Synthesis of spirocyclic carbazole- and acridine-lactams

Abstract

Spirocyclic carbazole- and acridine-lactams were prepared by Fischer-indole or Friedländer-quinoline synthesis starting from spirocyclic ketones with a lactam ring. All annulation products were obtained as mixtures of separable regioisomers, which differ only in the position of one methyl group. The starting materials were prepared from 2-pyrrolidone and 2-piperidone by a sequence of protection (by N-allylation), alpha-acylation, iron-catalyzed Michael reaction followed by Robinson-annulation, palladium-catalyzed N-deprotection and catalytic hydrogenation. The overall yields of this six-step sequence are 13 and 17%, respectively, and the racemic ketones are obtained as single diastereoisomers.

Iron Catalysis in Organic Synthesis

“…Christoffers et al applied their conditions for the iron-catalyzed Michael addition to the synthesis of lactam precursors which could be converted into spirocyclic tetrahydrocarbazoles and tetrahydroacridines by Fischer indole or Friedländer quinoline synthesis, respectively (Scheme ) …”