Alkenes, cyclic => diketones

Cyclic diketones can be the predecessors of quinoxaline macrocycles, obtained in one stage with the oxidation of cyclic alkenes with potassium permanganate (1971JA3303) or in two stages by the cyclotrimerization of cyclic alkynes and subsequent ozonolysis of compounds 18 (1986JOC3257). Along with the formation of diketone 4 the latter reaaion leads, to the unstable hexaketone 19. The reaction of the mixture of compounds 4 and 19 with the DAB leads to macrocycles 20 and 21 with one or three quinoxaline fr pients, respectively, with 10% and 3% yields, calculated in two st es.The synthesis of the macrocycle 20a from the analytically pure diketone 4a was in quantitative yield. 

Cyclic diketones can be the predecessors of quinoxaline macrocycles, obtained in one stage with the oxidation of cyclic alkenes with potassium permanganate... 

The bis(trimethylsiloxy)alkene bromination procedure is a large-scale preparation that gives excellent yields of cyclic and acyclic 1,2-diones however, when enolizable 1,2-diketones are produced, some complications can be encountered.7,8... 

Gleiter has studied the reaction of diynes with alkenes as an intermediate step in the synthesis of ansa-metallocenes 164. They have reacted acyclic diynes with ethylene [161] and cyclic diynes 162 in supercritical ethylene [162] giving tricyclic diketones 163 in low to moderate yields. The presence of coordinating heteroatoms in the link increased the reaction yields (Scheme 48) [163]. 

Chloro(methoxy)- and chloro(phenoxy)carbenes, which are generated from the diazirine precursors, behave as ambiphiles in additions to alkenes, exhibiting high reactivities toward both electron-poor and electron-rich olefins. Methoxy(phenyl)- and ferrocenyl(methoxy)methylenes have been transferred in a stereospecific manner from transition metal complexes of these species to electron-deficient alkenes. Irradiation of benzocyclobutanedione with UV light induces a rearrangement of the cyclic a-diketone to 17, which has been trapped by alkenes in good yields " . Thermolysis of 18 gives rise to nucleophilic dimethoxycarbene, which has been intercepted by electron-deficient olefins or by styrene derivatives. 

Carboxylic acids can be converted by ancxlic decarboxylation into radicals and/or carbocations. The reaction conditions are simple an undivided beaker-type cell as reaction vessel, controlled current supplied from an inexpensive d.c. power supply and meAanol as solvent are in most cases sufficient. A scale-up is fairly easy and the yields are in general good. By the radical pathway 1,/i-diesters, -diketones, -dienes and -dihalides, chiral intermediates for synthesis, pheromones and unusual fatty acids are accessible in just a few steps. The addition of the intermediate radicals to double bonds affords additive dimers, whereby four building units, two alkyl radicals from the carboxylates and two alkenes, can be coupled in one step. Five-membered hetero- or carbo-cyclic compounds can be prepared by intramolecular addition starting from unsaturated carboxylic acids. 

Following upon their previous experiences with oxidative coupling chemistry with THBP, Li and co-workers recently reported an oxidative allylic alkylation reaction between activated methylene nucleophiles 46 (such as diketones and ketoesters) with cyclic alkenes 47 catalyzed by CuBr and C0CI2 (Scheme 27) [50]. 

Intermolecular de Mayo reactions are efficient for cyclic 1,3-diketones such as dimedone (5,5-dimethyl-l,3-cyclohexanedione)96,103,104 and acyclic systems such as acetylacetone93-95. Unsymmetrical acyclic /l-diketones, such as 1-phenyl-1,3-butanedione98 can enolize in two directions, however, reaction normally occurs preferentially from a single enol form. Examples of alkene photocycloaddition to trapped ends of /(-dicarbonyl compounds (e.g., 2,2-dimethyl-3(2/f)-furanone and 2,2.6-trimethyl-4/f-l,3-dioxin-4-one) are given in Table 1 (entries 26, 27) and Table 2 (entry 35) 10°. If the enol is stabilized by derivatization (e.g., acetylated dimedone 3-acetoxy-5,5-dimethyl-2-cyclohexenone), the primary cyclobutane photoproducts can be isolated96. 

