Methyl acrylate, Diels-Alder reaction with cyclopentadiene

The Diels-Alder reaction provides us with a tool to probe its local reaction environment in the form of its endo-exo product ratio. Actually, even a solvent polarity parameter has been based on endo-exo ratios of Diels-Alder reactions of methyl acrylate with cyclopentadiene (see also section 1.2.3). Analogously we have determined the endo-exo ratio of the reaction between 5.1c and 5.2 in surfactant solution and in a mimber of different organic and acpieous media. These ratios are obtained from the H-NMR of the product mixtures, as has been described in Chapter 2. The results are summarised in Table 5.3, and clearly point towards a water-like environment for the Diels-Alder reaction in the presence of micelles, which is in line with literature observations. 

The diastereoselection of the Diels Alder reaction of methyl acrylate with cyclopentadiene was investigated [74] in microemulsions prepared with isooctane oil, CTAB as surfactant and 1-butanol as cosurfactant, and the results were compared with those found in pure solvents and water (Table 6.12). In emulsions rich in 1-butanol and formamide (entries 1 and 4) the reaction was slow (72 h) and the diastereoselectivity was practically the same as that... 

Table 6.12 Diastereoselectivity of Diels-Alder reaction of methyl acrylate with cyclopentadiene in formamide microemulsion and pure solvents...

Chiral Lewis Acid. These chiral titanium reagents are widely used as chiral Lewis acid catalysts. The Diels-Alder reaction of methyl acrylate and cyclopentadiene affords the endo adduct in moderate enantioselectivity when a stoichiometric amount of the chiral titanium reagent (5) is employed (eq 6). Use of 3-(2-alkenoyl)-l,3-oxazolidin-2-ones as dienophiles greatly improves the optical purity of the cycloadduct when the 2-phenyl-2-methyl-1,3-dioxolane derivative (6) is used as a chiral ligand. Most importantly, the reaction proceeds with the same high enantioselectivity for the combination of various dienophiles and dienes even when 5-10 mol % of the chiral titanium reagent is employed in the presence of molecular sieves 4A (eqs 7 and 8). ... 

The ligand (S)-VAPOL 36 was developed by the Wullf group and was successfully applied in the aluminium-catalysed asymmetric Diels-Alder reaction of methyl acrylate and methacrolein with cyclopentadiene (Scheme 19.45). It was also found that carbonyl additives displayed positive cooperativity with the (S)-VAPOL 36-diethylealuminium chloride catalyst on the autoinduction for the reaction with methyl aciylate. 

Table 15. Mass loss and reaction conversion with recycled IL [C6inim][BF4] used in Diels-Alder reaction of methyl acrylate and cyclopentadiene [Ilgen, 2009]...

Good yields and high diastereoselectivities were obtained by using zeolites in combination with Lewis-acid catalyst [21]. Table 4.7 illustrates some examples of Diels-Alder reactions of cyclopentadiene, cyclohexadiene and furan with methyl acrylate. Na-Y and Ce-Y zeolites gave excellent results for the cycloadditions of carbocyclic dienes, and combining these zeolites with anhydrous ZnBr2 further enhanced the endo diastereoselectivity of the reaction. An exception is the cycloaddition of furan that occurred considerably faster and with better yield, in comparison with the classic procedure [22], when performed in the presence of sole zeolites. 

The Diels-Alder reaction has also been used to prepare special reagents. Thomas and coworkers80, for instance, studied the Diels-Alder reactions of methyl (E)- and (Z)-3-(triphenylstannyl)acrylates 72a and 72b with cyclopentadiene and converted the organostannanes obtained to tin hydrides. (E)-72a afforded endo 73 exclusively with 99% yield, whereas (Z)-72b afforded a 2 1 mixture of endo 74 and exo 75 with 77% overall yield (equation 24). Cycloadduct 73 was easily converted to tin hydride 76. By... 

