Esters, acrylate reaction with cyclopentadiene

Asymmetric Diels-Alder reactions of a, ft-unsaturated acids.2 The acrylate ester (2) of this alcohol (1) undergoes Lewis acid-catalyzed reactions with cyclopentadiene in >97 3 diastereoselectivity. 

The acrylate 383, derived from l,4 3,6-dianhydro-D-glucitol, undergoes Diels Alder reactions with cyclopentadiene giving >99% endo products, with a 92% selectivity in favour of the S-endo product 384. The analogous reaction of the l,4 3,6-dianhydro-D-mannitol-derived ester, catalysed by ethylaluminium dichloride, also gives >99% endo products, but with a 90% diastereoselectivity in favour of the R-endo product. 

Enantioselective D-A reactions of chiral esters and amides of acrylic acid can be achieved using achiral Lewis acid such as TiCU. After the reaction, enantiomeric pure carboxylic acid can be recovered on hydrolysis. For example, the reaction of acrylic acid with cyclopentadiene using chiral a-hydroxy ethyl propionate 95a as chiral auxiliary in the presence of TiCU gives only one enantiomeric product in large excess (93 %) [82]. The chiral auxiliary 95a reacts with dienophile to produce a chiral ester 95, which participates in the reaction with cyclopentadiene. 

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>. 

Carbohydrates have found widespread use as chiral auxiliaries in asymmetric Diels-Al-der reactions156. A recent example is a study conducted by Ferreira and colleagues157 who used carbohydrate based chiral auxiliaries in the Lewis acid catalyzed Diels-Alder reactions of their acrylate esters 235 with cyclopentadiene (equation 66). Some representative results of their findings, including the ratios of products 236 and 237, have been summarized in Table 9. The formation of 236 as the main product when diethylaluminum chloride was used in dichloromethane (entry 3) was considered to be the result of an equilibrium between a bidentate and monodentate catalyst-dienophile complex. The bidentate complex would, upon attack by the diene, lead to 236, whereas the monodentate complex would afford 236 and 237 in approximately equal amounts. The reversal of selectivity on changing the solvent from dichloromethane to toluene (entry 2 vs 3) remained unexplained by the authors. 

Nieman and Keay198 reported the use of c/.v,c/s-spiro 4,4]nonanc-1, 6-diol as a new chiral auxiliary to be used in asymmetric Diels-Alder reactions. Their best results in a series of reactions between chiral acrylates and cyclopentadiene were obtained when the pivalate ester of ds,ds-spiro[4,4]nonane-l,6-diol was used as the chiral auxiliary. When 318 was treated with cyclopentadiene, the expected endo adduct 319 was obtained with more than 97% de (equation 88). 

For the Diels-Alder reaction, polymer-bound acrylic acid ester (73) was treated with cyclopentadiene. The cycloaddition product (74) was formed with an endo/exo ratio of 2.5 1 and with quantitative conversion. The subsequent enzymatic release delivered the corresponding alcohols (72, 75) in high yield and purity. 

Simple diastereoselectivity may also occur in Diels-Alder reactions between electron-poor dienophiles and cyclopentadiene (Figure 15.30). Acrylic acid esters or fraus-crotonic acid esters react with cyclopentadiene in the presence or absence of A1C13 with substantial selectivity to afford the so-called emfo-adducts. When the bicyclic skeleton of the main product is viewed as a roof the prefix endo indicates that the ester group is below this roof, rather than outside (exo). However, methacrylic acid esters add to cyclopentadiene without any exo.endo-selectivity regardless whether the reaction is carried out with or without added A1C13 (Figure 15.30, bottom). 

The reaction of several different acrylate esters with cyclopentadiene was examined for the optimum catalyst derived from ligand 207 and under optimum conditions (-10 °C Sch. 23). Asymmetric induction was found to increase with the size of the substituent of the ester to the extent that 81 % ee could be obtained with the /-butyl ester, although the reaction was quite slow (15 % yield after 164 h). This is one of very few examples of investigation of the effect of the size of an ester substituent on asymmetric induction. 

The Diels-Alder reaction of enantiomerically pure chiral acrylic esters with cyclopentadiene leads to a pair of diastereomers. Their ratio depends strongly on the choice and amount of Lewis acid catalyst (Scheme 8). While titanium tetrachloride leads preferentially to the (2/ )-diaslcrcomer with high selectivity, ethyl aluminium dichloride gives the (2S)-diastereomer in only 56% de. 

Several studies have indicated that Diels-Alder reactions catalyzed by Lewis acids are much more likely to give high diastereoselectivity than are uncatalyzed reactions. " In one study, the results of which are shown in Table 11.4, several optically active acrylate esters were allowed to react with cyclopentadiene in the presence or absence of Bp3-OEt2 catalyst. The product of the uncatalyzed reactions showed only about 10% optical purity after hydrolysis while the catalyzed reactions... 

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. 

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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