Dimethyl maleate, with cyclopentadiene

Earle and coworkers [54] have performed Diels-Alder reactions in neutral ionic liquids. The results of reactions of cyclopentadiene with dimethyl maleate, ethyl acrylate and acrylonitrile are reported in Table 6.10. The cycloadditions proceeded at room temperature in all of the ionic liquids tested, except [BMIMJPF4, and gave almost quantitative yields after 18-24h. The endo/exo selectivity depends on dienophile. No enantioselectivity was observed in the [BMIM] lactate reaction. 

Table 6.10 Diels-Alder reactions of cyclopentadiene with dimethyl maleate, ethylacrylate and acrylonitrile in neutral ionic liquids...

In the Diels-Alder reaction of cyclopentadiene with dimethyl maleate, both exo and endo products are theoretically possible. Only the endo product 6-6 is found. 

The stereochemistry of the adduct obtained in many Diels-Alder reactions can be selected on the basis of two empirical rules formulated by Alder and Stein in 1937. According to the cis principle , the relative stereochentistry of substituents in both the dienophile and the diene is retained in the adduct. That is, a dienophile with trans substituents will give an adduct in which the trans configuration of the substituents is retained, while a cis disubstituted dienophile will form an adduct in which the substituents are cis to each other. This aspect is often referred to as the stereospecific nature of the Diels-Alder reaction. For example, in the reaction of cyclopentadiene with dimethyl maleate, the cis adducts 74 and 75 are formed, while in the reaction with dimethyl fumarate, the trans configuration of the ester groups is retained in the adduct 76 (3.64). 

Diels-Alder transition states for the reaction of 1,3-cyclopentadiene with dimethyl maleate. 

Similarly, cyclopentadiene reacted with dimethyl maleate or methyl methacrytate in aqueous medium (Schemes 4 and 5). 

Diels-Alder reactions are stereospecific with respect to the E- and Z-relationships in both the dienophile and the diene. For example, addition of dimethyl fumarate and dimethyl maleate with cyclopentadiene is completely stereospecific with respect to the cis or trans orientation of the ester substituents. 

Another example of the retention of volatile DA reagents is that of cyclopentadiene in a tandem retro-DA/DA prime reaction [15, 16, 38], This reaction type is the thermal decomposition of a DA adduct (A) and the generation of a diene (generally the initial diene) which is trapped in situ by a dienophile leading to a new adduct (B) [39]. Cyclopentadiene (22) (b.p. 42 °C) is generated by thermolysis of its dimer at approximately 160 °C [40]. An equimolar mixture of commercial crude dicyclopenta-diene (21) and dimethyl maleate was irradiated in accordance with the GS/MW process, in an open reactor, under 60 W incident power, for 4 min (8 x 30 s). The expected adduct 23 was isolated in 40% yield (Scheme 7.1). The isomeric composition of 23 (endo-endoIexo-exo = 65/35) was identical with that obtained under classical conditions from 22 and methyl maleate [41]. The overall yield of this tandem reaction can be increased from pure dimer 21 (61%) and the same tandem reaction has also been reported using ethyl maleate as dienophile [31]. 

Complete stereoselectivity occurs in the Diels-Alder reaction through syn addition of the dienophile to the diene. Hence, the reaction of dimethyl fumarate and dimethyl maleate with cyclopentadiene yields the trans and cis adducts, respectively (Scheme 26.1).29... 

The first report of the use of racemic sulfinyl maleates as dienophiles appeared in 1983 [85]. This paper described the synthesis of 2-phenylsulfmyl maleate and fumarate, but only the reaction of cyclopentadiene with the first ( )-87, a synthetic equivalent of dimethyl acetylenedicarboxylate, was studied. The reaction takes place at room temperature on silica gel and the stereochemistry of the adducts remained undetermined because the isolated product is the compound resulting from the pyrolytic sulfinyl elimination, which occurs spontaneously under the reaction conditions used (Scheme 46). 

Similarly, a mixture of endo- and exo-adducts is formed during the reaction of dimethyl maleates with cyclopentadiene As pointed out... 

It has been shown so far that the endo product is formed in a kinetically controlled step. It is the favored product at lower temperatures. Furthermore, the endojexo ratio may be affected by the polarity of the solvent. By studying the reaction of cyclopentadiene and acrylates, Berson has shown that solvents of high polarity favor the endo product. This is so, it is argued, because the latter goes through a transition state which is more polar than that for the exo product. Certain Lewis acids which catalyze the DA reaction are also shown to affect the endojexo ratio of the product from diethyl maleate and dimethyl maleate with cyclopentadiene (see Table 4.8). 

In 1988 Koizumi et al. reported the first sulfoxide used as a chiral synthetic equivalent of dimethyl acetylene dicarboxylate [86a]. The synthesis of dimethyl (R)s-2-(10-isobornylsulfmyl) maleate (88), its reaction with cyclopentadiene catalyzed by ZnCl2, and the further transformation of the major adduct 89 into a half-ester 90 (which had been used as the starting material for the synthesis of carbocyclic nucleosides (-)-aristeromycin and (-)-neplanomicin) are described (Scheme 46). 

Koizumi and coworkers have developed a new enantiomerically pure a,p-unsaturated sulfoxide dienophile bearing the isoborneol group as a chiral auxiliary, dimethyl (f )-2-(10-isoborneolsulfinyl)maleate (214), which has been successfully employed as a chiral synthetic equivalent of dimethyl acetylenedicarboxylate [174], The dienophile (214) underwent cycloaddition with cyclopentadiene, in the presence of zinc chloride, with high stereo- and diastereoselectivity (92% single endo diastereoisomer, 6% single exo diastereoisomer) to yield the major cycloadduct (215), which was subsequently transformed into the half-ester (216), an intermediate in the syntheses of (-)-aristeromycin (199) and (-)-neplanocin A (200). Cycloadduct (215) has also recently been used for the synthesis of bicyclo[2.2.1]heptane lactone (217) [175,177], which itself is an intermediate in the synthesis of the iridoid (-)-boschnialactone [176] (218) (Scheme 5.69), and also in the formal synthesis of (-)-aristeromycin (199) and (-)-neplanocin (200) [177]. 

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