Preparation of heteroaromatic compounds from the coupling of polyunsaturated alkyne derivatives and Fischer carbene complexes: Application in the synthesis of natural products and biologically important heterocycles.

摘要

New methodology was developed for construction of furanopyrone and thienopyrone ring systems utilizing the coupling of alkynylheteroaromatic carboxaldehydes with Fischer carbene complexes. These novel heterocycles, which were stable enough to isolate, underwent facile intramolecular Diels-Alder reactions with alkenes. The tandem furanopyrone formation-Diels-Alder reaction sequence was used as the cornerstone for a total synthesis of a cadinene natural product. This work has been extended to nitrogen containing heteroaromatic compounds, including indoles and imidazoles.; The construction of benzofurans through the coupling of conjugated dienynes and carbene complex was extended to analogs where the central alkene is replaced by a heteroaromatic ring system. Examples demonstrated include furan, thiophene and imidazole derivatives. A series of heteroaromatic benzofuran derivatives were synthesized in good to excellent yields from the coupling of alkynylheteroaromatic alkenes and carbene complexes. This methodology was employed as the key step for the total synthesis of biologically active natural product egonol.; A novel convergent synthetic route to pyrroles was developed using the coupling of enyne hydrazone with carbene complexes. Various 1,2-disubstituted, 1,2,3-trisubstituted, 1,2,4-trisubstituted and 1,2,3,4-tetrasubstituted pyrroles were synthesized in good yields using this methodology. A tandem pyrrole formation-intramolecular Diels-Alder reaction process was also uncovered.