Tandem Michael addition–[3,3]sigmatropic rearrangement processes. Part 2. Construction of cyclopropa[3,4]pyrrolo[3,2-e]indol-4-one (CPI) unit of antitumour antibiotic CC-1065

Abstract

Development of an alternative strategy for preparing 3-acetoxymethyl-2,3-dihydro-1-methylsulfon-yl-6-methoxyindole 25 has been completed. Since 25 was an intermediate in a previous synthesis of the CPl unit 5 of the antitumour antibiotic CC-1065 1, this achievement constitutes a formal synthesis of the racemic compound 5. The key strategic element of the approach involves the tandem Michael addition–[3,3]sigmatropic rearrangement process of methyl propiolate 10 and benzyl N-hydroxy-N-(3-methoxyphenyl)carbamate 9, prepared from m-nitroanisole 19, to furnish indole 8 as the sole product. Subsequent elaboration of compound 8 into indoline 25 was then achieved by applying Cava's technique. The conversion of 25 into 5 was also demonstrated on the basis of the well-established, Wierenga's procedure.