Tricyclic enone acetal

In the laboratory of S.C. Welch, the Meyer-Schuster rearrangement was the key step in the stereoselective total synthesis of the antifungal mold metabolite (+)-LL-Z1271a. A tricyclic enone acetal was treated with lithium ethoxyacetylide, and the crude product was exposed to H2SO4 in anhydrous methanol, which brought about the rearrangement and afforded the desired product in 30% yield along with 12% of an epimer. 

To the Co complex (1.28 g, 2.32 mmol) in heptane (23 mL, purged with carbon monoxide for 3 h before use) was added tri-n-butylphosphine oxide (506 mg, 2.32 mmol). The solution was sealed in a screw-cap resealable tub under an atmosphere of CO and heated to 85°C (over glyme heated at reflux) for 71 h. After cooling, the solution was applied directly to a bed of Fluorisil and eluted with ethyl acetate-petroleum ether 95 5 to 50 50) giving the tricyclic enone 304 mg, 45%) as a colorless oil [a]D 22 +116° (c 2.47, CHC13). 

Startg. octalindione treated with 1 equivalent NaBH4 in ethanol to reduce the a,/ -satd. carbonyl, hydrogenated with Pd-on-charcoal in 3 1 ethyl acetate-triethylamine to eliminate the isocyclic double bond, the isoxazole ring hydro-genolyzed with Raney-Ni in ethanol, finally refluxed 7 hrs. with Og-free metha-nolic Na-methoxide then 15 hrs. with aq. 3%-NaOH -> tricyclic enone (startg. m. f. 837). Overall Y 60%. G. Stork and J. E. McMurry, Am. Soc. 89, 5461, 5459, 5463, 5464 (1967). 

The reactions of the lithium enolates of substituted 2-cyclohexenones and 2-cyclopentenones with ( )-l-nitropropene give a mixture of syn- and ami-products3. The lithium enolate of 3,5,5-trimethyl-2-cyclohexenone gives a mixture of the syn- and //-3.5,5-trimethyl-6-(l-methyl-2-nitroethyl)-2-cyclohexcnoncs in modest diastereoselection when the reaction mixture is quenched with acetic acid after. 30 minutes at —78 =C. When the reaction mixture is heated to reflux, tricyclic products are obtained resulting from intramolecular Michael addition of the intermediate nitronate ion to the enone moiety. 

The reaction is very slow in acetic acid alone, and accelerated as acetate by the addition of bases [59]. These two isomers undergo Pd-catalysed allylic rearrangement with each other. 3-Acetoxy-l,7-octadiene (139) is converted to the allylic alcohol 157 and to the enone 158, which is used as a bisannulation reagent [60], Thus Michael addition of 158 to 2-methylcyclopentanedione (159) and aldol condensation give 160. The terminal alkene is oxidized using PdCl2/CuCl/02 to the methyl ketone 161. After reduction of the double bond in 161, aldol condensation affords the tricyclic system 162. 

Tandem cyclizations have also been achieved. For example, the mixed Kolbe oxidation of the functionalized enone 49a in the presence of a fivefold excess of acetic acid afforded tricyclic adduct 52 in yields ranging from 25 to 42% [14] Table 3 shows that low current density favored its formation. However, use of a current density below 25mAcm " resulted in oxidation of the solvent, rather than oxidation of the substrate. 

MQhrle and Herbke " studied the oxidation of the aminocyclohex-enones 276 with the mercuric acetate-EDTA reagent. The primarily formed tricyclic compounds 277 may undergo further oxidation in two positions of the molecule and give compound 278 or/and 279 and 280. Compound 279 (R = H) is easily hydrolyzed to the lactams 280. ... 

The Woodward synthetic route was initiated with a Diels-Alder reaction between 1,4-benzoquinone (14) and diene 15. The cycloadduct 16 formed in this way underwent Meerwein-Pondorff-Verley reduction to afford tricyclic lactone 17 which was converted to bromoether 18. Treatment of this substance with methoxide gave the methyl ether 19. Conversion of 19 to its halohydrin followed by chromium oxidation provided the a-bromo ketone 20 which upon treatment with zinc in glacial acetic acid afforded the bicyclic enone 21. This substance was transformed to the aldehyde-acid 23 by an osmylation-periodate cleavage sequence. The acid function in 23 was es-terified and the aldehyde moiety was condensed with 6-methoxytryptamine. The Schiff base intermediate obtained in this fashion was reduced to give an amine which provided the lactam 24 upon intramolecular acylation. Bischler-Napieralski cyclization of 24 gave the pentacyclic intermediate 25 in which... 

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