3- Methyl-2-cyclopentenones

Figure 23.4 Intramolecular aldol reaction of 2,5-hexanedione yields 3-methyl-2-cyclopentenone rather than the alternative cyclopropene.

Separation of 3-methyl-2-cyclopentenone from the reaction mixture... 

The resulting solutions ixom above experiments were saturated with sodium chloride and then diethyl ether was added to extract 3-methyl-2-cyclopentenone from aqueous NaOH solution. The diethyl ether in the oiganic phase was then removed by a rotary vacuum evaporator. The heavy cut residue was separated by a simple distillation. The collected 3-methyl-2-cydopentenone was dried over solid anhydrous MgS04 and filtered. 

Transmetallation of silyl enol ethers of ketones and aldehydes with Pd(II) generates Pd(II) enolates, which are usefull intermediates. Pd(II) enolates undergo alkene insertion and -elimination. The silyl enol ether of 5-hexen-2-one (241) was converted to the Pd enolate 242 by transmetallation with Pd(OAc)2, and 3-methyl-2-cyclopentenone (243) was obtained by intramolecular insertion of the double bond and -elimination [148], Formally this reaction can be regarded as carbopalladation of alkene with carbanion. Preparation of the stemodin intermediate 246 by the reaction of the silyl enol ether 245, obtained from 244, is one of the many applications [149]. Transmetallation and alkene insertion of the silyl enol ether 249, obtained from cyclopentadiene monoxide (247) via 248, afforded 250, which was converted to the prostaglandin intermediate 251 by further alkene insertion. In this case syn elimination from 250 is not possible [150]. However, there is a report that the reaction proceeds by oxypalladation of alkene, rather than transmetallation of silyl enol ether with Pd(OAc)2 [151]. 

Compounds I and III at 313 and 238-265 nm photodecompose efficiently to CO and hydrocarbon products (i.e., co = 0.77 and 0.87, respectively). In contrast, compounds II and IV photode-composed much less efficiently under identical conditions. However, compound II photoisomerized efficiently to 3-methyl-2-cyclopentenone. This rearrangement is comparable to the photoisomerization of methylcyclopropyl ketone to methylpropenyl ketone (190). 

Microbial hydroxylation reactions of 2-alkyl-substituted 3-methyl-2-cyclopentenones have also been reported. For example, Aspergillus niger ATCC 9142 and Streptomyces aureofaciens were the most suitable strains for introduction of a hydroxy group in the 4-position of cinerone (23), yielding 60% and 42%, respectively, of cinerolone (24). Analyzed byproducts were 25 and 26369 370. 

The mechanism of intramolecular aldol reactions is similar to that of inter-molecular reactions. The only difference is that both the nucleophilic carbonyl anion donor and the electrophilic carbonyl acceptor are now in the same molecule. One complication, however, is that intramolecular aldol reactions might lead to a mixture of products, depending on which eiiolate ion is formed. For example, 2,5-hexanedione might yield either the five-membered-ring product 3-methyl-2-cyclopentenone or the three-membered-ring product (2-methyl-cyclopropenyl)ethanone (Figure 23.4). In practice, though, only the cycio-pentenone is formed. 

The cage-like intramolecular acetal structures of 77 and 78 attracted my attention, and we synthesized both ( )-77 and ( )-78, the former of which showed the spectral data identical to those of the natural lineatin.33,34 Photocycloaddition of vinyl acetate to 3-methyl-2-cyclopentenone (A) gave B, from which were prepared two isomeric ketones C and D. These were separable by chromatography, and their structures could be determined by -NMR analysis. The ketone ( )-C was further converted to ( )-77, while ( )-D... 

Methyl-6-trimethylsilyloxy-6-vinylbicyclo[3.2.0]heptan-2-one (Table 1, entry 12) is obtained starting with 3-methyl-2-cyclopentenone as enone yield 79% (19 1), recovered enone 10% after chromatography [silica gel (Merck 0.063-0.2 mm), pentane/Et20]. 

NAFION can also Intramolecular cycllze 2,5-hexanedlone to 2,5 dlmethylfuran and 3-methyl-2-cyclopentenone at 150°C In 29 and 2% yield, respectively (41). 

The configuration of the major 1,4-diol isomer from the lithium reduction of 4-hydroxy-2-t-butyl-3-methyl-2-cyclopentenone has been determined " and shows the ring to be almost half-chair in form with a binary axis passing through C-3 and bisecting the C-1 and C-5 segment. 

Scheme 12 Cyclization of acetonylacetone to 2,5-dimethylfuran (acid sites) and 3-methyl-2-cyclopentenone (basic sites)...

The entropic advantages of intramolecularity are particularly noticeable in intramolecular ketone condensations, transformations that provide a ready source of cyclic and bicyclic a,jS-unsaturated ketones. Since ketones can have two enolizable a-carbons, several aldol products may be possible. However, the reversibility of the reaction ensures that usually the least strained ring is generated, typically one that is five or six membered. Thus, reaction of 2,5-hexanedione results in condensation of the terminal methyl (Cl functioning as the enolate carbon) and the C5 carbonyl group to furnish 3-methyl-2-cyclopentenone. 

---