An efficient, PIFA mediated approach to benzo-, naphtho-, and heterocycle-fused pyrrolo[2,1-c][1,4]diazepines.: An advantageous access to the antitumor antibiotic DC-81

The synthesis of a series of optically pure benzo-, naphtho-, and heterocycle-fused pyrrolo[2,1-c]-[1,4]-diazepin-5,11-dione derivatives starting from L-proline methyl ester is presented. The synthetic plan includes an aroylation step at the proline nitrogen followed by transformation of the ester residue into a N-methoxyamide group. The subsequent key cyclization step embraces the PIFA mediated formation of a N-acylnitrenium intermediate and its succeeding intramolecular trapping by the aromatic ring. The presented general approach solves the need of starting from not very accessible amino (or a related functionality) aromatic starting materials, and its effectiveness is demonstrated in the synthesis of the antitumor antibiotic DC-81.