ELECTROPHILIC SUBSTITUTION IN INDOLES .19. FACILE SYNTHESES OF THE 2A,5A-DIAZACYCLOPENTA[J,K]FLUORENE, INDOLO[2,3-A]QUINOLIZINONE AND ASPIDOSPERMA ALKALOID RING-SYSTEMS FROM N-ACYLTRYPTAMINES

Reaction of tryptamine with diketene gave N-[2-(1H-indol-3-yl)ethyl]-3 -oxobutyramide (80%) which with phosphoryl chloride in dichloromethane gave o-5-methyl-2a,5a-diazacyclopenta[j,k]fluoren-3-one 13 (73%). Hyd rogenation gave the 4,5-dihydro and perhydro derivatives. Michael addi tion of ethyl acetoacetate to benzyl acrylate gave 5-benzyl 1-ethyl 2- acetylpentanedioate (57%) which was hydrogenolysed to 4-ethoxycarbonyl -5-oxohexanoic acid (100%), the mixed anhydride of which condensed wit h tryptamine to give arbonyl-N-[2-(1H-indol-3-yl)ethyl]-5-oxohexanamid e 19 (78%). The latter, with trifluoracetic acid anhydride gave (+/-)- cis and trans o-12b-methyl-12H-indolo[2,3-a]quinolizin-4(1H)-one (21 a nd 22) (95%). N-[2-(1-Methylindol-3-yl)-ethyl]piperidin-2-one 31 was s ynthesised in three stages. The anion of 31 with diketene gave (a) ]-3 -(1-oxo-2-methoxycarbonylethyl)-piperidin-2-one 30. Treatment of the d ione 29 with excess of trifluoroacetic acid anhydride gave hyl-5,19-di dehydro-1-methyl-4-oxoaspidospermidine, 34. Reduction of 34 with sodiu m cyanoborohydride gave the 20,21-dihydro derivative 35 and two (+/-)- diastereoisomeric alcohols 36 and 37. Cyclisation of the ester 30 with trifluoracetic acid anhydride gave ro-3-methoxycarbonyl-1-methyl-4-ox aspidospermidine 39.