Enolates endocyclic

Endocyclic cyclohexanone enolates with 2-alkyl groups show a small preference (1 1-5 1) for approach of the electrophile from the direction that permits the chair conformation to be maintained. ... 

Reacdons of 2-f2-nitrovinyl -l,4-ben2Qquinone with furans, indoles, and endocyclic enol ethers form angular, fused heterocyclic quinoidring systems fsee Eq. 8.13. "... 

Evidently, these or closely related intermediates are accessible and reactive, since the synthesis was successfully achieved as outlined in Scheme 13.28. In addition to the key cationic cyclization in Step D, interesting transformations were carried out in Step E, where a bridgehead tertiary alcohol was reductively removed, and in Step F, where a methylene group, which was eventually reintroduced, had to be removed. The endocyclic double bond, which is strained because of its bridgehead location, was isomerized to the exocyclic position and then cleaved with Ru04/I04. The enolate of the ketone was then used to introduce the C(12) methyl group in Steps F-3 and F-4. 

ENDOCYCLIC ENAMINE SYNTHESIS JV-METHYL- 2- PHENYL- A -TETRA-HYDROPYRIDINE, 54, 93 Enol acetates, acylation of,... 

PREPARATION OF ENDOCYCLIC ENOL ETHERS VIA ALKYNOL CYGLOISOMERIZATION... 

Entry Alkynyl alcohol Endocyclic enol ether Isolated yield Reference... 

XLIV) centers about elaboration of hydroxymethylene ketone (574) into the tricyclic diketone (578). Alkylation of keto nitrile 575 proceeds exclusively cis to the angular methyl groups as does the subsequent reductive methylation. These authors were not able to achieve aldol cycUzation of keto aldehyde 576 and consequently proceeded to enol lactone 577 The addition of a methyl group to 578 could be achieved regioselectively. Subsequently dehydration gave 579 and its endocyclic isomer which were separated chromatographically. 

Alkylation of Enolates Derived from Endocyclic Ketones... 

Enol lactones of carboxylic acids [X = —COR— (to C2) with exocyclic and X = —COR— (to C3) with endocyclic lactones Section VIII]. 

Up to now no reversible photorearrangement of a nonenolizable jS-diketone to an endocyclic enol lactone is known, but several examples of photo-stationary equilibria between j8-diketones and exocyclic enol lactones have been established. After irradiation of either 175 or 176 in benzene a photoequilibrium mixture containing 175 + 176 + 177 is formed with a product ratio 3 95 2.109 With 2-mono- or disubstituted 1.3-indanediones and cis- and frans-alkylidenenaphthalides 43 44,16 it was shown that the ratio of enol... 

Enol ethers and enol acetates of cyclic 1,3-dicarbonyl compounds also afford mixtures of regioisomers on irradiation in the presence of allene, the preferential orientation of addition for enol ethers being mainly head-to-tail.9-11 Endocyclic enol ethers on the other hand, e.g. 2.3-dihydro-4//-pyran-4-ones 4, add regioselectively to allene with exclusive formation of head-to-head adducts.11... 

Several cyclofunctionalization reactions of alkynic alcohols are synthetically useful. Metal ion-promoted cyclofunctionalization of ris-2-propargylcyclopentanol systems proceeds by the 5-exo mode (equation 77 and Table 23).197 Protiodemetallation or reductive demetallation provides the cyclic enol ether in high yields. This method has been used by Noyori in the synthesis of prostacyclin (PGh).197b,197c Reactions with catalytic amounts of mercury(II) or palladium(II) salts gave the endocyclic enol ether as the major product.197 -198 A related cyclization with Ag2C03 has been reported by Chuche.191 Schwartz... 

Cyclization of tran.s-isomcr (4) proceeds more slowly and results in an endocyclic enol ether 5. 

Baldwin, J. E. Kruse, L. I. Rules for ring closure. Stereoelectronic control in the endocyclic alkylation of ketone enolates./. Chem. Soc. Chem. Commun. 1977, 233-235. 

Epoxidation of exocyclic enol lactones. Peracids, even under buffered conditions, are not useful for this epoxidation because of rearrangement and decomposition. Dimethyldioxirane effects epoxidation of y-methylene-y-butyrolactones (1) in 94-96% yield in 2-3.5 hours. It is also effective for epoxidation of endocyclic enol lactones such as 3. 

