Diastereofacial selectivity Diels-Alder reactions

Highly uMtr-diastereofacial selective cycloaddition of isoprene (2) with 4-isopropyl-2-cyclohexenone allowed a short regiocontrolled and stereocon-trolled synthesis [13] of jS-cadinene and (y2-cadinene, Scheme 3.3). High anti-diastereofacial selectivity also occurs in the Diels-Alder reaction of optically active cyclohexenones 6-9 (Figure 3.2), readily available from the chiral pool, with open chain dienes [14-16]. Their cycloadducts are valuable intermediates in the synthesis of optically active sesquiterpenes in view of the easy conversion of the gem-dimethylcyclopropane and gem-dimethylcyclobutane in a variety of substituents. 

The catalyst played an important role in the asymmetric synthesis of Corey lactone based on high diastereofacial selective Diels-Alder reaction between chiral acrylate 37 and 5-benzyloxymethylcyclopentadiene [41] (Equation 3.9). The cycloadduct 38 was then converted into chiral Corey lactone [42] by a three-step procedure. 

It has been shown that the sulfinyl group present as chiral auxiliary either in dienophiles or in dienes is very useful for controlling the enantio- and diastereofacial selectivity in the asymmetric Diels-Alder reaction [43]. A wide variety of enantiomerically pure cyclohexadienedicarboxylates has been produced by cycloaddition of the sulfinylmaleate 39 with several dienes under catalyzed... 

Silica gel [11] or alumina [11a, 12] alone, or silica and alumina together modified by Lewis-acid treatment [13] and zeolites [14], have been widely used as catalysts in Diels-Alder reactions, and these solids have also been tested as catalysts in asymmetric Diels-Alder reactions [12,13b,14]. Activated silica gel and alumina at 140 °C were used [15] to catalyze the asymmetric cycloaddition of (-)-menthyl-N-acetyl-a, S-dehydroalaninate (3) (R = NHCOMe) with cyclopentadiene in the key step for synthesizing optically active cycloaliphatic a-amino acids. When the reactions were carried out in the absence of solvent, a higher conversion was obtained. Some results are reported in Table 4.5 and compared with those obtained by using silica and alumina modified by treatment with Lewis acids. Silica gel gives a reasonable percentage of conversion after 24 h with complete diastereofacial selectivity in exo addition. 

Coxon J. M., McDonald D. Q., Steel P. J. Diastereofacial Selectivity in the Diels-Alder Reaction Adv. Detailed React. Mech. 1994 3 131-166... 

Uncatalyzed Diels-Alder reactions between l-(trimethysiloxy)- or 1-acetoxy-l,3-butadiene and sugar-derived nitroalkenes having D-galacto or D-manno configurations proceed with complete regioselectivity. Diastereofacial selectivity is also complete with the D-galacto dieno-phile, whereas it is only moderate with the D-manno (Eq. 8.30).51... 

Okamura and coworkers151 studied the base catalyzed Diels-Alder reactions between 3-hydroxy-2-pyrone (224) and chiral l,3-oxazolidin-2-one based acrylate derivatives. Catalysis of the reaction between 224 and 225 by triethylamine gave fair to good de values, somewhat dependent on the solvent system used (equation 63, Table 7). Addition of 5% of water to the solvent isopropanol, for example, increased the de of the endo adduct 226 substantially. When the amount of water was increased, however, the triethylamine catalyzed reaction became less endo and diastereofacially selective, a small amount of exo 227 being obtained. Replacing triethylamine by the chiral base cinchonidine also improved the de, but now independently of the solvent system used. 

Cadogan and coworkers160 developed a fructose-derived l,3-oxazin-2-one chiral auxiliary which they applied in the Diels-Alder reactions of its iV-enoyl derivatives 246 with cyclopentadiene using diethylaluminum chloride as the Lewis acid catalyst. The reactions afforded mixtures of endo 247 and exo 248 (equation 68). The catalyst binds to the chiral dienophile in a bidentate fashion (co-ordination to both carbonyl groups). As a consequence, the dienophile is constrained to a rigid conformation which accounts for the almost complete diastereofacial selectivities observed. 

Garcia Ruano and colleagues165 studied the asymmetric Diels-Alder reactions of a-sulfinyl a,/l-unsaturated esters with several dienes. In the reactions with cyclopentadi-ene, both reactivity and stereoselectivity were increased in the presence of zinc dihalides acting as catalysts. TiCLt was found to be the most efficient catalyst, however, allowing reactions to be conducted at low temperatures. Different models were proposed to explain the diastereofacial selectivities observed. 

Brimble and coworkers172 reported the asymmetric Diels-Alder reactions between quinones 265 bearing a menthol chiral auxiliary and cyclopentadiene (equation 73). When zinc dichloride or zinc dibromide was employed as the Lewis acid catalyst, the reaction proceeded with complete endo selectivity, but with only moderate diastereofacial selectivity affording 3 1 and 2 1 mixtures of 266 and 267 (dominant diastereomer unknown), respectively. The use of stronger Lewis acids, such as titanium tetrachloride, led to the formation of fragmentation products. Due to the inseparability of the two diastereomeric adducts, it proved impossible to determine which one had been formed in excess. 

