Thiophene Ylide Rearrangement

Thermolysis of the ylide 1 in anisole containing a catalytic amount of BF3.0Et2 gives a mixture of products, the major component of which (35%) is 2. 

Reaction of 1,2-dimethylcyclohexene with the ethylene glycol acetal of acrolein in methylene chloride in the presence of 25 mol % of BF3.0Et2 at -78 to -10°C for 2 hours gives a 70% yield of the cycloadduct 1 in a formal 2k + 2% intermolecular cycloaddition. All of the evidence for this and related reactions, however, indicates a stepwise mechanism for the formation of 1. 

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The oxathiocins remain extremely rare members of the class of 1,4-diheterocins. Ring-formation reactions, through either unimolecular cyclization or condensation, have been scarcely examined, and those cases reported suffer from low yields. The thiophene ylide rearrangement route provides ready access to the fully unsaturated oxathiocin ring system, but demands the use of 2,5-dihalo-thiophenes. This may not represent an insurmountable problem, and in fact the halides may permit functionalization of the oxathiocins through, for example, nucleophilic displacement, but apparently no such studies have yet been carried out. 

Shimizu and co-workers reported that thermal decomposition of A4-thiabenzenes ylides afforded both thienofuran and thiophene derivatives in addition to the expected alkyl-rearranged products. A plausible mechanism was proposed with a [3.1.0] bicyclic sulfonium salt 9 as the key reactive intermediate <2001J(P1)2269>. Warren and co-workers, in their study of stereospecific phenysulfanyl migrations, found that [l,4]-sulfanyl participation could compete with the usual [l,2]-sulfanyl participation <1999SL1211>. Rearrangement of alcohol 18 with TsCl in pyridine gave an inseparable mixture of isomeric chlorides, 19 and 20, in a ratio of 52 48, as shown in Equation (3). 

The view has been expressed that a primarily formed ylide may be responsible for both the insertion and the cyclopropanation products 230 246,249). In fact, ylide 263 rearranges intramolecularly to the 2-thienylmalonate at the temperature applied for the Cul P(OEt)3 catalyzed reaction between thiophene and the diazomalonic ester 250) this readily accounts for the different outcome of the latter reaction and the Rh2(OAc)4-catalyzed reaction at room temperature. Alternatively, it was found that 2,5-dichlorothiophenium bis(methoxycarbonyl)methanide, in the presence of copper or rhodium catalysts, undergoes typical carben(oid) reactions intermole-cularly 251,252) whether this has any bearing on the formation of 262 or 265, is not known, however. 

Thermolysis of the ylide (15) in thiophene results in ready rearrangement to dimethyl thiophene-2-malonate (16). The same product is obtained if the thermolysis is carried out in the presence of 2-methylthiophene or cyclohexene, proving that the rearrangement occurs by an intramolecular process (78CC85). However, when 2,5-disubstituted thiophenium ylides are thermolyzed, dissociation to carbenoid species seems to occur. This reaction is further discussed in Section 3.14.2.9. 

Cyclopropanated products from thiophene can undergo further transformations. For instance, irradiation of tetraphenyldiazocyclopentadiene in the presence of 2,5-dimethyl-thiophene gives the product (248) by rearrangement of the cyclopropane (247) (72CC1257). With thiophene as the substrate the ylide (249) was also obtained. Likewise, ylide (15) is formed by photolysis of diazomalonic ester in the presence of thiophene (77JOC3365). 

Carbenoid insertion into the C-S bond of 2-substituted thiophenes competes with cyclopropanation at the C=C bonds. Formation of the ylide 402 and hence a thiopyran by way of a Stevens rearrangement is the dominant pathway for 2-(methylthio)thiophene, but is less significant for the 2-methyl and 2-trimethylsilyl derivatives (Scheme 115) <1998T15499>. 

The interaction between thiophenes and oxocarbenoids, in general, leads to sulfur ylides 42 as the initial products. Depending on the substituents R R, R and the temperature, these ylides can be isolated (R, R carbanion-stabilizing substituents), rearrange to a 1,4-oxathiocin (2,5-dichlorothiophene and ethyl 2-diazo-3-oxobutanoate ° ) or to 6-acyl-2-thiabicyclo[3.1.0]hex-3-enes, 2-acyl-2//-thiopyrans or 2-acylmethylthiophenes. Theoretical calculations and experimental results suggest intermediate 43 as the common precursor for the latter three products. 

Even thiophene itself will react with carbenes, at sulfur, to produce isolable thiophenium ylides, and in these, the sulfur is definitely tetrahedral. The rearrangement of thiophenium bis(ethoxycarbonyl) methylide to the 2-substituted thiophene provides a rationalisation for the reaction of thiophene with ethyl diazoacetate, which produces what appears to be the product of carbene addition to the 2,3-double bond perhaps this proceeds via initial attack at sulfur followed by S C-2 rearrangement, then collapse to the cyclopropane. Acid catalyses conversion of the cyclopropanated compound into a thiophene-3-acetic ester. ° 2,5-Dichlorothiophenium bis(methoxycarbonyl)methylide has been used as an efficient source of the carbene simply heating it in an alkene results in the transfer of (Me02C)2C to the alkene. ... 

For the sake of convenience, the rearrangements of thiophene S,C-ylides and S,N-ylides are discussed in Section 2.10.3.3. 

It was mentioned earlier that the S,C-ylide (139b) generates a carbenoid species and dichloro-thiophene in the presence of transition metal catalysts. Thermolysis of (139b) in the absence of such metal catalysts leads to (145) through an intramolecular rearrangement <84CHEC-i(4)74i, 89AHC(45)151>. 

Sigmatropic rearrangement of the sulfonium ylides from 3-(bromomethyl)thiophene and 2-(bromomethyl)benzo[f)]thiophene has been reported <8980958). Treatment of the bromomethyl compounds with dimethylsulfide gave the sulfonium salts. These were deprotonated (NaOEt or NaH) to generate the ylides. Sommelet-Hauser rearrangement of the ylides gave the products (458) and (459) (Scheme 93). 

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