The reaction of 1-disilagermirene 22 with ketones is similar to the benzaldehyde case. Thus, reaction with butane-2,3-dione gives a final bicyclic product 41, which also has a norbornane type skeleton (Scheme 15, Figure 13)50. Formation of this compound can be reasonably explained by the initial [2 + 2] cycloaddition of one carbonyl group across the Si=Si bond to form the three- and four-membered ring bicyclic compound 42, followed by the isomerization of disilaoxetane 42 to an enol ether derivative 43. The intramolecular insertion of the second carbonyl group into the endocyclic Si—Ge single bond in 43 completes this reaction sequence to produce the final norbornane 41. In this case, C=0 insertion occurred into the Si—Ge bond rather than the Si—Si bond, which is reasonable due to the weakness of Si—Ge bond. 

Exocyclic enol ethers.1 A route to (E)-cyano- or -methoxycarbonyl substituted exocyclic enol ethers involves hydrogenation and isomerization catalyzed by Pd/C of an endocyclic dienol ether. Thus hydrogenation of la or lb in toluene at - 35° catalyzed by Pd/C gives (E)-2a or 2b as the major product in about 80% yield. 

For weak acids, the proton is directly transferred from the acid to the substrate in a reagent-controlled manner and, in order to increase the selectivity, extremely shielded 2 -substituted m-terphenyls have been developed as concave protonating reagents inspired by the geometry of enzymes. Thus, the diastereoselective protonation by a series of substituted phenols of endocyclic keto enolates, obtained by the stereocontrolled 1,4-addition of lithiocuprates onto substituted cyclohexenones, was reported by Krause and coworkers354 355 and applied to the synthesis of racemic methyl dihydroepijasmonate356. 

On the other hand, lithium enolates derived from substituted endocyclic ketones have largely been exploited in the synthesis of steroids since the regioselectivity of their deprotonation can be controlled and high levels of 1,2- and 1,3-stereoselection occur9,418. The control is steric rather than electronic, with the attack directed to the less substituted ji-face of the enolate for conformationally rigid cyclopentanones, whereas stereoelectronic control becomes significant for the more flexible cyclohexanones. Finally, an asymmetric variant of the formation of a-branched ketones by hydration of camphor-derived alkynes followed by sequential alkylation with reactive alkyl halides of the resulting ketones was recently reported (Scheme 87)419. 

In recent work Coates, Mason and Shah have successfully achieved the synthesis of gymnomitrol (29Ja).280) Since intramolecular aldol condensation of the aldehyde obtained by hydrolysis of 291 (Scheme 45) was unfavorable, conversion to enol lactone 292 was effected. Dibal-H reduction of 292 resulted directly in aldoli-zation of the intermediate lactol, oxidation of which afforded 293. The latter was converted successfully to keto alcohol 294 by capitalizing on the different steric environments about the carbonyl groups. Sequential dehydration and hydride reduction of 294 gave a 45 55 mixture of exo and endocyclic isomers 295a and295 b which were separated by TLC. 

The quaternary center was constructed stereospecifically by Claisen rearrangement (Scheme 46). The necessary enol ether was obtained by reaction of the secondary alcohol of 399 with ethyl vinyl ether and mercuric acetate. To change the polarity of the endocyclic double bond, the unsaturated ketone was reduced with lithium aluminum hydride to the allylic alcohol, 400, at low temperature. Then, prolonged heating with xylene led to the aldehyde, 401. Protection of the secondary alcohol was achieved by bromoether formation with W-bromosuccinimide in acetonitrile before the aldehyde of 402 was reacted with methyllithium. The epimeric mixture of secondary alcohols was protected as acetates 403. Then, the cyclic ketone... 

Subsequent hydroboration of endocyclic enol ether 5 proceeded stereoselectively to give alcohol 6, which was further oxidized with tetra- -propylammorrirrm perrutherrate (TRAP) and A-me% lmorpho-line 7V-oxide (NMO) (Ley et al. 1994) to afford ketone 7. Oxidative removal of the /r-methoxyberrzyl (PMB) group followed by treatment with ethanethiol and zinc triflate effected cyclization of the D-ring... 

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