2- Methyl-3-cyclopentenone

The anion of (Zs)-4-(diphenylphosphinyl)-6-methyl-2-heptene undergoes addition to 2-cyclopentenone and 2-methyl-2-cyclopentenone to give predominately yn-adducts3. 

This type of asymmetric conjugate addition of allylic sulfinyl carbanions to cyclopen-tenones has been applied successfully to total synthesis of some natural products. For example, enantiomerically pure (+ )-hirsutene (29) is prepared (via 28) using as a key step conjugate addition of an allylic sulfinyl carbanion to 2-methyl-2-cyclopentenone (equation 28)65, and (+ )-pentalene (31) is prepared using as a key step kinetically controlled conjugate addition of racemic crotyl sulfinyl carbanion to enantiomerically pure cyclopentenone 30 (equation 29) this kinetic resolution of the crotyl sulfoxide is followed by several chemical transformations leading to (+ )-pentalene (31)68. 

The 2-methylenecyclopentanone initially formed presumably rearranges into 2-methyl-2-cyclopentenone under the reaction conditions. The final step of the mechanism, elimination of the cobalt carbonyl group, is not well understood but the same kind of elimination and reduction reactions occur with known 3-ketocobalt complexes. As mentioned above, crotonaldehyde, acrolein (27), and glyddaldehyde (38) react rapidly with cobalt hydrocarbonvl under similar conditions to give reduction products, rather than forming stable alkyl- or acyl-cobalt tetracarbonyl derivatives. 

A total synthesis of ( )-aromatin has utilized the lithium anion of the dithiane of (E)-2-methyl-2-butenal as a functional equivalent of the thermodynamic enolate of methyl ethyl ketone in an aprotic Michael addition (Scheme 189) (81JOC825). Reaction of the lithium anion (805) with 2-methyl-2-cyclopentenone followed by alkylation of the ketone enolate as its copper salt with allyl bromide delivered (807). Ozonolysis afforded a tricarbonyl which cyclized with alkali to the aldol product (808). Additional steps utilizing conventional chemistry converted (808) into ( )-aromatin (809). 

The chiral organocopper compound (186) adds diastereoselectively to 2-methyl-2-cyclopentenone, allowing the preparation of optically active steroid CD-ring building blocks (Scheme 68).202-204 A related method was applied to a synthesis of the steroid skeleton via an intramolecular (transannular) Diels-Alder reaction of a macrocyclic precursor.203 Chiral acetone anion equivalents based on copper azaeno-lates derived from acetone imines were shown to add to cyclic enones with good selectivity (60-80% ee, after hydrolysis).206-208 Even better ee values are obtained with the mixed zincate prepared from (187) and dimethylzinc (Scheme 69). Other highly diastereoselective but synthetically less important 1,4-additions of chiral cuprates to prochiral enones were reported.209-210... 

Protons a to a carbonyl group or y to an enone carbonyl group are acidic (Problem 22.37). Thus for 2-methyl-2-cyclopentenone, protons at the starred positions are acidic. 

Propose a synthesis of 1 starting from 2-methyl-2-cyclopentenone. 

Friedel-Crafts acylation. Posner el al. have developed a remarkably efficient route to the methyl ether of the steroid 11-oxoequilenin (5) from 2-methyl-2-cyclopentenone (1). jS-Addition of the organocoppermagnesium reagent 2 to 1 followed by a-alkylation with ethyl iodoacetate proceeds stereospecifically to give the secosteroid 3 in 94% yield. The final step requires an intramolecular Friedel-Crafts acylation, a reaction that has proved troublesome in previous syntheses of steroids via 9,11-secosteroids. And indeed attempts to cyclize the free acid corresponding to 3 with HF proceeded in yields of 10%. However, cyclization of the ketal acid 4 gives stereochemically pure 5 in 75% yield based on recovered secosteroid. The overall yield from 2-bromo-6-methoxynaphthalene is 52%. 

