IMDAF cycloaddition as a method for the preparation of pyrrolophenanthridine alkaloids

Acylation of 5-amino-2-furancarboxylic acid methyl ester with alkenoyl acid chlorides gives 2-amidofurans that undergo intramolecular Diels-Alder cycloadditions. The reactions occur at 165 degrees C in toluene or at 100 degrees C when 4 M ethereal LiClO4 was used as the solvent. The resultant dihydroindoles are formed by the nitrogen lone pair assisted ring opening of the initial era-bridged cycloadducts, followed by loss of water. Under certain conditions, alternative cationic cyclization routes become important pathways. Several members of the pyrrolophenanthridine class of alkaloids were obtained by a short, efficient method based on the intramolecular Diels-Alder furan cycloaddition of 2-amidofurans containing a tethered alkenyl group. The resulting dihydroindoles were elaborated in one step to the 1H-pyrrolo[3,2,1-de]phenanthridine ring system by a free radical induced cyclization using bis(tributyltin).