Cyclopentanones annulation

Whereas lactone annulation invokes a relief of strain of the four membered ring by migration of the ring bond to an electron deficient oxygen, a similar migration to an election deficient carbon creates a cyclopentanone synthesis (Eq. 73). The release of approximately 84 kJ/mole (20 kcal/mole) provides a strong driving force. Thus, the 1,1-cyclobutanone annulation of ketones translates into a 1,1-cyclopentanone annulation. 

For example, an oxaspirohexane <52, readily available by condensing cyclobutanone 61 with dimethylsulfonium methylide, rapidly rearranges (isomerizes) to the cyclopentanone 63 upon exposure to a catalytic amount of lithium bromide55). The high diastereoselectivity of the initial cyclobutanone formation translates into a high diastereoselectivity for cyclopentanone annulation as this example of Eq. 74 demonstrates. 

The vinylcyclopropane rearrangement is particularly valuable for cyclopentane synthesis. Aphidicolin (187), a most unusual antitumor agent, yields nicely to an analysis based on the concept of cyclopentanone annulation as outlined in Scheme 9... 

A concise free radical cyclization process has been applied to the synthesis of new cyclopentanone-annulated azepines 204 from chiral vinylogous amides (Scheme 26). The free radical was generated from the phenylselenide group in 203 (made in turn by N-acylation of 202) using Bu3SnH and l,l -azobis(cyclohexanecarbonitrile) (ACN), as the initiator <2004SL1917>. 

CYCLOPENTANONE ANNULATION VIA CYCLOPROPANONE DERIVATIVES (3a(3.9b)3)-1,2,3a,4,5,9b-HEXAHYDRO-9b-HYDROXY-3a-METHYL-3H-BENZ[ ]INDEN-3-ONE... 

Cyclopentanone Annulation via Cyclopropanone Derivatives cis-3a-Hydroxy-7a-methylbenzinden-l-one. 

Cyclopentanone annulation via a cyclopropoxide anion has great synthetic applicability. Construction of the D-ring in estrone can be achieved by base-induced intramolecular cyclization of an appropriately substituted cyclopropanol using sodium hydride as base (Table 2, entry 23-24 jjjg j-esyit is well accounted for by assuming intramolecular carbonyl addition of a j3-acyl carbanion. 

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