Synthesis of 3-substituted furans by directed lithiation and palladium catalysed coupling

Article abstract of DOI:10.1016/S0040-4020(01)82041-X

The 5-position of the furan ring of 4,4-dimethyl-2-(2-furyl)oxazoline (1a) was protected by a trimethylsityl group. The product, compound (2a), was then lithiated at the 3-position with sec-butyllithium and converted to the bromozinc species (2d) with zinc bromide. Coupling reactions with a range cf aryl-, acyl-, and vinyl halides were performed with Pd(PPh3)₄ as catalyst. The reaction with (1-bromoethenyl)- trimethylsilane is abnormal in that it gives a mixture of two products (21) and (2m). The origin of the abnormal product (21) is discussed. The coupling reactions of this silane with 2-thienyl-, 2-furyl-, and phenyl-zinc bromide have also been carried out: in each case, a mixture of the expected coupling product and an isomer, the ethen-2-yltrimethylsilane, was obtained. The ratio of products is shown to depend upon the temperature at which the coupling is carried out. 4,4-Dimethyl-2-(2-thienyl)oxazoline (1b) was lithiated at the 3-position of the thiophene ring and coupled to iodobenzene without protection of the 5-position.