The first report of an asymmetric Diels-Alder reaction with chiral Lewis acids (252) was made by Russian chemists in 1976 (253). Koga was probably the first to report a meaningful enantioselective Diels-Alder reaction (Scheme 105) in which the cyclopentadiene-methacro-lein exo adduct was obtained in 72% ee with the aid of 15 mol % of a menthol-modified aluminum chloride (254). The ee is highly dependent on the structures of the substrates, and asymmetric induction has not been observed with methyl acrylate as dienophile. Disproportionation... 

In order to form the activated complex required for the formation of product D, rotational changes of the less dipolar anti-form A to the more dipolar s jn-conformer B are necessary, to give an activated complex C with more parallel bond dipoles, which is thus more dipolar and better solvated than the reactant molecule. In agreement with this explanation is the observation that the reverse refro-Diels-Alder reaction exhibits no large solvent effect, since the activated complex C is quite similar to the reactant D [807], A very subtle solvent effect has been observed in the Diels-Alder addition of methyl acrylate to cyclopentadiene [124], The polarity of the solvent determines the ratio of endo to exo product in this kinetically controlled cycloaddition reaction, as shown in Eq. (5-43). The more polar solvents favour endo addition. 

K10 montmorillonites exchanged with different cations, dried at 120°C or calcined at 550°C, are used as catalysts in Diels-Alder reactions of methyl and (-)-menthyl acrylates with cyclopentadiene. In general, calcined clays give rise to better conversions and selectivities. Zr(IV) and specially Ti(IV) clays display the best catalytic activities. However, the best asymmetric induction is achieved with Cr(lll) and Ca(ll) calcined clays. Clays containing easily reducible cations behave differently due to the cyclopentadiene polymerization via radical cations. 

Clays [2] and zeolites [3] have been reported as good catalysts for Diels-Alder synthesis. Recently, we have studied the Diels-Alder cycloaddition between methyl acrylate (1) and cyclopentadiene (2) (Figure 1) and have shown that the solvent [4], the calcination of the solid [5] and the exchanged cation [6] play a decisive role. We now report the results obtained from the reactions of cyclopentadiene with methyl and (-)-menthyl acrylates, catalysed by K10 montmorillonites exchanged with different cations and dried at 120°C or calcined at 550°C. 

Evans s bis(oxazolinyl)pyridine (pybox) complex 17, which is effective for the Diels-Alder reaction of a-bromoacrolein and methacrolein (Section 2.1), is also a suitable catalyst for the Diels-Alder reaction of acrylate dienophiles [23] (Scheme 1.33). In the presence of 5 mol% of the Cu((l )-pybox)(SbF5)2 catalyst with a benzyl substituent, tert-butyl acrylate reacts with cyclopentadiene to give the adduct in good optical purity (92% ee). Methyl acrylate and phenyl acrylate underwent cycloadditions with lower selectivities. 

Diels-Alder reactions Neutral ionic liquids have been found to be excellent solvents for the Diels-Alder reaction. The first example of a Diels-Alder reaction in an ionic liquid was the reaction of methyl acrylate with cyclopentadiene in [EtNH3][N03] [40], in which significant rate enhancement was observed. Howarth et al. investigated the role of chiral imidazolium chloride and trifluoroacetate salts (dissolved in dichloromethane) in the Diels-Alder reactions between cyclopentadiene and either crotonaldehyde or methacroline [41]. It should be noted that this paper describes one of the first examples of a chiral cationic ionic liquid being used in synthesis (Scheme 5.1-17). The enantioselectivity was found to be < 5 % in this reaction for both the endo (10 %) and the exo (90 %) isomers. 

A similar study performed by Welton and co-workers studied the rate and selec-tivities of the Diels-Alder reaction between cyclopentadiene and methyl acrylate in a number of neutral ionic liquids [44]. It was found that endo. exo ratios decreased slightly as the reaction proceeded, and were dependent on reagent concentration and ionic liquid type. Subsequently, they went on to demonstrate that the ionic liquids controlled the endo. exo ratios through a hydrogen bond (Lewis acid) interaction with the electron-withdrawing group of the dienophile. 

