1,4-Conjugate addition seven-membered rings

Disconnection of the bicyclic diketone 21 starts reasonably to reveal 22 but the two carbonyl groups are now 1,6-related suggesting a reconnection strategy (chapter 27). But this is impossible as the bridgehead alkene 23 is too strained to exist. However, if we extrude the carbon atom in the seven-membered ring between the ketone and the branchpoint 22a, we get a new ketoester 24 with a 1,5 relationship that can be made by conjugate addition (chapter 21). 

As illustrated in Equation (1), a Lewis acid-promoted intramolecular conjugate addition of a furan to a dienone was used to generate the seven-membered ring of the fused tricyclic framework of sesquiterpene echinofuran <2003T1877>. The use of Et2AlCl provided the best result, minimizing undesired polymerization of the furan substrate 3. 

The reaction with EtAlCb is a Lewis-acid-catalysed conjugate addition of the allyl silane on to the enone. Conjugate addition is preferred because the nucleophile (allyl silane) is tethered to the electrophile (enone) and the five-membered ring is easier to form than the alternative seven-membered ring. 

Aryl iodides are more reactive towards oxidative addition than aryl bromides, and a selective Heck coupling (without phosphine ligands) with an unsaturated side chain left the bromide in place. A second Heck reaction of this bromide with an allylic alcohol was used to introduce a second side chain. Cyclization of the amide on to the allylic alcohol was achieved with palladium catalysis, not as might have been expected with palladium(O) but instead with palladium(ll), to produce the seven-membered ring. Finally, the conjugated double bond was reduced and the sulfonamide removed under photolytic conditions. 

Annelation-ring cleavage.1 A bifunctional reagent with an acetal and an allylsi-lane group can be used for annulation of silyl enol ethers to six- and seven-membered carbocycles (equation I).2 The reaction involves conjugate addition to give an adduct that undergoes intramolecular cyclization. 

There are a handful of examples where amino acids with ring sizes of seven members and larger have been prepared using the carboxyl refunctionalization reaction just shown. Reaction of anhydride 7.29H with ammonia, for example, gave amide-acid 7.30. Hofmann rearrangementl of the amide led to cfs-2-aminocyclo-heptane-1-carboxylic acid, 731. An alternative synthesis conjugate addition of ammonia to cycloheptenecarboxylic acid, 7.32. This reaction gave rra/is-2-amino-cycloheptane-1-carboxylic acid, 7.33. 

It can be seen that for C H systems with m > 4 regardless of the size of the ring four infrared-active normal vibrations and seven Raman-active ones are to be expected. Since the members of the series with m = 3 and 4 are known only with phenyl substituents or in complexes, it is impossible to observe their n.v. unaffected by conjugation or complex bonding effects. However, for the higher members, it suffices for establishing structures to find spectra with only a few bands, namely the four IR- and seven Raman-active ones. In addition. Table II shows that the rule of mutual exclusion is strictly valid, although Ds and do not have a center of inversion. 

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