Chan and colleagues181 studied the efficiency of tricyclic sultam 285 in asymmetric Diels-Alder reactions which gave adducts like 286 (equation 79). Some of their results have been summarized in Table 14. The endo selectivities were high in all cases, whereas the diastereofacial selectivities depended on the catalyst and the reaction conditions employed. 

Crisp and Gebauer187 studied the endo selective Diels-Alder reactions of chiral dienes 295 with maleic anhydride. They found that the diastereofacial selectivity was dependent... 

Murray and colleagues199 developed some 2,5-diketopiperazines as new chiral auxiliaries and examined their asymmetric induction in the Diels-Alder reactions of their A-acryloyl derivatives with several dienes. Some of their results with dienophile 320 have been summarized in Table 19 (equation 89). When the benzyl group on 320 was substituted by an isopropyl or /-butyl group, the diastereofacial selectivity dropped dramatically. It was proposed that tv-tt stacking between the phenyl group and the electron-poor double bond provided a more selective shielding of one face of the double bond in this special case. 

Furthermore, regioselectivities89 as well as the diastereofacial selectivities90,91 may be increased in the presence of Lewis acids (Table 8). For instance, AICI3 OEt2 improves the ewrfo-selectivity of the reaction of cyclopentadiene and methyl acrylate from 82% to 98%87. The astonishing rate accelerations, the improved yields and higher selectivities make the Lewis acid catalysed Diels-Alder reaction one of the most important organic reactions. 

The Diels-Alder reaction between a 2-fluoroacrylic acid derivative of 8-phenyl-menthol (83) and cyclopentadiene shows high exo- and jr-diastereofacial selectivity (Scheme 30). The C(2) of endocyclic cross-conjugated 2-(acylamino)-l,3-dienes exerts excellent diastereofacial control on the Diels-Alder addition with electron-deficient dienophiles to produce octahydroquinolines. ... 

The Diels-Alder reactions of the chiral reagents A-allyl-o-butylanilide and A -(o-butylphenyl)-2-methylmaleimide proceed with high endo and diastereofacial selectivity. ... 

The diastereofacial selectivity of 2-azadienes with a stereogenic center attached to C-l in Diels-Alder reactions has been investigated (Scheme 63). The synthesis of monochloro derivatives 284 was readily achieved in excellent yields by halogenation of 139 with ALchlorosuccinimide. The... 

Saigo and co-workers reasoned that, by analogy, high levels of diastereofacial discrimination could be achieved in the Lewis acid-mediated Diels-Alder reaction of dienes with oxazolidinone 108-derived dienophiles. Indeed, excellent regioselectivities (endo. exo) and diastereoselectivities were reached in the Diels-Alder reaction of 109 with cyclic and acyclic dienes using Et2AlCl as the activator (Scheme 24.28).107 The selectivities obtained actually surpassed those reported with cis-1 -amino-2-indanol 1 as the chiral auxiliary (93% de) (see Scheme 24.16).82 The additional bulk... 

Diastereofacial-setective intramolecular Diels-Alder reactions. Trienecarbox-imides derived from ahiral oxazolidones undergo Lewis-acid-catalyzed intramolecular Diels-Alder reactions With high endo- and diastereofacial selectivity (endo/exo 100 1). 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

Poor (<4% de) to modest (56% de) amounts of diastereofacial selection is observed in the cycloaddition of nitrile oxides to optically active acrylates. The plan in each case, of course, was to use a chiral auxiliary which would preferentially shield one of the two ir-faces of the dipolarophile. Of the auxiliaries used, the sulfonamide esters derived from (+)-camphorsulfonyl chloride worked best, the menthyl esters derived from (-)-menthol the poorest (<4% de). As illustrated in Table 19, changes in both temperature and solvent had either no or little affect on the product ratios. Unlike Diels-Alder reactions, the addition of Lewis acids, specifically Et2AlCl, EtAlCh and TiCL, resulted in significant decreases in both the rate of cycloaddition and isolated yield, without an appreciable change in diastereomer ratio. ... 

The first example illustrating the use of a removable chiral auxiliary in IMDA reacticms was reported by Mukaiyama." The Diels-Alder reaction of (144) was slow and showed no diastereofacial selectivity. Conversion of (144) to the magnesium alkoxide (145), in which the dienophile is activated by chelaticm to the magnesium ion, however, increased the rate of cyclization and provided the indicated cycloadduct with 76% diastereomeric excess (rfe 88 12 mixture of diastereomers). 

In Lewis acid-promoted Diels-Alder reactions of cyclopentadiene with the acrylate of (iS )-ethyl lactate, good diastereofacial and endolexo selectivity are obtained with SnCU (84 16 endolexo = 18 1) and TiCU (85 15 endolexo = 16 1) [104]. It is interesting to note that boron, aluminum, and zirconium Lewis acids give the opposite diastereofacial selectivity (33 67 to 48 52). 

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