Additions to Cyclopentenones

Photo-cycloaddition in the enone (16) yields the adduct (17) which was used as a key step in a new synthesis of stoechospermol. Adduct (18) is formed in high yield on irreuliation of enone (19) in a variety of solvents.  

A detailed report of the reactions of Ar homocubane and homocubane systems has been reported. The key step in the synthetic sequence is the photochemical ring closure of the enone (20) to yield the cage compound (21). The major compound from 

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Additions to cyclopentenones.5 Conjugate addition of cuprates to 4-substi-tuted cyclopentenones can show moderate to high trarw-diastereoselection, which can be attributed to a steric effect. Surprisingly, addition of lithium dimethylcuprate to (R)-5-methoxy-2-cyclopentenone also shows high frans-diastereoselectivity (equation I). The stereoselectivity is decreased somewhat by addition of ClSi(CH3)3. 

Racemic diquinane enone rac-6 was prepared by Piers and Orellana starting from cyclopentenone (Scheme 6) [11]. After the preparation of the heterocuprate from stannane 20, conjugate addition to cyclopentenone in the presence of BF3 Et20 provided carbonyl compound 21. It was expected that conversion of 21 by intramolecular alkylation and subsequent hydrogenation should provide the desired endo-substituted diquinane rac-13. While other hydrogenation methods proved to be rather unselective, reduction in the presence of Wilkinson s catalyst finally resulted in the formation of rac-13 with good facial diastereoselectivity [11]. 

A similar reaction with aldehydes results in y-hydroxy-a,/i-unsalurated acids (66% yield, 1 example). The anion 2 undergoes exclusive 1,4-addition to cyclopentenone and cyclohexenone (yields of products, 67% and 85%, respectively). The anion thus is the equivalent of a -carboxyl vinyl anion. 

OL, -Bifunctionalization of cyclopentenone.1 Although simple ester enolates do not undergo conjugate additions, the enolate of 1 undergoes conjugate addition to cyclopentenone in THF/HMPT (3.3 1) at -20°. This reaction coupled with in situ enolate alkylation provides a notably short synthesis of methyl jasmonate (3). 

Michael additions. Gerlach and Kiinzler report that the lithium enolate of S-t-butyl thioacetate undergoes 1,4-addition to cyclopentenone. They have extended this Michael reaction to a synthesis of methyl jasmonate (5), based on the similar conjugate addition of the trimethylsilyl enolate 1 promoted by tetra-n-butylam-monium fluoride. The adduct 2 was alkylated by l-bromo-2-pentyne in the presence of tetra-n-butylammonium fluoride to give 3 in rather low yield. Remaining steps to 5 were methanolysis and partial hydrogenation of the triple bond. 

J.J.2 Additions to Cyclopentenones and Related Systems - The photophysics of a series of cyclopentenones (12) has been studied. Irradiation in methylene chloride of a solution of the enone (13) and the alkene (14) results in the formation of the adduct (15) in 47% yield. The reaction is best carried out at temperatures around 0°C. The adduct (15) has been converted into the... 

We have already seen examples of cuprates being used in stereochemically controlled conjugate additions to cyclopentenones and similar results can be achieved with ate complexes of vinyl alanes prepared by hydroalumination of alkynes to give e.g. 179 R = hexyl and hence the anti-A-product43 182. 

Additions to Cyclopentenones and Related Systems. (2 + 2)-Cycloadditions are reported following the irradiation of mixtures of alkyl and aryl 2-thioxo-3/f-benzoxazole-3-carboxylates with alkenes. Cycloaddition also occurs to the CS double bond. The photochemical additions of arylalkenes to 3-phenylcyclo-pentenone and 3-phenyl cyclohexenone have been studied. The regio- and stereochemistry observed in the additions has been rationalized in terms of the stability of the intermediate biradicals. Photocycloaddition of allene to the cyclopentenone derivative (6) in methylene chloride solution at — 78°C affords... 

Additions to Cyclopentenones and Related Systems. Bach et al have examined the (2 -H 2)-intramolecular addition within some furanones. Irradiation at... 

Intramolecular Additions to Cyclopentenones - Irradiation (k > 350 nm in THF) of the enone (46) affords a single diastereoisomer identified as (47, 95%). The outcome of the reaction does not seem to be solvent dependent and the same degree of success is obtained with methylene chloride, acetonitrile or methanol as solvents. The corresponding amide also cyclizes efficiently. Crimmins and coworkers have demonstrated that irradiation (X > 350 nm) of the enone (48) results in cycloaddition and the formation of the diastereoisomeric adducts (49) and (50) in a ratio of 83 17. A single product (51) is obtained on irradiation of the related enone (52). These adducts are key intermediates in a synthesis of some spirovetivanes. 

Intermolecular Additions to Cyclopentenones and Related Systems. Mehta and co-workers have described the photochemical addition of 1,2-dichloroethene to the enone (12). This affords the adduct (13), which can be transformed into the protoilludane-type molecule shown in Scheme 4. A further study related to the (2 + 2)-cycloaddition reactions of compounds such as (14) and (15) has determined the crystal structures of these compounds. The... 

In another exan le, o -silyl ester (20) underwent Michael addition to cyclopentenone after deprotonation with LDA (eq 14). The intermediate a-silylatedester enolate of (20) served as a softer nucleophile compared to its unsubstituted analog favoring 1,4- over 1,2-addition. After quenching with allyl iodide the trans-cyclopentanone (21) was obtained. Desilylation with potassium fluoride provided the diene (22). 

Example, 1,4-addition to cyclopentenones (of application in prostaglandin chemistry). 

Aside from Coreys phenylmenthyl propanoate 424, several chiral enolates have been utilized for Michael additions with substantial degrees of diastereoselectiv-ity. Yamaguchi s group developed a series of chiral amide enolates 436 and studied the conjugate addition to crotonates [210]. Another remarkable early contribution came from Oppolzer and coworkers who used dienolate 437 for diastereoselec-tive consecutive additions to cyclopentenone and allylation [211]. The auxiliaries 436 and 437 served for total syntheses of terpenoid natural products. Diastereos-elective Michael additions were also achieved by means of imidazolidinone-based lithium enolate 438 [212] - another showcase of the efficiency of imidazolidinone 118 [54] (Scheme 4.94). 

Another notable example was published by Merck in 2004. The conjugate addition to cyclopentenone, mediated by a leucine-derived chiral auxiliary, resulted in the diastereoselective assembly of two new stereogenic centres (Scheme 11.56). The H.O. cuprate derived from Lipshutz s cuprate in a bottle Li(2-Th)CuCN was found to be superior to a L.O. cuprate reagent previously employed in a similar addition in terms of yield and convenience. 

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