More complex products are obtained from cyclizations in which the oxidizable functionality and the alkene are present in the same molecule. y9-Keto esters have been used extensively for Mn(III)-based oxidative cyclizations and react with Mn(OAc)3 at room temperature or slightly above [4, 10, 11, 15], They may be cyclic or acyclic and may be a-unsubstituted or may contain an a-alkyl or chloro substituent. Cycloalkanones are formed if the unsaturated chain is attached to the ketone. y-Lactones are formed from allylic acetoacetates [10, 11]. Less acidic /3-keto amides have recently been used for the formation of lactams or cycloalkanones [37]. Malonic esters have also been widely used and form radicals at 60-80 °C. Cycloalkanes are formed if an unsaturated chain is attached to the a-position. y-Lactones are formed from allylic malonates [10, 11]. yff-Diketones have been used with some success for cyclizations to both alkenes and aromatic rings [10, 11]. Other acidic carbonyl compounds such as fi-keto acids, /3-keto sulfoxides, j8-keto sulfones, and P-nitro ketones have seen limited use [10, 11]. We have recently found that oxidative cyclizations of unsaturated ketones can be carried out in high yield in acetic acid at 80 °C if the ketone selectively enolizes to one side and the product cannot enolize... 

Schemes Reaction of alkenes with cyclic 1,3-diketones...

Further extension of this strategy to the asymmetric functionalization of cyclic a,(3-unsaturated ketones was later reported by the same group [107], 9- z-amino cinchona alkaloid salt 57 proved to be the optimal catalyst to afford the key intermediates 104, which are useful precursors for a series of important building blocks including alkynes, alkenes, 1,3-diketone, and bicyclic compounds (Scheme 5.50). 

For any alkene, hydrogen peroxide may be used as the oxidizing agent and either dimethyl sulfide or zinc and acetic acid may be used as the reducing agent (see Chapter 18, Section 18.4.3). Ozonolysis of a cyclic alkene leads to oxidative cleavage to a diketone, a dialdehyde, a keto-aldehyde, a keto acid, or a dicarboxylic acid. When 1,3-dimethylcyclopentene (67) is treated with ozone and then with zinc and acetic acid, oxidative cleavage leads to keto-aldehyde 68 (2-ethyl-5-oxooctanal). 

The photochemical reactivity of P-ketoesters is different form that of P-diketones. Irradiation of a P-ketoester in the presence of an alkene produces oxetane via the ketone carbonyl instead of the desired cyclobutane ring system. Therefore, it is necessary to covalently lock the ketoesters as the enol tautomers. To this end, silyl enol ethers, 129 and 132a, and enol acetates, 130 and 132b, were prepared, but these substrates still fail to undergo the desired intramolecular [2 + 2] photocycloaddition with olefins. The only new products observed in these reactions result from the photo-Fries rearrangement of the cyclic enol acetate (130 to 131) and cis-trans isomerization of both acyclic substrates 132a/b. However, tetronates are appropriate substrates for both intermolecular and intramolecular photocycloadditions with olefins. In addition, enol acetates and silyl enol ethers of p-keto esters are known to undergo [2 + 2] photoaddition with cyclic enones (vide infra). 

Photoinduced reactions of cyclic a-diketones with different alkenes takes place via [2 + 2], [4 + 2] or [4 + 4] photocycloaddition pathways. Photoaddition of electron deficient silyl ketene acetals to 2-, 3- and 4-acetylpyridine generates oxetanes as major products. The reaction is favoured in non polar solvents. The photoreaction between silyl enol ethers and henzil affords [2 + 2] cycloaddition products, while in the case of 9,10-phenanthrenequinone [4 + 2] cycloacidition predominates. Photocycloaddition of p-henzoquinones to hicyclopropylidene affords spirooxetanes (21) as the primacy products further irradiation leads to rearranged spiro[4.5]deca-6,9-diene-2,8-diones. With 9,10-anthraqui-none, in addition to the spirooxetane, a spiro[indan-l,l -phthalan]-3 -one is also obtained. ... 

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