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Joined 2026-09-21 Message
Incoming links: Masked carbonyl
Use the nitro group as a masked carbonyl and a carbon nucleophile. The most informative disconnection reverses the six-membered aldol annulation. Before that closure, the cyclopentanone beta carbon bearsThe carbon carrying will become the lower carbonyl of the final six-membered ring by a Nef reaction. It comes from the specified nitromethane. The remote methyl ketone supplies the upper methyl-substituted alkene carbon after aldol condensation.
First, use a mild base to generate a nitromethane-derived nitronate and add it conjugatively to the indicated cyclopent-2-en-1-one. Protonation gives 3-(nitromethyl)cyclopentanone. Deprotonate its nitromethyl group and perform a second Michael addition to methyl vinyl ketone, giving . The nitro-stabilized carbon is appreciably more acidic than a simple ketone alpha carbon, permitting selective nitronate formation; control the acceptor stoichiometry to avoid a further Michael alkylation of the remaining nitro-bearing H.
Form the enolate/enamine at the cyclopentanone carbon between its carbonyl and the side-chain-bearing carbon. Intramolecular attack on the remote methyl ketone closes a six-membered ring; the two shared atoms are the original enone alpha and beta carbons. Hydrolysis if required and dehydration create the alkene between the original alpha carbon and the newly formed tertiary carbinol carbon. That carbinol carbon retains its methyl substituent, placing the methyl exactly as required. The original cyclopentanone carbonyl remains the carbonyl of the five-membered ring.
Finally, form the secondary nitronate and carry out controlled acidic Nef hydrolysis to replace its unit by . The resulting fused product contains the two required ketones. Carrying out the annulation before exposing this second ketone reduces competing enolate/aldol pathways that would be available in the corresponding triketone. The nitro intermediate's competing deprotonation means that the aldol step needs conditions designed to access the ring carbonyl enolate/enamine; simply treating every carbonyl position as equally reactive would not establish the route.
The carbon ledger is from cyclopentenone, from nitromethane and from methyl vinyl ketone, giving the nine-carbon fused skeleton plus its methyl substituent. A primary-nitro Nef reaction performed before the second carbon alkylation would instead give an aldehyde and would lose this useful protected-carbonyl construction.
