A FACILE AND EFFICIENT SYNTHESIS OF THIENO[2,3-C]FURANS AND FURO[3,4-B]INDOLES VIA A PUMMERER-INDUCED CYCLIZATION REACTION

The alpha-thiocarbocation generated from the Pummerer reaction of an o -heteroaroyl-substituted sulfoxide is intercepted by the adjacent keto group to produce an cc-thio-substituted heteroaromatic isobenzofuran. In the presence of a suitable dienophile, the reactive o-xylylene und ergoes a Diels-Alder cycloaddition followed by an acid-catalyzed ring- opening and aromatization to give heteroaromatic naphthalene derivativ es. This one-pot procedure occurs smoothly with electron-deficient die nophiles. The tandem Pummerer cyclization-cycloaddition sequence also occurs intramolecularly using unactivated alkenyl tethers of variable length. With acetylenic dienophiles, the primary cycloadducts undergo in situ ring-opening to produce hydroxynaphthalene derivatives. In the absence of a dienophile, it was possible to prepare 4-(ethylthio)-6-p henylthieno[2,3-c]furan and 1-ethyl-4-(phenylsulfonyl)-4H-furo[3,4-b]i ndole. Various synthetic approaches were used for the preparation of t he requisite thiophene- and indole-derived sulfoxide precursors. The f acility of the tandem Pummerer-Diels-Alder reaction was very dependent on the experimental conditions used to promote the reaction. The best results were achieved by employing a mixture of acetic anhydride and toluene which contained a catalytic quantity of p-toluenesulfonic acid . The presence of the acid effectively drives the reaction in the desi red direction by preventing formation of the acetoxy sulfide, which co rresponds to the normal Pummerer product.