Pyrrolo[2,1-a]isoindol-5-ones and benz[3,4]azocin-1(2H)-1,4,6-triones

Pyrrolo[2,1-a]isoindol-5-ones (8) have been obtained by base catalyzed cyclization and O-alkylation of N-phthalimido-substituted β-keto ester (1) via intermediate (7). Reaction of 1 with MeI/acetone/K₂CO₃ gave the C-alkylation product (3). With bulkier reagents than MeI in a variety of solvents and in the presence of various bases, compounds (8) were isolated. In the absence of an alkylating agent, reaction of 1 with NaH/DMF gave pyrrolo[2,1-a]isoindol-5-one derivative (6), found at room temperature in its keto form (6a) and at higher temperatures in the enol form pyrrolo[2,1-a]isoindol-5-one-1-carboxy-2-hydroxy-3-methyl methyl ester (6b), and 11 which at room temperature already appeared in the enol form. Reaction of acyl chloride (14) with ethyl cyanoacetate/NaH did not stop at ethyl-2-cyano-4-N-isoindol-3-oxopentanoate (15) but proceeded to rearrange to a single diastereomeric benz[3,4]azocin-1(2H)-1,4,6-trione (17).