Dimethyl maleate reduction

However, use of a less reactive reagent where [R = R =(CH2)4, (CH2)s, (CH2)20(CH2)2] led to the isolation of products 61 and 62, with a reduction in the yields of the desired cycloadducts. The product 62 arises from Michael addition of the liberated methanethiol to A-methylmaleimide. The protocol was further extended to olefinic dipolarophiles with dimethyl fiimurate, dimethyl maleate, fumaronitrile, and 2-chloroacrylonitrile leading to the corresponding adducts, although these dipolarophiles proved somewhat less reactive with reduced yields being observed. Where applicable, the alkene configuration was reflected in the relative stereochemistry of the cycloadducts (Fig. 3.5). 

In the reduction of dimethyl maleate, isomerization to fumarate was much faster than hydrogenation.171 In addition to a mechanism broadly similar to that for butadiene, a further pathway was thought to operate which involved an ordio-metallation of one PPh3 ligand, as shown in equations... 

Compound 87 (R = r-Bu, R = Ph, R = H) has been prepared by addition of tert-butylmagnesium chloride to 1-phenylphthalide (102) and subsequent dehydration with p-toluenesulfonic acid. It is described as a yellow oil with brilliant fluorescence under UV light, which on oxidation with sodium dichromate yields diketone 103. Compound 87 (R = /-Bu, R = Ph, R = H) with dimethyl acetylenedicarboxylategives 104(mp 128-129 C, 80%) on reduction 105 is obtained 105 is also accessible from 87 (R = <-Bu, R = Ph, R = H) and dimethyl maleate (mp 151-152°C, endo) a maleic anhydride adduct has also been described (mp 147.5-148°C, 83%). Diels-Alder adducts have been also prepared from the benzo[c]furan precursors 106 (R = CHjPh, R = H, Ph) in the presence of catalytic amounts of acid 107 (mp 141-142.5X, 70%) and 108 (mp 140-141.5°C, 49%) were obtained, which on catalytic hydrogenation (Pd/C) gave the exo isomers 109(110-1 irC) and 110(90-92°C, 125.5-127°C, dimorphism). The basis for these stereochemical assignments remains unclear, however. Compounds... 

For these reactions, an interesting mechanism involving a [2 -r 3] cydoaddition reaction is proposed (Scheme 11.5) [89]. The key reaction may be the [2 -r 3] reaction of 14 with alkene to give 16 via 15. The CO insertion reaction, followed by the reductive elimination of the formed 17, gives the product. The [2 -r 3] cydoaddition reaction has been found in the reaction of Ru(CO)3(l,4-diazabutadiene) with dimethyl maleate [91]. 

Figure 49. (a) In situ FTIR difference spectra for the reduction of 5% (w/v) dimethyl maleate in... 

The one-electron reduction of [Fe(CO)4(f/2-alkene)] (alkene = dimethyl-maleate, cinnamaldehyde, etc.) was initially thought (89) to afford the radical anions [Fe(CO)4(f/2-alkene)], but it is now clear (236) that the paramagnetic products are [Fe(CO)3(fj2-alkene)] the ESR spectra are consistent with a single electron localized largely on the metal atom but also weakly interacting with the ligand protons. The radical anions are substitutionally labile, with P(OMe) readily giving fluxional [Fe(CO)2- P(OMe)3 (>/2-alkene)] " (236). 

Carbonylation. Terminal alkynes give a mixture of 2-substituted dimethyl maleates and butenolides. Both oxidative and reductive pathways are followed. 

The resulting nucleophilic alkoxymethyl radical may be trapped by an electron-deficient alkene. Reduction of the adduct radical (3 by DCA radical anion and protonation of the resulting anion, confirmed by deuterium incorporation from methanol-OD, gives the final product (3%). The diastereoselectivity shown has its origin in a preference for protonation, under kinetic control, from the less hindered side. For acyclic alkenes such as methyl 2-cyanocrotonate or dimethyl maleate, free rotation within (395) results in a low cisJrans ratio of 1.8-2.5 1 whereas for cyclic alkenes such as N,3-dimethylmaleimide or 3-methylmaleimide the cisitrans ratio is considerably higher at 86 14. ... 

