Dialkyl fumarate

Addition of dialkyl fumarates to DAP accelerates polymerization maximum rates are obtained for 1 1 molar feeds (41). Methyl aUyl fumarate [74856-71-6] (MAF), CgH QO, homopolymerizes much faster than methyl aUyl maleate [51304-28-0] (MAM) and gelation occurs at low conversion more cyclization occurs with MAM. The greater reactivity of the fumarate double bond is shown in copolymerization of MAF with styrene in bulk. The maximum rate of copolymerization occurs from monomer ratios, almost 1 1 molar, but no maximum is observed from MAM and styrene. Styrene hinders cyclization of both MAF and MAM. 

A reactive surfactant shown next (RS) was used as a comonomer in a seeded polymerization. RS was easily adsorbed on seed particles due to their amphiphilicity. If dialkyl fumarate was preabsorbed in the particle, the polymerization proceeded quickly and resulted in the formation of skin layer of RS-fumarate copolymer. Because the vinyl group in RS is an allyl type, RS in aqueous phase hardly polymerizes and no water-soluble homopolymer was formed. The active ester group of RS on the skin layer was used for the preparation of functional microspheres (18). 

The use of prochiral alkenes such as propene, 2-butene, tran -dideutereoethylene, dialkyl fumarates, and trani-dimethoxyethylenes, have allowed detailed structural and mechanistic studies of alkene complexes. The diastereomers produced upon binding of prochiral alkenes to CpM(CO)X centers provided the key complexes to prove that interconversions occurred by rotations about the metal-(C=C) axis. Thus observations that neither the chirality at the metal nor at the alkene is changed in the rearrangement of a trans-substituted alkene provided proof that the nature of the dynamic process was a propeller rotation. Note that in equation (9) the equilibrium between (20) and (21) averages enviromnents b and d separately from a and c. A key feature is that olefin rotation does not alter the chirahty at the olefin because of the olefin-metal bond. 

When electron deficient alkenes are added to cyclopropene derivatives (74 equation 33) and (77 equation 34) in the presence of [Ni(COD)2], vinylcyclopropanes are formed in good yields. For example, dialkyl fumarate or maleate reacts with 3,3-dimethylcyclopropene in the presence of [Ni(COD)2] to give 2,3-bis(alkoxycarbonyl)-l-(2-methyl-l-propenyl)cyclopropanes (75), (76), (78) and (79), in which alkene stereochemistry is chiefly retained, in 50-73% yields. Reaction of methyl acrylate with 3,3-dimethylcyclopropene results in the formation of several products, while reaction of methyl acrylate with 3,3-diphenylcyclopropene gives vinylcyclopropane derivatives (80 equation 35) in 85% yield. Under similar conditions, methyl crotonate reacts with (74a) to give (82) in low yield (equation 36). Catalysis with nickel(0)/PR3, 2 [Ni(CO)4], 3 [Pd(DBA)2] or [Pd(DBA)2]/PlV33 gives mainly... 

Kinetic studies of the reaction of CO2 with radical anions generated from dialkyl fumarates and maleates showed that C-C bond formation was the rate-determining step. The pseudo first-order rate constants, kco2, for fumarate radical anions in C02-saturated DMF were found to vary between 0.35 and 1.5 s and to decrease in the same order as observed for dimerization [218]. Rate constants for maleates (kco2 varied from 32.0 s to 18.0 s ) were higher. Rather slow is the coupling of CO2 with the 4-keto isophorone in MeCN (k co2 = 0-35 s ) [219]. 

The dimerization rate constants of dialkyl fumarates [k — 25-120 m s ) [236] decrease with increasing steric hindrance of the alkyl group and prove to be significantly smaller than those of fumaronitrile [k = l x 10 m s ) [240], The elec-trochemically generated dimethyl maleate undergoes rapid cis trans isomerization to the dimethyl fumarate then rapid radical anion dimerization [241], In comparison, the EHD rate constant for 4-methylcoumarin (A = 1.8 x 10 M s ) proved similar to that of a relatively fast cinnamate (4-cyano k — 5.7 x 10 M s ) [242]. 

Alkenes activated by electron-withdrawing groups at both ends of the double bond are more easily reduced than the analogous singly substituted alkenes, and the radical anions formed are less reactive. Examples include fumarodinitrile compared to acrylonitrile and dialkyl fumarates compared to alkyl acrylates. Fumarodinitrile (51) [2,35,36,48,55,70,71, 124] and simple alkyl fumarates (52) [7,10,15,55,70,125,126] have therefore been the subjects of a number of mechanistic studies as models for acrylonitrile and alkyl acrylates. Examples of the formation of LHDs on a preparative scale are given later, in Table 12. 

The thermally more stable alkyl- or arylsubstituted cyclopropenes can undergo this reaction type with the aid of transition metal catalysts under mild conditions. The choice of a suitable catalyst strongly depends on the nature of the olefinic cosubstrate. For electron-deficient alkenes, Ni(cod)2 (where cod = cis-cycloocta-1,5-diene) has been found to be the best catalyst66). Dialkyl maleates, dialkyl fumarates and methyl... 

Ni(cod)2 or mixtures of Ni(cod)2 with an electron deficient alkenes (e.g. dialkyl fumarate or maleic anhydride) have been found to be the most efficient catalysts for the cyclodimerization of methylenecyclopropane and 2-methylmethylenecyclopropane no. i7i) Ni(cod)2 the combined yields of cyclodimerization products afe lower, but the ratio or four-membered to five-membered rings is higher. The reverse holds for the modified catalysts (Eq. 66). 

