1.3- Dicarbonyl compounds from alkenes

Carbon radicals generated by the addition of enol radicals derived from 1,3-dicarbonyl compounds to alkenes are efficiently trapped by oxygen in a chain reaction leading to hemiperacetals [51], The process is illustrated by the electrochemical or AIBN-initiated reaction of 2-methyl-1,3-cyclopentanedione with styrene and oxygen in acetonitrile, which provides the thermodynamically favored all-c bicyclic peroxide in good yield (Scheme 23) [51],... 

The [2 + 2] cycloaddition of enol acetates of 1,3-dicarbonyl compounds to alkenes yields masked aldols, which can be modified in a number of ways. Treatment of the adduct (19), derived from ethylene and 3-acetoxycyclohex-2-enone, with base gave the a,/3-unsaturated ketone (20) which yielded the propellane (21) upon irradiation in the presence of ethylene. Ring contraction led ultimately to the highly strained [2,2,2]propellane (22) (Scheme 5). ... 

The obvious Vfittig disconnection gives stabilised ylid (5fi) and keto-aldehyde (57). We have used many such long-chain dicarbonyl compounds in this Chapter and they are mostly produced from available alkenes by oxidative cleavage (e.g. ozonolysis). In this case, cyclic alkene (58) is the right starting material, and this can be made from alcohol (59) by elimination,... 

The reaction, formally speaking a [3 + 2] cycloaddition between the aldehyde and a ketocarbene, resembles the dihydrofuran formation from 57 a or similar a-diazoketones and alkenes (see Sect. 2.3.1). For that reaction type, 2-diazo-l,3-dicarbonyl compounds and ethyl diazopyruvate 56 were found to be suited equally well. This similarity pertains also to the reactivity towards carbonyl functions 1,3-dioxole-4-carboxylates are also obtained by copper chelate catalyzed decomposition of 56 in the presence of aliphatic and aromatic aldehydes as well as enolizable ketones 276). No such products were reported for the catalyzed decomposition of ethyl diazoacetate in the presence of the same ketones 271,272). The reasons for the different reactivity of ethoxycarbonylcarbene and a-ketocarbenes (or the respective metal carbenes) have only been speculated upon so far 276). 

Examples of the Michael-type addition of carbanions, derived from activated methylene compounds, with electron-deficient alkenes under phase-transfer catalytic conditions have been reported [e.g. 1-17] (Table 6.16). Although the basic conditions are normally provided by sodium hydroxide or potassium carbonate, fluoride and cyanide salts have also been used [e.g. 1, 12-14]. Soliddiquid two-phase systems, with or without added organic solvent [e.g. 15-18] and polymer-supported catalysts [11] have been employed, as well as normal liquiddiquid conditions. The micellar ammonium catalysts have also been used, e.g. for the condensation of p-dicarbonyl compounds with but-3-en-2-one [19], and they are reported to be superior to tetra-n-butylammonium bromide at low base concentrations. 

The Michael reaction is the conjugate addition of a soft enolate, commonly derived from a P-dicarbonyl compound 24, to an acceptor-activated alkene such as enone 41a, resulting in a 1,5-dioxo constituted product 42 (Scheme 8.14) [52]. Traditionally, these reactions are catalyzed by Bronsted bases such as tertiary amines and alkali metal alkoxides and hydroxides. However, the strongly basic conditions are often a limiting factor since they can cause undesirable side- and subsequent reactions, such as aldol cyclizations and retro-Claisen-type decompositions. To address this issue, acid- [53] and metal-catalyzed [54] Michael reactions have been developed in order to carry out the reactions under milder conditions. 

A route to pyrroles illustrated by the preparation of 292 involves initial treatment of the nitroketene-5, 5 -acetal 293 with an organometallic reagent, followed by conversion of the resulting alkene 294 to the enamine 295, and final annulation to the target heterocycle (Scheme 34) <1998T12973>. A related approach featuring constmction of /3-hydroxyenamines from 1,3-dicarbonyl compounds and /3-amino alcohols, and subsequent palladium-catalyzed cyclization to pyrroles, has been reported <1996TL9203>. 

In 1977, McMurry and Kees [152] developed a titanium-induced intramolecular coupling procedure to form cycloalkenes from dicarbonyl compounds. Mechanistically, as shown in Scheme 85, the coupling reaction proceeds by an initial pinacol dimerization of the dicarbonyl 253 to 254, followed by titanium-induced deoxygenation to afford alkene 255. 

The applications of ruthenium tetroxide range from the common types of oxidations, such as those of alkenes, alcohols, and aldehydes to carboxylic acids [701, 774, 939, 940] of secondary alcohols to ketones [701, 940, 941] of aldehydes to acids (in poor yields) [940] of aromatic hydrocarbons to quinones [942, 943] or acids [701, 774, 941] and of sulfides to sulfoxides and sulfones [942], to specific ones like the oxidation of acetylenes to vicinal dicarbonyl compounds [9JS], of ethers to esters [940], of cyclic imines to lactams [944], and of lactams to imides [940]. 

