Lewis Acid Catalysis in the Oxidative Cycloaddition of Thiophenes¹

Abstract

Thiophenes 1 were treated with m-chloroperbenzoic acid (m-CPBA) under BF(3).Et(2)O catalysis to afford thiophene S-monoxides. These could be reacted in situ as intermediary species with a number of dienophiles to provide arenes (with alkynes as dienophiles) or 7-thiabicyclo[2.2.1]hept-2-ene 7-oxides (with alkenes as dienophiles). It was also possible to isolate thiophene S-monoxides in solution and to cycloadd them in a second step. In either way it could be shown that the use of BF(3).Et(2)O enhances the yields of the oxidative cycloaddition of thiophenes considerably. Moreover a greater variety of dienophiles (29a, 29b, 29c) could be reacted with thiophenes than in the case of the noncatalyzed reaction. All cycloadditions catalyzed by BF(3).Et(2)O give only a single diastereoisomer as cycloadduct. The reactions show a high pi-facial selectivity, a fact that can be explained by the Cieplak-effect. Without added dienophiles, 2-methylthiophene (1e) gave a single dimer (36) of 2-methylthiophene S-monoxide, whereas 2,5-dimethylthiophene (1a) gave three dimers (32a-c). In the case of tetrasubstituted thiophenes, thiophene S-monoxides (e.g., 31b and 31c) could be isolated in substance.

Analogy between sulfuryl and phosphino groups: the aromaticity of thiophene-oxide

“…By steric shielding (in e.g., 2,5-diadamantyl- [26], 2,5-di-tert-butyl [26], and also in 2,3,4,5-tetramethylthiophene-oxide [27]) or by the incorporation of the double bonds into the highly stable aromatic system of anellated benzene rings (in dibenzothiopheneoxides [28]) the reactivity is reduced, making these thiophene-oxides synthesizable.…”

The chemistry of thiophene S-oxides1 and related compounds

“…Interestingly, sesquioxides can also be found in oxidatively treated, thiophene-containing fuel. 6 That the oxidation of thiophenes can be stopped at the monoxide stage is a matter of adding a Lewis acid such as boron trifluoride etherate in the case of the peracid oxidants 5,7 and of a proton acid such as trifluoroacetic acid in the case of hydrogen peroxide (Scheme 1). 8 The same holds true for the oxidation of benzothiophenes 10 to benzothiophene S-oxides 4, 9,10 the acid most likely having a dual function, namely to activate the peroxide/peracid and to complex to the monoxide once it is formed, hindering by the withdrawal of electron density from sulfur a further oxidation to the corresponding thiophene-or benzothiophene-S,S-dioxide.…”

Detection of the damage caused to DNA by a thiophene-S-oxide using an electrochemical DNA-biosensor

“…Thiophene-S -oxides were prepared directly from the corresponding thiophenes by oxidation with m -CPBA in the presence of BF 3 ×/Et 2 O as a Lewis acid [23]. Typically, the reaction is carried out at low temperature, where the Lewis acid both activates the peracid as well as stabilizes the thiophene-S -oxide formed through complexation, thus hindering further oxidation of the product to the more stable thiophene S ,S -dioxide species.…”