Cyclopentadiene reaction with acrylates

Clay-catalyzed asymmetric Diels-Alder reactions were investigated by using chiral acrylates [10]. Zn(II)- and Ti(IV)-K-10 montmorillonite, calcined at 55 °C, did not efficiently catalyze the cycloadditions of cyclopentadiene (1) with acrylates that incorporate large-size chiral auxiliaries such as cA-3-neopentoxyisobornyl acrylate (2) and (-)-menthyl acrylate (3, R = H) (Figure 4.1). This result was probably due to diffusion problems. 

The same reaction in cyclopentadiene gives a mixture of two of the fused products 6.368 and a single bridged product 6.369. The fused products are similar to those from the reaction with acrylate, and the bridged product is allowed, whether one takes the frontier orbitals as HOMO jmethyienemethane)/ LUMO(Cycl0pentadiene) or the other way round as illustrated. One hint that the other way round is important is the endo-like selectivity, which might follow from the secondary interaction shown as dashed lines.873 874... 

Q 1. Cyclopentadiene reacts with acrylic ester to give products of Diels—Alder reaction. What are the interacting frontier molecular orbitals ... 

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. 

The Diels-Alder reaction of a diene with a substituted olefinic dienophile, e.g. 2, 4, 8, or 12, can go through two geometrically different transition states. With a diene that bears a substituent as a stereochemical marker (any substituent other than hydrogen deuterium will suffice ) at C-1 (e.g. 11a) or substituents at C-1 and C-4 (e.g. 5, 6, 7), the two different transition states lead to diastereomeric products, which differ in the relative configuration at the stereogenic centers connected by the newly formed cr-bonds. The respective transition state as well as the resulting product is termed with the prefix endo or exo. For example, when cyclopentadiene 5 is treated with acrylic acid 15, the cw fo-product 16 and the exo-product 17 can be formed. Formation of the cw fo-product 16 is kinetically favored by secondary orbital interactions (endo rule or Alder rule) Under kinetically controlled conditions it is the major product, and the thermodynamically more stable cxo-product 17 is formed in minor amounts only. 

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 ene reaction of fuUerene (C o) with 3-methylene-2,3-dihydrofuran gives an easily isolated addition product in good yield <96JOC2559>. There is a continuous need for chiral acrylate esters for asymmetric Diels-Alder reactions with high diastereoselectivity. Lewis acid promoted Diels-Alder reactions of acrylate esters from monobenzylated isosorbide 28 (or isomannide) and cyclopentadiene provided exclusively e db-adducts with good yields and high diastereoselectivity <96TL7023>. 

Scott Oakes et al. (1999a, b) have shown how adoption of SC conditions can lead to a dramatic pressure-dependent enhancement of diastereoselectivity. In the case of sulphoxidation of cysteine derivatives with rert-butyl hydroperoxide, with cationic ion-exchange resin Amberlyst-15 as a catalyst, 95% de was realized at 40 °C and with SC CO2. By contrast, with conventional solvents no distereoselectivity was observed. Another example is the Diels-Alder reaction of acrylates with cyclopentadiene in SC CO2 at 50 °C, with scandium tris (trifluoromethanesulphonate) as a Lewis acid catalyst. The endoiexo ratio of the product was as high as 24 1, while in a solvent like toluene it was only 10 1. 

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 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... 

Diels-Alder catalyst.2 The acrylates (4) of three chiral alcohols (1-3) have been found to undergo asymmetric Diels-Alder reactions with cyclopentadiene (equation I) in the presence of a Lewis acid catalyst. For this purpose, catalysts of the type TiCl2(X2) are superior to TiCl4 because they do not promote polymerization of the acrylate. The final products (6) all have the enrfo-orientation the configuration (R) or (S) depends upon the chiral alcohols. Those derived from 1 all have (S)-configuration ... 

Asymmetric Diels-Alder reactions. The acrylate of (+ )-l is markedly superior to ( —)-menthyl acrylate in effecting asymmetric induction in Diels-Alder reaction with cyclopentadiene (Lewis acid catalysis, equation I). A chiral intermediate in Corey s prostaglandin synthesis was obtained by the reaction of (-1- )-8-phenylmenthyl acrylate with a cyclopentadiene derivative.1... 

Asymmetric Diels-AUer reactions The observation that simple acyloxy-boranes such as H2BOCOCH=CH2, prepared by reaction of BH3 with acrylic acid, can serve as Lewis acid catalysts for reactions of the a,P-unsaturated acids with cyclopentadiene (15, 2) has been extended to the preparation of chiral acyloxy-boranes derived from tartaric acid. The complex formulated as 3, prepared by reaction of BH3 with the monoacylated tartaric acid 2, catalyzes asymmetric Diels-Alder reactions of a,P-enals with cyclopentadiene with high enantioselectivity. The process is applicable to various dienes and aldehydes with enantioselectivities generally of 80-97 % ee. 