In the reduction of dimethyl maleate, isomerization to fumarate was much faster than hydrogena-... 

A versatile divergent route to the four diastereomeric dilactones (95)-(98) involves stereoselective reduction of the p-keto-ester (92) prepared by conjugate addition to dimethyl maleate (scheme 31) [87]. Stereoselective reduction followed by cyclisation to the anhydrides (93) and (94) sets up the configuration at one of the benzylic chiral centres. The second benzylic centre is defined in the reaction with an aromatic aldehyde leading ultimately to any one of the four possible stereoisomeric dilactones. 

Indirect electrochemical oxidative carbonylation with a palladium catalyst converts alkynes, carbon monoxide and methanol to substituted dimethyl maleate esters (81). Indirect electrochemical oxidation of dienes can be accomplished with the palladium-hydroquinone system (82). Olefins, ketones and alkylaromatics have been oxidized electrochemically using a Ru(IV) oxidant (83, 84). Indirect electrooxidation of alkylbenzenes can be carried out with cobalt, iron, cerium or manganese ions as the mediator (85). Metalloporphyrins and metal salen complexes have been used as mediators for the oxidation of alkanes and alkenes by oxygen (86-90). Reduction of oxygen and the metalloporphyrin generates an oxoporphyrin that converts an alkene into an epoxide. 

Comparing product ratios and limiting current densities from voltammetric data, the authors used their previously reported method for estimation of mass-transport coefficients to conclude that ultrasound was acting simply by agitation and not by cavitation. They further pursue the thesis that simple enhancement of mass transport will produce the same product switch in a more recent paper, but also describe work in which an increase in bulk reaction temperature from 0 to 60 produces a similar shift in products. xhe authors also noted less striking but still significant switches towards the 1-e products in other sonoelectrochemical reductions,67 e.g., dimethyl maleate at a lead cathode in an aqueous mixed-phosphate buffer, and benzyl bromide at a lead cathode in methanolic TEAR solution (Fig. 16). 

The preparation and a Diels-Alder reaction of (lE)-l,3-dimethoxybutadiene have been described. Dimethyl maleate and dimethyl fumarate each react with the hydrazone (92) to give the adduct (93) reductive cleavage of the N-N bond then gives the tetrahydropyridine (94) (Scheme 50). ... 

Gross redox-neutral processes catalyzed by EREDs isomerization of a-methylene-y-butyrolactone 67 to the thermodynamicaiiy favored oiefin 68 (top) [109] NADPH-free reduction of a dimethyl maleate 56 by concomitant oxidation and aromatization of a sacrificial substrate (bottom) [110]. 

A low-cost route to 1,4-butanediol and tetrahydrofuran based on maleic anhydride has been disclosed (Davy process).343,344 Here dimethyl or diethyl maleate is hydrogenated over a copper catalyst. Rapid saturation of the C—C double bond forms diethyl succinate, which subsequently undergoes further slower transformations (ester hydrogenolysis and reduction as well as dehydration) to yield a mixture of y-butyrolactone, 1,4-butanediol, tetrahydrofuran, and ethanol. After separation both ethanol and y-butyrolactone are recycled. 

One of the few mechanistic studies of mixed coupling reactions involves the reduction of dimethyl fumarate, or diethyl maleate, in the presence of the less easily reduced compounds 7 or cinnamon trile, [151]. In anhydrous DMF (BU4NI), the individual rate constants for dimerization of 52b and of 9 are known (110 and 880 M s respectively, (Tables 11 and 3) that is, 9 dimerizes faster than 52b by a factor of 8, and A 1/, = 0.41 V. With a twofold excess of 9 RRDE experiments at potentials where only 52b is reduced indicated that the normal RR homocoupling of 52b took place with a second-order rate constant identical to that measured in the absence of 9. RRDE experiments at a potential where both substrates are reduced revealed that electron transfer from 9 to unreduced 52b was the major reaction of [151]. No product studies were reported for... 

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