The aqueous medium also has beneficial effects on the diastereoselectivity of the Diels-Alder reactions. The endo addition that occurs in the classical cycloadditions of cyclopentadiene with methyl vinyl ketone and methyl acrylate is more favored when the reaction is carried out in aqueous medium than when it is performed in organic solvents (Table 6.4) [2b, c]. 

Chloroaluminate ionic liquids (typically a mixture of a quaternary ammonium salt with aluminum chloride see Table 6.9) exhibit at room temperature variable Lewis acidity and have been successfully used as solvent/catalyst for Diels-Alder reactions [57]. The composition of chloroaluminate ionic liquids can vary from basic ([FMIM]C1 or [BP]C1 in excess) to acidic (AICI3 in excess) and this fact can be used to affect the reactivity and selectivity of the reaction. The reaction of cyclopentadiene with methyl acrylate is an example (Scheme 6.31). 

The Diels-Alder reaction of cyclopentadiene with methyl acrylate in methanol was studied by Berson et al. [72] under conventional conditions, and shown to give a mixture of the endo and exo isomers 48 and 49 (Scheme 4.26). 

It has been shown that Diels-Alder reactions can be carried out successfully in a range of ionic liquids [12], As highly ordered H-bonding solvents, ionic liquids have the potential for dramatic effects as solvents for such reactions. The range of polarities which can be spanned by varying the cation or anion may be exploited and it has been shown that the endo exo ratio for the reaction between cyclopentadiene and methyl acrylate (Scheme 7.5) is dependent on the polarity of the ionic liquid used [13] (Table 7.2). When the reactions were carried out in a range of ionic liquids, the endo exo values were shown to correlate with the polarity as measured by the Ej scale. 

Ohfune and coworkers78 used Diels-Alder reactions between 2-trimethylsilyloxy-l,3-butadiene (63) and acrylate esters 64 to synthesize constrained L-glutamates which they intended to use for the determination of the conformational requirements of glutamate receptors. The reactions between 63 and acrylate esters 64a and 64b did not proceed. Changing the ethyl and methyl ester moieties into more electron-deficient ester moieties, however, led to formation of Diels-Alder adducts, the yields being moderate to good. In nearly all cases, the cycloadducts were obtained as single diastereomers, which is indicative of a complete facial selectivity (equation 22, Table 1). Other dienes, e.g. cyclopentadiene and isoprene, also showed a markedly enhanced reactivity toward acrylate 64g in comparison with acrylate 64a. 

The asymmetric Diels-Alder reaction of cyclopentadiene with methyl acrylate lib has been studied using several types of catalysts. The asymmetric induction of various... 

This explains the experimentally confirmed predictions that polar solvents attenuate the endo-preference, while non-polar solvents increase the cwdo-selectivity of Diels-Alder reactions. The strong correlation between the polarity of the solvent and the endo/exo ratios in the Diels-Alder reaction led to the empirical polarity scale 2 = log endo/exo) using the reaction of cyclopentadiene with methyl acrylate as the standard144. The importance of solvent polarity has also been discerned on the basis of experimental142 and theoretical investigations145. Dependence on the polarizability was also noted146. 

Density functional theory has been used to investigate the Diels-Alder reactions of triazolinedione with s-cis- and. y-fran -butadiene. " Combined quantum mechanics-molecular mechanics calculations have been used to investigate the asymmetric Diels-Alder reaction of cyclopentadiene with the complex dienophiles AICI3-methyl acrylate and methoxyaluminium dichloride-acrolein.Equilibrium constants have been determined for the molecular complexes formed from 1-alkyl-1-(2-naphthyl)ethenes and 1-vinylnaphthalene with TCNE in C1(CH2)2C1 at 27.1 °C ... 

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