Studies on the Carbon Zip Reaction of 2‐Oxocycloalkane‐1‐carbonitriles

Abstract

As a part of continuing interest in the zip reaction, we present the results on a carbon ring-enlargement reaction of activated ketones with a CN group as a charge stabilizer. Two series of (l-cyano-2-oxocy-cloalky1)alkanoates were prepared from 8and 12-membered cyano-ketones 1 and 2, respectively, namely the propanoates 3 and 4, the butanoates 6 , s and 9 as well as the pentanoates 12 and 15. While treatment with t-BuOK of the former two homologous esters resulted in both ring enlargement and competitive transesterification, the pentanoates 12 and 15 afforded mostly the diastereoisomeric mixtures of bicyclic alcohols 2Oa-c and 31a,b, respectively, which remained intact on further exposure to base. It was shown thatapart from the base used (C-BuOK us. Li(i-Pr),Nthe distribution of products was greatly influenced by the ring size of substrates. This is further illustrated by treatment of ketones 34 and 35 with t-BuOK. While the former rearranged smoothly to diketone 36, no reaction at all took place with the latter. The behavior of the substrates is discussed in terms of steric and energetic reasons.

Amide Activation in Ground and Excited States

“…A good example is found in the literature, where aniline derivatives 37a – c can be deprotonated by NaH or NaOMe, generating their corresponding anion form of 38a – c . The product amide anions 36a – c were formed at elevated temperature ( Figure 15 ) [ 36 , 89 , 90 , 91 ]. During the workup process, an aqueous acid was used to acidify and precipitate the neutral product 39a – c in an irreversible way.…”

Cyclopentenone Annulation of 2‐Oxocycloalkane‐1‐carbonitriles

“…A bicyclic compound similar to 5a,b was obtained only in the case of the 5-membered nitro ketone, while the 8and 12-membered nitro ketones gave products of C, ring enlargement. On the other hand, we have shown [3] that a C, ring enlargement can be realized with an 0x0-carbonitrile analogous to 4a, having a side chain activated only with an alkoxycarbonyl function. In the present work, the unsuccessful ring enlargement of 4a, b is probably due to the weaker electron-attracting ability of the CN group, leading to the irreversible formation of the products 5a, b of aldol condensation.…”

“…The results obtained in the case of the carbon zip reaction [3] were strongly dependent on the ring size of the cycloalkanone and on the length of the alkyl-carboxylate side chain used. With this method, good yields of the C, ring enlargement were observed only for the 8-membered 0x0-carbonitrile.…”

“…Stereoselective catalytic hydrogenation of 5b followed by de-ethoxycarbonylation afforded 14-oxo-cis-bicyclo[l0. 3.0]pentadecane-l -carbonitrile (7). Treatment of 7 with LiN(i-Pr), in THF gave the known synthetic muscone precursor 8 (Scicherrie 2).…”

“…14-0xo-cis-bicyclo/l0. 3.O]pentadecane-l-carboni1rile (7). A mixture of 6 (3.19 g, 10 mmol), NaI (15 g), and AcOH (2.5 ml) in diglyme (25 ml) was stirred under reflux for 1 h. After cooling, H 2 0 (120 ml) was added and the org.…”