Thiophene oxides Subject

The existence or nonexistence of conjugative effects involving the sulfone group in thiophene dioxides (a problem analogous to that in thiirene oxide and dioxide systems2,1 ) has been the subject of many studies resulting, nonetheless, in no unequivocal conclusion280. 

Thiophenes and Tetrahydrothiophenes. Thiophenes (thioles) are subject to aromatic hydroxylation tetrahydrothiophenes (thiolanes) undergo oxidation of the sulfur to give sulfoxides or sulfones. 

An enantioselective synthesis of (+)-estradiol has been accomplished from 1,3-dihy-drobenzo[c]thiophene 2,2-dioxide (306) by successive thermal S02-extrusion and cycloaddition (80HCA1703). Treatment of the optically active iodide (307) with two mole equivalents of the masked quinodimethane (306) in the presence of two mole equivalents of sodium hydride gave (308) as a 1 1 mixture of diastereoisomers. Thermolysis of this alkenic sulfone in 1,2,4-trichlorobenzene furnished the trans-anti-trans steroid (309) in 80% yield. Treatment of (309) with methyllithium gave the methyl ketone, which was subjected to a Baeyer-Villiger oxidation and then silyl ether-acetate cleavage to afford (-l-)-estradiol (310 Scheme 66). 

Selenides (290) and (292) were oxidized to the unstable selenoxides (298) and (299) by aqueous hydrogen peroxide under controlled conditions or by sodium metaperiodate. When selenoxide (298) was subjected to the Pummerer reaction using acetic anhydride in the presence of N- phenylmaleimide, a mixture of exo/endo adducts (144) was obtained in 58% yield, indicating the transient formation of the selenolo[3,4-c]thiophene (143 Scheme 100) <77H(6)1349). 

Sulfur oxidation of the thiophene ring leading to thiophene-1-oxides or thiophene-1,1-oxides is useful for modifying the chemistry of the thiophene ring and this subject has been reviewed <02CHC632>. The structure and physical properties of quinquethiophene-1,1-dioxides have been studied in detail <02T10151>. The mechanism for the oxidation of thiophene to a mixture of thiophene-l-oxide (trapped as a Diels-Alder adduct) and thiophen-2-one was studied using... 

Oxidation of the 5-hydroxybenzo[h]thiophenes 55 with IBX gave the rmstable intermediate o-quinones 56, which were not isolated, but subjected directly to Diels-Alder reactions with the dienes 57, producing the tricyclic systems 58 <05T9097>. 

Heterocyclic compounds such as furan, thiophene, and pyrrole are subject to oxidation. Similar to secondary allyUc alcohols, 2-(l-hydroxyalkyl) derivatives of these heterocychc compounds are also good substrates for kinetic resolution using a titanium-tartrate and TBHP system (Scheme 15). 

The stereochemistry of alkylation of the carbanion generated from 2-methylbenzo[6]thiophen-3(2//)-one-l-oxide has been investigated <84CPB898>. The cis and trans isomers (265a) and (265b) were separately subjected to base treatment, followed by alkylation with RX (Scheme 50). The trans .cis ratio in the product mixture was determined by H NMR spectra. It was found that in both cases, the alkylation occurred stereoselectively cis to the S—O bond, the (266) trans cis ratio... 

Thiophene derivatives are subject to S-oxidation followed by conjugation with glutathione however, other routes of metabolism, involving ring cleavage, are also possible. The resulting mercapturic acid derivative is eliminated in the urine (Dansette et al., 1992 Valadon et al., 1996). 

A variety of 2- or 3-substituted thiophenes, as well as benzothiophenes, have been subjected to the catalytic direct arylation [3, 9, 10]. As expected, 2,2 -bithio-phene can be diarylated at the 5,5 -positions (Equation 10.47) [72], although the use of a bulky phosphine is of key importance for this reaction. 2,2 -Bithiophene protected by benzophenone at the 5-position reacts with aryl bromides, initially with liberation of the ketone (see Scheme 10.6, to give 5-aryl-2,2 -bithiophene, which is then arylated at the 5 -position (Equation 10.48) [72]. 5-Bromo-2,2 -bithio-phenes undergo oxidative homocoupling in the presence of a palladium complex and a silver salt (Equation 10.49) [73]. 

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