(±)-cis-4a-alkyl-1,3,4,4a,9,9a-hexahydro-2H-carbazol-2-ones by domino nitro reduction-aza-Michael addition to enones

A domino nitro reduction-aza-Michael addition sequence has been investigated for alpha,beta-unsaturated ketones and compared with the analogous reaction for conjugated esters. As expected, six-membered ring closures of ketones did not proceed as well as for esters (85%) due to the greater inherent reactivity of the ketones. This problem was minimized by performing the cyclization at lower temperature for a shorter time. The process has been extended to a synthesis of (+/-)-cis-4a-alkyl-1,3,4,4a,9,9a-hexahydro-2H-carbazol-2-ones with good yields (65%-86%). While the rigidity of the system and closure of the smaller five-membered ring created some strain in the products, yields were acceptable. The cis ring junction resulted from axial attack to give a more stable chair-like enol that tautomerized to the target heterocycle.

Automated summary

A study was conducted on the domino nitro reduction-aza-Michael addition sequence for ketones and compared with the reaction for esters. The closure of ketones did not perform as well as esters due to their higher reactivity. However, by adjusting the reaction conditions, a synthesis of six-membered ring compounds with good yields was achieved. The products showed some strain, but the yields were acceptable.