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Joined 2026-09-21 Message
Incoming links: Cyclopentane
Past exam of the chemistry B course of the University of Cambridge 2025 Paper 1 B2 c Solution 2026-10-20
Base deprotonates the sulfonamide. Its nitrogen attacks one epoxide carbon from the back, breaking the C–O bond at that carbon and producing an adjacent alkoxide. The nitrogen and oxygen attachments on the cyclopentane are therefore trans. The alkoxide then attacks the aromatic carbon bearing the fluorine ortho to the sulfonyl group. Intramolecular nucleophilic aromatic substitution expels fluoride and closes a seven-membered heterocycle with the path . The para fluorine remains.
This tandem epoxide-opening/ring-closing pathway is required by the formula of F: simple epoxide addition would retain both fluorines, whereas F contains only one. In the second stage, pyrrolidine replaces the remaining para fluorine by another nucleophilic aromatic substitution, producing G. The mass balance is F plus pyrrolidine minus HF, as required by the given formula of G.
The left ring system is spiro, and the right-hand substituent is , not OMe directly attached to the cyclohexene ring. Let denote the right cyclohexenyl group bearing that methoxyethyl substituent cis to its linker. The connection to the left alkene carbon is . These observations suggest two Diels–Alder constructions. A left-hand dienehas the original cyclopentane carbon as one terminal diene atom; cycloaddition with an ethylene equivalent gives the spiro six-membered ring. Its residual double bond is between the two internal diene atoms, putting the linker on the required alkene carbon.
Build and its four-carbon alcohol appendage first. Protect the OH group of the indicated 4-Bromobutan-1-ol, for example as a THP ether. Convert the primary bromide to its grignard reagent and formylate with DMF, giving . olefination with an allylidenetriphenylphosphorane, , supplies a conjugated diene ; select the required diene geometry rather than assume a single E/Z outcome.
Cycloaddition with methyl vinyl ketone produces a cyclohexene with a protected four-carbon alcohol chain at one saturated ring carbon and an acetyl group at its adjacent ring carbon. Choose and isolate the adjacent-substituent cis regioisomer, matching the two dashed substituent bonds in the target. Endo preference and diene geometry can aid the selection, but an unsymmetrical diene is not guaranteed to give a unique regioisomer. Reduce the acetyl ketone to , then methylate that alcohol with sodium hydride/methyl iodide while the chain-end OH is protected. Remove the THP group under mild acid conditions to reveal , preserving the secondary methyl ether and the ring alkene.
Oxidize this primary alcohol to . Add vinylmagnesium bromide to give , then oxidize the allylic alcohol to the enone . This carbonyl carbon is the original alcohol-end carbon of 4-bromobutanol; after olefination it will be the linker-bearing carbon of the left ring alkene.
In the other branch, reduce the specified cyclopentanone to cyclopentanol, convert to bromocyclopentane, and react with triphenylphosphine to obtain the cyclopentylphosphonium salt. Deprotonation gives the cyclopentylidene phosphorane, whose ylidic carbon is part of the five-membered ring. Wittig olefination of the just-prepared enone gives the substituted diene displayed above. This carbonyl–ylide pairing keeps the ring carbon terminal in the diene and avoids accidentally constructing a fused ring instead of a spiro ring.
Finally, cycloadd an ethylene equivalent. Ethylene itself requires suitably forcing/high-pressure conditions; a more reactive alternative is phenyl vinyl sulfone, followed by reductive removal of the sulfone substituent using a method compatible with the methyl ether and retained C=C bonds. The latter installs the same two otherwise unsubstituted saturated carbons. Control or separate any additional cycloaddition isomers, and retain the previously selected cis configuration on .
The carbon count provides a strong check: cyclopentanone supplies five, bromobutanol four, DMF formylation one, the first allylidene ylide three, methyl vinyl ketone four, O-methylation one, vinylmagnesium two, and the final ethylene equivalent two, totalling 22 target carbons. Three original bromobutanol carbons form the linker; its fourth becomes the substituted carbon of the spiro ring's alkene. The proposal is a multistep constitutional/relative-stereochemical route with explicit regioisomer and diastereomer selection, not an unsupported claim of a single quantitative cycloaddition product.
