SYNTHESES AND DIELS-ALDER CYCLOADDITION REACTIONS OF 4H-FURO[3,4-B]INDOLES - A REGIOSPECIFIC DIELS-ALDER SYNTHESIS OF ELLIPTICINE

Seven examples of the novel 4H-furo[3,4-b]indole ring system (3-9)-a stable, synthetic analogue of indole-2,3-quinodimethane-have been synthesized in 6-8 steps from simple indoles in overall yields of 21-28%. These 4H-furo[3,4-b]indoles undergo Diels-Alder reactions with several dienophiles (dimethyl acetylenedicarboxylate, N-phenylmaleimide, benzyne), including ethyl acrylate, which reacts regiospecifically with furoindole 4 to afford a single carbazole ester (59). This result, predicted by molecular orbital calculations, was used to design and execute a regiospecific Diels-Alder synthesis of the antitumor alkaloid ellipticine (63). Thus, the trimethylsilyl triflate-induced reaction between furoindole 4 and dihydropyridone 68b is greater-than-or-equal-to 99% regioselective and affords lactam 70b in 89% yield. Further manipulation gives ellipticine (63) with no detectable (<1%) isoellipticine (64) in the crude product.