Ene-a-diones, cyclic

The synthesis of halcinonide is summarized in Figure 1, starting with 16a-hydroxy-9a-fluorohydrocortisone (A1 -pregnene-9a-fluoro-llg,16a,17a,21-tetrol-3,20-dione dihydrotriamcinolone, I), which is available commercially.10-13 This tetrahydroxy steroid is slurried in acetone, and then 70% perchloric acid is added slowly. The acetonide, II (9a-fluoro-llg, 16a, 17, 21-tetrahydroxypregn-4-ene-3, 20-dione, cyclic 16,17-acetal with acetone dihydrotriamcinolone-acetonide) precipitates spontaneously from solution. Mesyl chloride is added to the acetonide in pyridine to give the 21-mesylate derivative (dihydrotriamcinolone acetonide-21-mesylate, III). Compound III is dissolved in dimethylformamide, lithium chloride is added and the mixture is refluxed to produce halcinonide (IV), which is recrystallized from a solution of ft-propanol in water. 

Cyclic ketones can also be formed by intramolecular aldol condensation. Roger C. Whitehead of the University of Manchester found (Tetrahedron Lett. 2005,46,2803) that the cis ene dione 4, available by oxidation of the corresponding furan 3, underwent highly diasteroselective aldol condensation, to give untenone A 5. 

Various other [3 + 2] cycloadditions, affording chiral, anellated C6o derivatives with stereogenic centers in the addends are reported in literature. The products were generally obtained as racemates and resulted from reaction of buckminsterfullerene with species like 2,3-disubstituted 2//-azirincs (via nitrile ylides [under direct irradiation] or via 2-azaallenyl radical cations [sensitization by photoinduced electron transfer]),365 1-substituted 5-diazopentane-1,4-diones (via cyclic carbonyl ylides),366 7-alkylidene-2,3-diazabicyclo[2.2.1] hept-2-ene (via a diradicaloid trimethylenemethane derivative),367 1-benzylpy-razolidine-3-ones in the presence of aldehydes (via pyrazolidinium ylides),368 2-trifluoromethyl-2,5-dihydro-l,3-oxazol-5-ones (via nitrile ylides),369 nitro-alkanes in the presence of triethylamine and trimethylsilyl chloride (via N-silyloxynitrones),370 or dv-HOCH2 CH=C H C H 2 OCO 2 H( in the presence of... 

A -Cycloalkene-lA ioiits. a,couple intramolecularly to cyclic ene-l,4-diones in the presence of Cu(acac)2 in benzene at 60°. Other copper catalysts are unsatisfactory. The procedure fails when n is S or 6, but is satisfactory V ien n is 4 and >6. Both cis- and trans-isomers are formed, with the latter predominating exeept when n is 4. The products are reduced by sodium dithionite to cycloalkane-1,4-diones, which can be cyclized by NaOH to fus d-ring cyclo-pentenones when n is 7, 9,10, and 16. 

Until recently, the preparation of the bicyclic ene-diones (47a,b), which are important intermediates in steroid total synthesis, has led only to racemic mixtures This deficiency has now been met as follows. Michael addition of the vinyl ketone (44) to the cyclic diketones (45a) and (45b) afforded the triketo-intermediates (46a) and (46b) in high yield, each containing a prochiral centre. Optically active amines and amino-acids were used as chiral reagents to... 

Michael addition. ° The synthesis of the naturally occurring benz[a]anthraquinones, X-14881 (64 R = Me) and ochrotnycinone (R H) utilizes 2-phenyldithiane anion (Scheme 38), while 11-deoxydauno-mycinone was prepared using 2-methyldithiane. The formation of bicyclo[3.3.0]oct-l(5)-ene-2,6-dione utilizes 2-(2,2-diethoxyethyl)-l,3-dithiane anion. Conjugate addition of the highly stabilized anion (65) occurs readily with enamide (66), whereas the related acyclic anion (67) appears to be less reactive than the cyclic analog (Scheme 39). Conjugate addition of lithiated a-alkylthio monosulfoxide provides a new route for the synthesis of dihydrojasmone. ... 

The study of the Diels-Alder adducts of levopimaric acid has continued with an examination of the structure and stereochemistry of the adducts with cyclopentenone and cyclopent-l-ene-3,5-dione. The major product with cyclo-pentenone is the endo,cis adduct (83). The enedione gives a mixture of enolic endo,cis adducts whose stereochemistry was determined by photocyclisation to give compounds such as (84). A correlation was also achieved with the benzo-quinone adduct through a Favorskii-type ring-contraction of the epoxide (85) to (86). The 13(14) double bond of these adducts is hindered to oxidation, excepting the adduct with acetylenedicarboxylic acid. Condensation of 12-hydroxymethylabiet-7(8)-en-18-oic acid with formaldehyde gives the cyclic ether (87). 

Cyclic acetal with acetone, C H O, /6a. 17-[(1 -methyl-ethylidene)bisioxy)]pregn-4-ene 3,20-dione, algestone aceton-ide, alphasone acetanide, 16l7[Pg.41]

Ring expansion of cyclic a-diketones Resorcinols from cyclopent-3>ene-l,2-diones... 

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