2- Methyl-5- thiophenes rearrangements

Thiophene, 2-methyl-5-(mesitylsulfonyl)-Truce-Smiles rearrangement, 4, 825 Thiophene, 2-methyl-3-nitro-acidity, 4, 799... 

The pronounced acidity of the bridgehead hydrogen atoms in 4 (R = H) facilitates the regio-selective introduction of electrophiles. Rearrangements of 4 (R = H, Me, CHO, C02Me) catalyzed by dicarbonyldichlororhodium(I) lead to 4-substituted 1-benzothiepins 5,10 except in the case of R = Me where a mixture (1 1.3) of 3- and 4-methyl-l-benzothiepin is obtained (total yield 98 %). In the case of the dimethyl-substituted derivative 8 (R1 = R2 = Me), however, the rhodium(I)-catalyzed isomerization reaction leads to the thiophene isomer. 

Rearrangement of allyl 3-thienyl sulfide (45) gives 2-methyl-2,3-dihydrothieno[3,2- >]thiophene (46) [Eq. (21)]. 

Thienyl sulfides with the 2-position of the thiophene ring blocked, e.g., allyl 2-methyl-3-thienyl sulfide (51), also undergo sigmatropic rearrangement when heated in quinoline [Eq. (23)]. 2,6-Dimethyl-2,3-dihydro-thieno[3,4-Z ]thiophene (52) is formed, together with other products. 

Under these strong acid conditions, products from other rearrangements and acid cleavage reactions are sometimes found. For example, a mixture of 5-r-butyl-3-methyl-benzo[6]thiophene (the expected product), 6-f-butyl-3-methyIbenzo[6]thiophene and 3-methy benzo[6]thiophene was obtained on cyclization of p-t- butylphenylthioacetone with phosphorus pentoxide. During the cyclization of phenyl phenacyl sulfide to give a mixture of 2- and/or 3-phenylbenzo[Z ]thiophenes, small amounts of diphenyl disulfide and 5-pheny thio-3-phenylbenzo[6]thiophene were also formed (70AHC(11)177). 

Methyl- or 2-ethyl-benzo[Z> ]thiophenes are conveniently prepared by treatment of 2-benzo[6]thienyllithium with the appropriate alkyl sulfate <70AHC(11)177). Clemmensen or Wolff-Kishner reductions of the 2-acylbenzo[Z>]thiophenes are useful, but since acylation produces a mixture of the 2- and 3-acyl isomers (Section 3.14.2.4), these must be separated. Cyclization of phenyl phenacyl sulfide with hydrofluoric acid leads exclusively to 2-phenyl-benzo[6]thiophene, and 3-phenylbenzo[6]thiophene can be rearranged to the 2-isomer in hydrofluoric acid (Section 3.15.2.3.2). Aromatization of 2-cycIohexenylbenzo[6]thiophene, obtained by condensation of the 2-lithio reagent with cyclohexanone, gives 2-phenyl-benzo[6]thiophene, and the reaction is adaptable to the 2-(l-naphthyl) derivative also. 

Ring-closure techniques are more commonly used to obtain 3-alkylbenzo[6]thiophenes. Thus, acid-catalyzed cyclization of arylthio methyl ketones gives the 3-alkylbenzo[6]thio-phenes in good yield, with little rearrangement (equation 3). Formation of the 3-aryl-benzo[6]thiophenes by this approach is complicated, however, by rearrangement to the 2-isomer (Section 3.15.2.3.2). 3-Methylbenzo[f> Jthiophene is also obtained by decarboxylation of the corresponding 2-carboxylic acid (equation 4), readily available from ar-mer-captocinnamic acids (Section 3.15.2.1.1). 

The sequence with oxazole 73 also proves to be applicable to systems in which the double bond of the allylic alcohol fragment is incorporated into a heteroaromatic ring, such as in furfuryl alcohol (77a) and thiophene-2-methanol (77b).28 After hydrolysis of the oxazolone ring with water, V-benzoyl-3,3,3-trifluoro-2-(2-methyl-3-furyl)alanine (79a) and /V-benzoyl-3,3,3-trifluoro-2-(2-melhyl-3-thienyl)alanine (79b) are obtained. The 2-methylene helerocyclcs 78 originally formed in the Claisen rearrangement undergo rearomatizalion under the reaction conditions. 

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