Thiophene 5-ylids, formation

When A.A-dimethylisoindolinium bromide is treated with phenyl-lithium, it gives V-methylisoindole via the ylid (54).2 59,60 An attempt to prepare benzo[c]thiophene via the analogous ylid (55) failed. Thus, when l,3-dihydrobenzo[c]thiophene methylsulfonium iodide was treated with phenyllithium, it gave a mixture of methyl phenyl sulfide, spiro[5.5]-l-methylthio-2,3-benzo-6-methylthio-methyleneundeca-7,9-diene (56), and 3,4-bis(methylthio)-l,2 5,6-dibenzo-l,5-cyclooctadiene (57).59,60 The formation of methyl phenyl sulfide may be explained by the formation and ring cleavage of compound 58, and compounds 56 and 57 arise by Diels-Alder dimerization of the o-quinodimethane (59) formed by ring cleavage of the ylid (55). 

The first reference to the formation of thiophenium ylids by carbene addition to thiophene appeared in 1972, when Durr and co-workers noted that pyrolysis of diazotetraphenylcyclopentadiene in thiophene resulted in a low yield of the ylid 14, although no information on the yield of the reaction or the physical or spectroscopic properties of 14 were given (72TL1257). 

These two reports clearly demonstrate that thiophene can form ylids, despite the considerably reduced nucleophilicity of the sulfur atom and that stable thiophenium ylids might be found. This was subsequently confirmed with the observation that the photolysis of dimethyl diazomalonate in thiophene result in the formation of 15, which was isolated in low yield as a stable crystalline solid (77JOC3365). It was subsequently demonstrated by my own group that thiophenium bis(alkoxycarbonyl)methylides could be formed in high yield using rhodium(II) acetate-catalyzed addition of diazomalonate... 

A detailed analysis of the reaction of diazoalkanes and a-diazocarbonyl compounds with thiophene has revealed that the formation of stable ylids is observed only with diazomalonic esters (79JCS(P 1)2624). Other a-diazocarbonyl compounds, such as diazoacetic esters, Meldrum s diazo, or ethyl diazoacetoacetate, do not generally give rise to stable ylids. However, with tetrachlorothiophene under favorable conditions, the corresponding ylids may be isolated (84CC190). 

There can now be little doubt that the reaction of singlet carbenes and car-benoids with thiophene proceeds by attack of the carbene at the ring sulfur atom to generate the S,C-ylid. However, only in the special cases indicated above do these ylids enjoy any real stability. In the majority of cases, other products usually result from rearrangement of the intermediate ylids and the nature of the products formed is remarkably sensitive to both steric and electronic effects. Broadly speaking, six major reaction pathways have been observed (1) 2-substituted thiophene formation, (2) 2H-thiopyran formation, (3) formation of derivatives of 2-thiabicyclo[3.1.0]hex-3-ene, (4) 3-substituted thiophene formation, (5) oxathiocin formation, and (6) carbenic fragmentation. 

Formally, the insertion of a carbene(oid) into the 2,3-doubIe bond of the thiophene ring should result in the formation of the 2-thiabicyclo [3.1.0] hex-3-ene ring system. Copper(II)-catalyzed reaction of thiophene with diazomethane results in the formation of 24 (R = H) in modest yield (63TL1047). Analogously, the reaction of thiophene with ethyl diazoacetate yields 24 (R = COjEt) (22LA154). Although these reactions appear to be simple carbene insertion reactions, it is probable that this simple mechanism is not in operation. Rather, the cyclopropane derivatives 24 probably result from the initial formation of the ylid (e.g., 18), which subsequently rearranges. 

Oxathiocin formation occurs only in very special circumstances when the thiophene ring is substituted with chlorine at the 2- and 5-positions of the ring (88CC138). Reaction of ethyl diazoacetoacetate with 2,5-dichloro-thiophene under rhodium(II) acetate catalysis results in the formation of 2-methyl-3-ethoxycarbonyl-5,8-dichloro-l,4-oxathiocin (26, R = H, R = COjEt, R = CHj) (Scheme 3). In this reaction the intermediate ylid is not observed and the only isolated product is the oxathiocin. However, when diazodimedone (27) is used, the intermediate ylid has been isolated and... 

In light of the known reactivity of the thiophene S,N-ylids, a detailed examination of the reaction of thiophene with ethyl azidoformate has been undertaken. A careful product analysis revealed the presence of previously unreported products, such as 68, 70, and 75, which can be explained satisfactorily only in terms of the intermediacy of the thiophene S,N-ylid 66 (Scheme 12) (86TL1105). Thus, if the initial reaction of thiophene with the ethoxycarbonylnitrene generates 66, the products 68-70 may be rationalized in terms of a Diels-Alder dimerization to 67. Cheleotropic elimination of 69 from 67, followed by aromatization, would result in the formation of 68. Alternatively, 66 could undergo rearrangement by way of a bicyclic transition state (71) (cf. 33, Scheme 7) to a dipolar intermediate 72 (analogous to 35, Scheme 7). Proton transfer in 72 would then furnish 73 analogous to the 2-... 

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