediate 11. Another metal-mediated cyclization onto the thiophene ring system involved the palladium-catalyzed cyclization of 1,6-diynes <99T485>. For example, treatment of thioether 1,6-diyne 13 with Pdlj in the presence of CO and Oj in methanol followed by treatment with base gave 14. 

An alternative route begins with 341 which is treated with ethyl thioacetate in the presence of K2CO3 and the resulting intermediate is cyclized to give 340f <1997H(45)1319> a monophenyl derivative (56%) is prepared in the same way <2005JHC661>. 

In the only report of the generation of a pyridazino[3,4- ][l,4]thiazine <1992JHC1409>, reduction of a 2-(3-nitropyridazin-4-yl)thioacetic acid derivative is accompanied by cyclization (Equation 164). 

Cyclization of benzophenones having an o -thioacetic acid, ester or amide group has been used in structure studies and to synthesize 3-phenylbenzo[6 ]thiophenes with specific substituents. Thus (57) was readily converted to (58 X = OH, OEt or NH2) as precursors to a variety of benzo[6 ]thiophenes (57AC(R)705>, and as precursor to the unequivocal synthesis of 3-phenylbenzo[6 jthiophene, to demonstrate a remarkable sulfur-catalyzed rearrangement (59AJC218). 

Cyclization of thioketals. The reagent (1) converts thioacetals and thioketals... 

The acid-induced cyclization of unsaturated thioacetals (19) gives anti-Markovnikov products (20), apparently involving sulfur elimination and readdition.37... 

Figure 5 Covalent coupling of cyclic peptide moieties to human serum albumin (HSA). The depicted cyclic peptide, C SRNLIDC, in which C denotes the cyclizing cysteine residues, mimics the receptor binding site of PDGF-BB. First, a sulfhydryl group is introduced to the cyclic peptide by a reaction with succinimide-acetyl thioacetate (SATA). The primary amino groups of lysine in HSA are derivitized with maleimide-hexoyl-At-hydroxysuccinimide ester (MHS). Subsequently, the cyclic peptide is coupled to HSA. In this latter reaction, hydroxyl amine is used to remove the protecting acetate group from the sulfhydryl group of the cyclic peptide.

Nucleophilic displacement of iodide with thioacetate in the secosteroid 464 and subsequent simultaneous formate and thioacetate hydrolysis with concomitant cyclization provides the thiopyran ring four further steps are required to afford the 6-thiaallopregnanolone 465 (Scheme 159) <2006T4762>. 

Treatment of the 2-pyrrolyl allyl thioether (498) with acetic anhydride and quinoline at 170 °C (or in A jV-dimethylaniline at ca. 100 °C) results in a thio-Claisen rearrangement to give the 5-(3-allyl-2-pyrrolyl) thioacetate (499), whilst peracid oxidation of (498) produces the non-rearranged sulfone in low yield and Raney nickel reduction of (498) yields 3-propylpyrrole (78CJC221). The polyphosphoric acid-catalyzed cyclization of (2-pyrrolylthio) acetic acid (501 R = R = H) somewhat unexpectedly yields (502) via the Spiro intermediate, instead of forming the expected oxothiolane (500), which can be obtained by a Dieckmann cyclization of ethyl (3-ethoxycarbonyl-2-pyrrolylthio) acetate (501 R = Et, R = C02Et) (B-77MI30506). 

The acid-catalyzed cyclization of appropriate aryloxyketones formed benzo[l,2-6 5,4-6 ]difuran and benzo[ 1,2-6 4,5-6 ]difuran (63BSF1003). Another variation involved the cyclization of an aryl thioacetal to a benzo[l,2-6 4,5-6 ]dithiophene <86CB3198>. In investigations of the synthesis of a unit of the CC-1065 skeleton (see Section 7.21.12), a carbene derived from the azo-compound (59) constructed the cyclopropano-fused benzodipyrrole (60) by simultaneous formation of the heterocyclic ring and the cyclopropane ring <83TL4773>. 

Successive double deprotonation-alkylation of the dithioacetal 150 has also been performed in a one-pot procedure159-161 and used in cyclization processes for the preparation of indoles160 and the phenanthrene nucleus161. The dialkylation has been performed with primary alkyl iodides and bromides without additives. The cyclic sulfate 153 has been acy-lated by means of compound 151 and, after further deprotection of the thioacetal moiety, transformed into the corresponding 2-deoxy-D-arabinohexopyranose 154 (Scheme 43)162. 

Formation of 2-propyl-5-nitrobenzothiazole on reduction of 2,4-dinitro-butylth-iobenzene with sodium poly sulfite or trimethylphosphite has been observed [599], para-To] uenesul fonate 2,5-dimethyl-7-nitrobenzothiazole was obtained under the action of excess thioacetic acid on AK4-methyl-2,6-dinitrophenyl)pyridinium [600], The reaction involves the formation of 4-methyl-2,6-dinitrothiophenol acetate in which, under experimental conditions, one of the nitro groups is reduced to an amino group with subsequent cyclization, as shown in Scheme 2.109. 

The substrate for metathesis leading to product 103 was prepared in situ prior to cyclization in the form of a titanium-carbene complex, by desulfurization of thioacetals with low-valent titanium catalysts, such as Cp2Ti[P(OEt)3]2 (Scheme 42 <2000H(52)147 . 

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