Transition metal catalysis of the Michael reaction of 1,3-dicarbonyl compounds with acceptor activated alkenes has been known since the early 1980 s 2>3 It is a valuable alternative to the classic base catalysis of the reaction. Because of the mild and neutral conditions, the chemoselectivity of these reactions is superior to that provided by base catalysis, since the latter suffers from various unwanted side or subsequent reactions, such as aldol cyclizations, ester solvolyses or retro-Claisen type decompositions. A number of transition metal and lanthanide compounds have been reported to catalyze the Michael reaction, but FeCb 6 H20 is one of the most efficient systems to date. A number of 3-diketones or p-oxo esters and MVK are cleanly converted to the corresponding Michael reaction products within a few hours at room... 

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. 

Manganese(III) can oxidize carbonyl compounds and nitroalkanes to carboxy-methyl and nitromethyl radicals [186]. With Mn(III) as mediator, a tandem reaction consisting of an intermolecular radical addition followed by an intramolecular electrophilic aromatic substitution can be accomplished [186, 187). Further Mn(III)-mediated anodic additions of 1,3-dicarbonyl and l-keto-3-nitroalkyl compounds to alkenes and alkynes are reported in [110, 111, 188). Sorbic acid precursors have been obtained in larger scale and high current efficiency by a Mn(III)-mediated oxidation of acetic acid acetic anhydride in the presence of butadiene [189]. Also the nitromethylation of benzene can be performed in 78% yield with Mn(III) as electrocatalyst [190]. A N03 radical, generated by oxidation of a nitrate anion, can induce the 1,4-addition of aldehydes to activated olefins. NOj abstracts a hydrogen from the aldehyde to form an acyl radical, which undergoes addition to the olefin to afford a 1,4-diketone in 34-58% yield [191]. 

Cycloalkylation of p dicarbonyl compounds. The radicals generated from Mn(III) oxidation of j3-dicarbonyl compounds add to alkenes efficiently. Lactone formation from alkenes is improved by ultrasound (45-80% yield). ... 

Carbonyl couplings. Many variations of cross couplings are possible these include aldehydes with a-dicarbonyl compounds. Ketyl radicals derived from carbonyl compounds also add to alkenes such as acrylonitrile " or N-allyl moieties. Intramolecular cyclizations on terminal alkenes or allene species have also been exploited for synthetic purposes. 

Derivatives of d- and L-thrcitol with ether groups in positions 1 and 4, such as 33 and 34, have been used for the synthesis of chiral alkenes (Section D.l. 6.1.5.) and for the formation of monoke-tals with dicarbonyl compounds which then add Grignard reagents enantioselectively (Section D.l.3.1.4.). Both enantiomers of 1,4-di-O-benzylthreitol 33 and 1,4-di-O-methylthreitol 34 are commercially available and can be prepared from tartaric acid via the intermediate 4,5-bis(hy-droxymethyl)-2,2-dimethyl-1,3-dioxolanes (vide supra), either via butanediepoxide23,45 or directly by alkylation/hydrolysis23 46. 

Compounds with weak C—H bonds can add to alkenes by a free-radical chain mechanism. Compounds that can add to alkenes in this way include RCHO compounds (aldehydes, formates, etc.) and 1,3-dicarbonyl compounds. In the initiation part of the mechanism, an initiator radical abstracts H- from the weak C—H bond to give an alkyl radical. In the propagation part of the mechanism, the alkyl radical adds across the C=C rrbond, and then the new radical abstracts H- from the weak C—H bond to give the product and regenerate the first alkyl radical. 

Several 3-(2H)-pyridazinones have been prepared from monophenyl hydrazones of 1,2-dicarbonyl compounds and a variety of active methylene compounds within 1-20 min without solvent under focused irradiation conditions in the presence of carefully adjusted amounts of piperidine or solid potassium tert-butoxide (isolated yields 50-89%), in accordance with Scheme 10.109 [216]. In the synthesis of the pyridazinone 44, microwave irradiation has no specific effect, because the result (72%) was identical with that obtained by use of classical heating under the same conditions. With the dry media procedure it was possible to isolate the intermediate alkene, which was not obtained in the previously reported procedure. When the active methylene compound is a keto ester, the reaction follows a different pathway [216b]. 

The McMurry reaction (see Section 2.9) can allow the formation of alkenes from dicarbonyl compounds. This reaction generates an intermediate 1,2-diol (pinacol), which is converted on the surface of the titanium to the alkene. The two carbon-oxygen bonds do not break simultaneously and the reaction is not stereospecific. Thus, both anti and syn acycUc 1,2-diols give mixtures of Z- and -alkenes. With cyclic 1,2-diols, the two oxygen atoms must be able to bond to a common titanium surface. Thus, the cis-diol 45 eUnunates to the alkene 46, whereas the trans-dio 47 is inert under these reaction conditions (2.43). ... 

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