The rather low reactivity of the 3-p-tolylsulfinyl acrylates (they do not react with furan even under forcing conditions) prompted the search for more reactive dienophiles. In this context, pyridylsulfinyl derivatives proved to be more efficient than the arylsulfinyl ones. Thus, menthyl-3-(2-pyridylsulfinyl)propenoates 14a and 14b were prepared from (+)-menthyl propiolate in low yields [34]. Their reactions with cyclopentadiene proceed smoothly in the presence of Et2AlCl at -70°C to afford just one endo diastereoisomer 15a or 15b [35] (in the absence of the catalyst the 7r-facial selectivity for the endo approach was lower than that observed for the p-tolylsulfmyl derivatives [10c]). These compounds were transformed into 16a or 16b [36] respectively (Scheme 8), both allowing the synthesis of the bicyclic lactone 17 (known as Ohno s lactone), a key intermediate in Ohno s synthesis of (-)-aristeromycin and (-)-neplanocin A [37]. 

Recently, Koizumi et al. reported that the use of high pressures allows exclusion of Lewis acids (which are not compatible with many dienes and/or adducts) in the cycloadditions of acrylates [43]. Thus, methyl 3-alkylsulfinyl acrylate 29 is able to react with cyclopentadiene, furan, and 2-methoxyfuran at 12.6 Kbar (Scheme 14). Both 7r-facial and endo/exo selectivities are very high in reactions with cyclopentadiene (only one adduct was obtained), whereas with furan derivatives the endo/exo selectivity is clearly lower. In reactions with cyclopentadiene it could be established that high pressures do not have a significant influence on the diastereoselectivity. The transformation into (-)-COTC of the major adduct obtained from 2-methoxyfuran was carried out in order to confirm its absolute configuration. 

The fact that the rate of some Diels-Alder [4 + 2] cycloaddition reactions is affected, albeit only slightly, by the solvent was used by Berson et al. [52] in establishing an empirical polarity parameter called Q. These authors found that, in the Diels-Alder addition of cyclopentadiene to methyl acrylate, the ratio of the endo product to the exo product depends on the reaction solvent. The endo addition is favoured with increasing solvent polarity cf. Eq. (5-43) in Section 5.3.3. Later on, Pritzkow et al. [53] found that not only the endojexo product ratio but also the absolute rate of the Diels-Alder addition of cyclopentadiene to acrylic acid derivatives increases slightly with increasing solvent polarity. The reasons for this behaviour have already been discussed in Section 5.3.3. Since reaction (5-43) is kinetically controlled, the product ratio [endo]l[exo] equals the ratio of the specific rate constants, and Berson et al. [52] define... 

Cycloadditions. The asymmetric Diels-Alder reaction of phenylmenthyl acrylate with 5-benzyloxymethyl-cyclopentadiene in the presence of Aluminum Chloride produces an 89% yield of the endo cycloadduct (eq 1), accompanied by 7% of the exo adduct. This provides a useful intermediate for the preparation of various prostaglandins. The Tin(IV) Chloride and Titanium(IV) Chloride catalyzed reactions with Cyclopenta-diene deliver a mixture of endo and exo adducts in 89% de, and 90% de, respectively (eq 2). The TiCU reaction gives an 89 11 endo. exo ratio, while the SnCU reaction gives an 84 16 endoiexo ratio. From a practical point of view, the titanium and tin catalysts are the best of the various Lewis acids surveyed. The use of TiCl4 is also the most effective for the reaction of the acrylate... 

The fust use of an asymmetric Diels-Alder reaction in enantioselective synthesis, reported by Corey and Ensley (1975), involved both diene and dienophile face differentiations (Scheme 74). Addition of 5-(methoxymethyl)cyclopentadiene (304) to acrylic acid (305a) proceeded endo selectively and anti with respect to the diene substituent. Consequently, the relative configuration of the four new chiral centers in (30fo) was determined and, of four possible diastereoisomers, one was formed selectively. As expected, the diene added at the same rate to the two enantiotopic dienophile ir-faces, affording a 1 1 mixture of the enantiomers (lf )-(306a) and (15)-(306a). 

About 10 years later the catalytic use of boron derivatives was again investigated by Kaufmann et al. Compounds of the type RBBr2 (R = pinanyl) catalyze the Diels-Alder reaction at -78 °C with low ee (Eq. 3) [4]. Modified isopinocamphenyl dibro-moborane, which has been synthesized since then, gives better results in the reaction of cyclopentadiene and methyl acrylate (Eq. 4) [5]. 

The Diels-Alder reaction of cyclopentadiene and methyl acrylate proceeds smoothly at -78 °C in the presence of 10 mol % of catalysts (7 )-23 to give the endo adduct in high yield with > 99 % diastereoselectivity (Eq. 37). Catalyst 23b resulted... 

An approach to lactone [12] similar in concept to that just described, but not requiring a resolution, involved asymmetric Diels-Alder reaction of (benzyloxymethyl)cyclopentadiene [21] with the chiral ester of acrylic add and 8-phenylmenthoI (22), The adduct [22] was obtained in undetermined but apparently quite high e.e. Oxidation of the ester enolate of [22], followed by lithium aluminum hydride reduction, gave diol [23] as an... 

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