These reactions proceed smoothly at 20 to 40 °C with high regio- and stereoselectivity. When alkyl acrylates with an optically active alkyl group are applied, 3-methyl-enecyclopentyl carboxylates are obtained with up to 64 % d.e.188). Interestingly, dialkyl fumarates and maleic anhydride do not react as cosubstrates but function as controlling ligands resulting in a considerable enhancement of the cyclodimerization of methylenecyclopropane (see p. 106). 

Most interestingly, dialkyl maleates no longer give rise to Type B cycloadducts but end up exclusively as Type A cycloadducts 189) (cf. Scheme 5). The same has been found with electron deficient cosubstrates such as dialkyl fumarates or 2,3-di(methoxycarbonyl)norbomene189) (Eq. 82). 

Remarkably, with 3,3-dimethoxycyclopropene, the stereochemical outcome of the [2 4-1] cycloaddition reaction with dialkyl fumarate and maleate is different to that observed for the other 3,3-disubstituted cyclopropenes (Table 3). With the 3,3-dimethoxy derivative only the thermodynamically more stable 1,2-tra s-dialkoxycarbonylcyclopropanes are formed. This can be taken as an indication for a stepwise addition process with an intermediate of highly zwit-terionic character (structure 29 B or 29 C) that can undergo rotational isomerization to form the thermodynamically most stable product, i.e. the tranx-configurated diester. 

For the dimerization of 2-methyl-, 2,2-dimethyl- and 2,2,3,3-tetramethylmethylenecyclo-propane the bis(cycloocta-l,5-diene)nickel(0) catalyst was modified with dialkyl fumarate, maleic anhydride, or various trialkylphosphanes. For all of the substituted methylenecy-clopropanes but the tetramethyl derivative, dimers of the spiro[2.4]heptane and dispiro[2.1.2.11-octane type were obtained in good yields. 

Interestingly, dimerization also occurs selectively in the presence of other electron-deficient alkenes as solvents, such as dialkyl fumarates. The formation of trimers and polymers is markedly reduced in these cases. 

With /1-substituted unsaturated esters, e.g. methyl ( )-crotonate or dimethyl maleate, the stereochemistry at the alkene group is predominantly retained in the products, i.e. methyl rra7i -2-mcthyl-3-methylenecyclopentanecarboxylate (3) and dimethyl 3-methylenecyclopen-tane-1,2-dicarboxylate (4), when phosphane-free nickel catalysts are employed at temperatures slightly above room temperature. When equimolar amounts of MCP and dimethyl maleate are used, approximately equal amounts of homocyclodimers of MCP and [3 + 2] cycloadducts arc obtained, even if the MCP is added dropwise to the catalyst solution in dimethyl maleate, indicating that the cycloaddition is a relatively slow reaction. When the maleate/MCP substrate ratio is increased to 3 1, the yield of the codimers 4 is raised to 78%.Dialkyl fumarates and maleic anhydride do not undergo cycloaddition under these conditions. 

Compared with the naked nickel reactions, reactions with phosphane-modified nickel catalysts require higher temperatures (80-100 C) in order to proceed at a reasonable rate and usually exhibit a decreased stereoselectivity. Despite these obvious drawbacks, such catalyst systems are advantageous in the case of highly electron-deficient alkenes, such as ( )-but-2-enal. ° or dialkyl fumarates, which can be readily employed as cycloaddition substrates only with modified nickel catalysts (vide supra). 

Whereas palladium(0)-catalyzed reactions of dialkyl fumarate and dialkyl maleate yield reaction products identical to those obtained from the phosphane-modified nickel-catalyzed reactions (vide supra), analogous palladium(0)-catalyzed reactions with ( )-but-2-enoic or (E)-cinnamic acid derivatives lead to different products to the nickel-catalyzed reactions, i.e. in the palladium-catalyzed reactions formal distal cleavage of but-2-enoic MCP occurs to provide methyl tra i-2-methyl-4-methylenecyclopentanecarboxylate (12, R = Me) and methyl trans-4-methylene-2-phenylcyclopentanecarboxylate (12, R = Ph), respectively." Yields and stereoselectivities are slightly higher with palladium(O) catalysts. When R = Me, 7.4% of the C-C double bond isomerization product, methyl traM -2,4-dimethylcyclopent-3-enecarboxylate (13, R = Me), is additionally obtained, raising the combined yield of cyclocodimers to 49.9%. With methyl (jE )-cinnamate, analogous isomerization only occurs upon workup, i.e. distillation of the crude product. 

Several examples of polyamides made with this process are given in Tables 5.1 and 5.2 [44, 45]. The enzymatic process is milder in temperature and produces narrower molecular weight distributions relative to the chemical process. An additional advantage is that some polyamides that are not easily synthesized via the chemical process, can be made via the enzymatic process, for example, the polyamides derived from dialkyl malonate, dialkyl fumarate, and dialkyl maleate. 

More dramatically, perhaps, is the observation that the reaction with dialkyl maleates occurs via distal C — C bond cleavage to form exclusively type A adducts. The same is true for dialkyl fumarates and 2,3-(dimethoxycarbonyl)norbornenc49. 

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