The butyllithium-generated anion of an allylic sulfone was reported to add to conjugate enones, but different regioselectivity was observed for 2-cyclohexenone (1,4-y) and 3-penten-2-one (1,4-a), as shown in equation (31). Clean 1,4-a additions to both acyclic and cyclic enones can be realized when the lithio carbanions are allowed to react in the presence of HMPA (2 mol equiv.) at -78 C. Under these conditions, allyl phenyl sulfone reacts with 2-cyclohexenone. 2-methyl-2-cyclopentenone and 3-methyl-2-cyclohexenone, giving the corresponding 1,4-a adducts as a 75 25 mixture of two dia-stereoisomers. In the reaction of allylic phenyl sulfone with an acyclic enone, 4-methyl-3-penten-2-one,... 

A ketone with a substituent group in its p position might be prepared bys conjugate addition of that group to an ,/3-unsaturated ketone. In the present instance, the target molecule has a propyl substituent on the j3 carbon and might therefore be prepared from 2-methyl-2-cyclopentenone. 

Reaction of an a-(phenylthio)nitrile with base, such as LDA, followed by an aldehyde or a ketone gives a 1,2-addition product in good yield, while the use of a, -unsaturated aldehy s and ketones usually leads to the 1,4-addition product. Conjugate addition of the a-(phenylthio)acetonitrile anions to 2-methyl- or 2-phenyl-2-cyclohexenones or 2-methyl-2-cyclopentenones, followed by acid quenching under kinetic control, leads to different ratios of cis and rr[Pg.561]

Mixed acid-base ion-exchange resins.1 Rexyn ion-exchange resins (Fisher Scientific Co.) consist of sulfonic acid beads and quaternary ammonium hydroxide beads. Stowell and Hauck1 have used such a resin to convert the keto acetal 1 in one operation to 2-methyl-2-cyclopentenone-l (2). Two steps are involved acid-catalyzed hydrolysis of the acetal group and base-catalyzed aldol condensation. The first step is reversible, but the second is irreversible. 

Methyl-2-cyclopentenone is also efficiently hydrogenated affording (7 )-2-methylcy-clopentanone47. On the other hand, only 5% of the corresponding 2-ethyl-substituted substrate is transformed under the same conditions and no transformation is observed if the substrate bears a methyl substituent at C-347. 

Similar results have also been obtained with Currularia hmata as the biocatalyst48. (R)-2-Methylcyclopentanone was formed from 2-methyl-2-cyclopentenone in 95% yield however, the optical purity remained low (29% ee). 

The synthesis of ( )-integertimine (23) required a much longer procedure. Firstly, the acid portion of integerrimine was synthesized by Narasaka and Uchimaru from 2-methyl-2-cyclopentenone... 

Posner and co-workers have developed an efficient (52% overall yield) conversion of 2-methyl-2-cyclopentenone into ( )-ll-oxoequilenin methyl ether, 4 (Scheme 1). TTie latter had been hydrogenolyzed earlier to equilenin methyl ether by Birch (see Volume 2, p. 660). 

An ethereal soln. of 3-ethynyl-2-methyl-2-cyclopentenone added dropwise to startg. organocuprate in ether at —78", and quenched with satd. aq. NH4CI after 1.5 h product. Y 93% (34 1 Z E). F.e. and cuprates, also 1,6-addition of PhSLi (to give the E-isomer), s. M. Hulce, Tetrahedron Letters 29, 5851-4 (1988). 

Allyl /3-keto carboxylates and allyl enol carbonates undergo a palladium-catalyzed decarboxylation-dehydrogenation to yield o, S-unsaturated ketones in usually high chemical yield and with good selectivity. Following this approach, it was possible to obtain 2-methyl-2-cyclopentenone in two steps from diallyl adipate in a procedure that could be convenient for large-scale preparations (eq 62). ... 

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