Cyclopentenones from allylic alcohols

The formation of 1,1-dichlorocyclopropanes from allylic alcohols is of particular synthetic value because the initial adducts can undergo rearrangement under acidic conditions to give good yields of cyclopentenones (see Eq. 2.37) [55]. This result is of mechanistic interest as well since alcohols react with dichlorocarbene to yield the corresponding chloride and carbon monoxide. This reaction is discussed in Chapter 3. In the case of allylic alcohols, dichlorocarbene prefers to react at the carbon-carbon double bond rather than at the hydroxyl function. 

A bis-annulated carbohydrate has been reported by Pipelier and Ermolenko [368] in their synthetic route to quadrone. This complex stmcture was elaborated from levoglucosan by two successive branchings of allyl groups at C2 and C4 using epoxide opening methodology. A keto group, formed from the alcohol at C3, allowed initial cyclopentenone constmction. Further manipulation of this ketone allowed a second Robinson annulation to form the second fused six-membered carbocycle. 

The starting material for iloprost is the enantiomerically pure Corey lactone, which is treated with the lithium salt of ethyl acetate. After oxidation, treatment with l,5-diazabicyclo[4.3.0]non-5-ene (DBN) leads to an exceptionally interesting rearrangement. Presumed cleavage of the cyclic ether generates an enolate, which adds to the cyclopentenone in a Michael reaction. Decarbethoxylation is achieved with l,5-diazabicyclo[2.2.2]octane (DABCO), and the w-chain is constructed under Horner-Wadsworth-Emmons conditions. The subsequent reduction leads to a mixture of allyl alcohols, which can be purified by chromatography, and the alcohol from the less polar product then be released by trans-esterification. Both alcohol functions are then protected as THP-ethers. The... 

The dichlorocyclopropanes (391 R R, R = H, alkyl), readily obtained from the corresponding allylic alcohols by the Makosza procedure, rearrange on heating with hydrobromic acid to the cyclopentenones (392). This sequence has been applied (Scheme 34) to the preparation of the bicyclic ketone (393), a versatile intermediate in the synthesis of pyridomuscone, muscone, and [10]metacyclophane. ... 

Interestingly, reaction of diphenylketene with spirocyclic azanorbomene 34, prepared by the method of Grieco et al. [1] from spirocyclopropyl-cyclopentadiene and benzyliminium ion in 62% yield, results in the formation of an unstable tricyclic intermediate 35, which upon workup gives allylic alcohols 36 in 51% yield (Scheme 2.3) [13]. A single cyclopentenone derivative... 

Vinyl epoxides 372 and 373 are converted to conjugated dienes 375 and 378 via the 7T-allyl intermediates 374 and 377. In other words, different protons are eliminated, depending on the structure to give either the cyclopentenone 376 or the dienyl alcohol 378. The unsaturated ketone 376 is an expected product, because elimination of a hydride from the carbon connected to oxygen is common [171]. 

A similar Nicolas-Pauson-Khand combination was used in a synthesis of the ketone analogue of biotin 7.98, required for biochemical studies (Scheme 7.25). In this case, the Nicholas reaction was intermolecular, between allyl thiol as the nucleophile and carbocation 7.94 generated from alcohol 7.93. The Pauson-Khand reaction was then between the dicobalt complexed alkyne 7.95 and the double bond from the thiol moiety. The Pauson-Khand reaction proceeded with no stereoselectivity, and the diastereoisomers had to be chromatographically separated at a later stage. The synthesis was completed by reduction of the alkene of cyclopentenone 7.96, without using palladium-catalysed hydrogenation due to the sulfide moiety, and ester hydrolysis. 

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