Five-membered rings Cyclopentanones

For example, cyclohexanone is reduced by sodium borohydride 23 times faster than cyclopentanone." The explanation for this difference lies in the relative torsional strain in the two systems. Converting an sp atom in a five-membered ring to sp increases the torsional strain because of the increase in the number of eclipsing interactions in the alcohol. A similar change in a six-membered ring leads to a completely staggered (chair) arrangement and reduces torsional strain. 

The pyrrolidine enamine of cyclopentanone, in which the double bond is exocyclic to two five-membered rings, shows the vinylic proton at 237 Hz (7S). 

Scheme 33 illustrates the difference in reactivity between triazolines obtained from cyclohexanone and cyclo-pentanone enamines. Thus, the reactions of azidophosphonates 239 with cyclohexanone enamines produce unstable aminotriazolines 240 that cannot be isolated due to their spontaneous elimination of amines to provide triazoles 241. Contrary to that, triazolines 242, derived from cyclopentanone enamines, are isolated in good yield (76-88%) and cannot be converted to the corresponding triazoles even by thermolysis <1995H(40)543>. Probably, introduction of a double bond between two five-membered rings would involve too much molecular strain. 

Intramolecular carbene C-H insertion frequently leads to the formation of five-membered rings [967,990,1021,1113-1128], In particular l-diazo-2-alkanones tend to yield cyclopentanones exclusively when treated with rhodium(ll) carboxylates. The use of enantiomerically pure catalysts for diazodecomposition enables the preparation of non-racemic cyclopentane derivatives [1005,1052,1074,1092,1129]. Intramolecular 1,5-C-H insertion can efficiently compete with 1,2-C-H insertion... 

In order for C-alkylation to occur, the p orbital at the a carbon must be aligned with the C—Br bond in the linear geometry associated with the SN2 transition state. When the ring to be closed is six-membered, this geometry is accessible, and cyclization to the cyclohexanone occurs. With five-membered rings, colinearity cannot be achieved easily. Cyclization at oxygen then occurs faster than does cyclopentanone formation. The transition state for O-alkylation involves an oxygen lone-pair orbital and is less strained than the transition state for C-alkylation. 

From four-membered rings An acid-catalyzed transformation has been observed in the conversion of l-[l-methylsulfinyl-l-(methylthio)alkyl]cyclo-butanol to 3-methyl-2-(methylthio)cyclopentanone [9]. - Rearrangement of a /3-lactone to a y-lactone derivative in the presence of magnesiumdibromide [10]. - A borontrifluoride catalyzed cyclobutene to cyclopentene rearrangement [11]. - Ring expansion of a [2+2] photoadduct to a five-membered ring [12]-... 

For example, the faster rate of reaction from of cyclobutanones relative to cyclopentanones can be qualitatively understood on the basis of greater relief of strain in for the four-membered ring versus the five membered ring. Furthermore, since the 1,4-biradical is produced cis and in the singlet state, all of the observed reactions can occur with relatively minor nuclear reorganization and with no prohibitions. 

High diastereoselecivities are normally observed in the alkylation of five-membered ring enolates (eqnations 7 and 8), implying that the alkylation is mainly controlled by steric factors. Thus, with 3-substituted cyclopentanones formation of only the frawi-product (23 and 25, respectively) is preferred. Representative examples are the alkylations of lithium enolates derived from ketones 22 and 24 . Before the electrophiles were added, the enolate solutions were stirred at higher temperature for a longer time to secure the... 

Ring size is crucial with adipic acid, for example, anhydride formation would produce a seven-membered ring, and does not take place. Instead, carbon dioxide is lost and cyclopentanone, a ketone with a five-membered ring, is formed. 

Subsequent work has shown that the presence of an alkyl substituent a to the ketone carbonyl is crucial for the intramolecular five-membered-ring cyclization to occur. Thus, jS-hydroxy cyclopentanones can be synthesized from ketones containing both methyl and cyclopropanol moieties a to the carbonyl by treatment with sodium hydride at 0-25 °C. In the case of phenyl ketone, further retro-aldol ring scission leads to the 1,4-diketone as the only product. A retro-aldol/re-aldol sequence occurs when the methyl substituent is replaced by a longer alkyl substituent, such as an allyl group. In this case, the allyl substituent is located 7 to the carbonyl of the final product. ... 

Enones such as (18) also disconnect to 1,6-dicarbonyl starting materials. Any method of making such compounds is also a potential synthesis of five-membered rings. We have already used this method to convert Diels-Alder adducts to cyclopentanones (Chapter 28). 

Acyclic diazo compounds containing aliphatic chains yield in most cases five-membered rings, e. g., in (8-54) the raAZ5 -cyclopentanone 8.119 is formed diastereo-selectively in 77 9/o yield (Taber and Ruckle, 1986). The diazoketo ester 8.120 containing an alkyl chain with a terminal C = C bond leads to the cyclopentanone 8.121 in 629/o yield (8-55), which demonstrates that the insertion dominates an intra- or inter-molecular cyclopropanation, as found by Wenkert s group (Checcherelli et al., 1990). 

Cyclopentanones and other five-membered ring-containing compounds can be prepared readily by intramolecular C—H insertion of carbenes derived from diazocarbonyl compounds and rhodium(n) acetate. Thus, treatment of the diazoketone 99 with rhodium(II) acetate gave the C—H insertion product 100, used in a synthesis of the toxin muscarine (4.78). 

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