L,4-dien-3-ones

A variety of conjugated dienones are reduced by lithium-ammonia, presumably via dienyl carbanions analogous to the allyl carbanions encountered in enone reductions. Cross-conjugated l,4-dien-3-ones afford 4-en-3-ones as the major reduction products, indicating that the cyclohexadienyl carbanion (55) protonates largely at C-1. Some protonation at C-5 does occur as shown by examination of the NMR spectrum of the crude reduction product derived from the 17-ethylene ketal of androsta-l,4-diene-3,17-dione. The 17-ethylene ketal of androst-4-ene-3,17-dione is formed in 75%... 

An illustration of the difference in reactivity of a-and / -halides is provided by the ready elimination of 1,4a-dibromo-5a-cholestan-3-one to 4a-bromo-5a-cholest-l-en-3-one in collidine at room temperature. Calcium carbonate in refluxing DMA is necessary to complete the dehydrobromination to the l,4-dien-3-one. ... 

The direct reaction of androsta-l,4-diene-3,17-dione with acetylene in the presence of potassium t-amyloxide gives the 17a-ethynyl-17j -hydroxyandros-ta-l,4-dien-3-one in only 12% yield. 

This nitrite (5 g) is dissolved in 200 ml of toluene and photolyzed For 2 hr at 20° as described above. Without further treatment the solution is chromatographed on 100 g of alumina and eluted with methylene dichloride containing increasing proportions of methanol. The first fraction gives 0.6g prednisolone BMD. The latter fractions afford 17,20 20,21-bismethylenedioxy-llj5-hydroxy-18-oximinopregna-l,4-dien-3-one (3 g) mp 270-274° [oc]d 0°, after crystallization from ethyl acetate-hexane. 

Tiifluoromethyl derivatives of tetrahydrothiopyran-4-ols result from the Michael addition of hydrosulfide to a, -unsaturated trifluoromethyl ketones <96JOC1986> and tetrahydro-thiopyran-4-ones arise from the reaction of H2S with l,5-diaryl-2-chloropenta-l,4-dien-3-ones <96PS(108)93>. 

An unusual reaction was been observed in the reaction of old yellow enzyme with a,(3-unsat-urated ketones. A dismutation took place under aerobic or anaerobic conditions, with the formation from cyclohex-l-keto-2-ene of the corresponding phenol and cyclohexanone, and an analogous reaction from representative cyclodec-3-keto-4-enes—putatively by hydride-ion transfer (Vaz et al. 1995). Reduction of the double bond in a,p-unsaturated ketones has been observed, and the enone reductases from Saccharomyces cerevisiae have been purified and characterized. They are able to carry out reduction of the C=C bonds in aliphatic aldehydes and ketones, and ring double bonds in cyclohexenones (Wanner and Tressel 1998). Reductions of steroid l,4-diene-3-ones can be mediated by the related old yellow enzyme and pentaerythritol tetranitrate reductase, for example, androsta-A -3,17-dione to androsta-A -3,17-dione (Vaz etal. 1995) and prednisone to pregna-A -17a, 20-diol-3,ll,20-trione (Barna et al. 2001) respectively. 

Using this procedure, however, the authors have also prepared tricyclic compounds such as 1-87 in high yield starting from l,4-diene-3-ones 1-84 containing an electron-rich arylethyl side chain. Probable intermediates are 1-85 and 1-86 (Scheme 1.23) [24]. 

West and coworkers developed two new domino processes in which a [4+3] cycloaddition (Nazarov electrocyclization) of l,4-dien-3-ones is succeeded by either an... 

Two type la syntheses of (3-hydroxypyrroles have appeared. An aza-Nazarov cyclization of l-azapenta-l,4-dien-3-ones produced (3-hydroxypyrroles including 2,2 -bipyrroles <06EJO5339>. A second approach to a (3-hydroxypyrrole involved an intramolecular N-H insertion into a rhodium carbene derived from the decomposition of a diazoketone <06JOC5560>. On the other hand, the photochemical decomposition of the diazoketone led to pyrrolidin-2-ones. 

A stoichiometric double C-H functionalization mediated by an iridium ketene complex leads to l,4-dien-3-ones,... 

Comparison with the reported reactivity of the spiro[2.5]octa-l,4-dien-3-one 110 and 4-(hexafluoroisopropylidene)cyclohexa-2,4-dien-l-one 111 have suggested that the conjugated cyclopropane ring of compounds 108 and 109 imparts a strong acid dependence to its reactivity with nucleophiles, Eq. (45). This property is likely to be relevant for the exceptional reactivity of these antibiotics toward DNA [148]. 

The 17-ethylene ketal of androsta-l,4-diene-3,17-dione is reduced to the 17-ethylene ketal of androst-4-en-3,17-dione in about 75% yield (66% if the product is recrystallized) under the conditions of Procedure 8a (section V). However, metal-ammonia reduction probably is no longer the method of choice for converting l,4-dien-3-ones to 4-en-3-ones or for preparing 5-en-3-ones (from 4,6-dien-3-ones). The reduction of l,4-dien-3-ones to 4-en-3-ones appears to be effected most conveniently by hydrogenation in the presence of triphenylphosphine rhodium halide catalysts.15,25 Steroidal 5-en-3-ones are best prepared by base catalyzed deconjugation of 4-en-3-ones.65,72a... 

Preparation of 17/3-hydroxyandrosta-l,4-dien-3-one acetate, 317 Preparation of 3/3-hydroxypregna-5,7-dien-20-one, 333... 

Ring-C ketones do not interfere with bromination at C-21. However, if a 3-ketone is also present during the reaction, the A-ring can be brominated simultaneously. This can be followed by dehydrobromination of the A-ring without removal of the 21-bromide. Thus, bromination of a 5a- or 5j -pregnane-17a-ol-3,20-dione gives a 2,4,21-tribromo compound which can be dehydrobrominated to a 21-bromo-17a-hydroxypregna-l,4-dien-3-one.173,199... 

Finally the chemical aromatization of Ring A which occurs in nature in the biosynthesis of estrogens must be mentioned. It can be done by thermal cleavage of the C-19 methyl group in l,4-dien-3-ones (H.H. Inhoffen, 1940 C. Djerassi, 1950) and was later achieved at lower temperatures with lithium — biphenyl in THF (H.L. Dryden, Jr., 1964). 

Experiment 6.135 A BENZYLIDENEACETONE (4-Phenylbut-3-en-2-one) B DIBENZYLIDENEACETONE (7,5-Diphenylpenta-l,4-dien-3-one)... 

Dehydrogenation of 3-kelo steroids. The dehydrogenation of 3-keto steroids to l,4-diene-3-ones with benzeneseleninic anhydride (8, 31) can be carried out in comparable yield by use of a process in which the benzeneseleninic anhydride is used in catalytic amounts and is continuously regenerated from diphenyl diselenide by oxidation with iodylbenzene. In practice, m-iodylbenzoic acid is a more convenient reagent, since m-iodobenzoic acid is easily recovered. 12-Keto and 12-hydroxy steroids arc oxidized by the catalytic system to A9(1 - -keto steroids in high yield. In fact, methyl desoxycholate (1) can be oxidized in this way directly to the trienedione 2 in 64% yield.1... 

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