Cyclopentadienes with chiral dienophiles

A variety of solid Lewis and Br0nsted acids has been shown to catalyze Diels-Alder reactions. In several instances the results obtained with heterogeneous catalysts were better than those with homogeneous Lewis acid catalysts. Most of the reported reactions of interest in the synthesis of fine chemicals were catalyzed by (modified) zeolites, clays, alumina, or silica. Catalysts with interesting properties were obtained when support materials such as zeolites, alumina, or silica were treated with Lewis acids. These catalysts were moderately selective in diastereo-selective Diels-Alder reactions with chiral dienophiles and induced enantioselec-tivity (up to 31 % e. e.) in the reaction of cyclopentadiene with methacrolein after treatment with chiral derivatives. Excellent enantioselectivity in this reaction (up to 95 % e. e.) was observed with a polymer-supported chiral oxazaborolidinone. Because of their facile recovery and recycling, we expect that solid-acid catalysts will find increasing use in Diels-Alder reactions in the future. 

Furanones are a class of chiral dienophiles very reactive in thermal cycloadditions. For example, (5R)-5-(/-menthyloxy)-2-(5H)-furanone (28) underwent Diels Alder reaction with cyclopentadiene (21) with complete re-face-selectivity (Equation 2.10), affording a cycloadduct which was used as a key intermediate in the synthesis of dehydro aspidospermidine [27]. 

The chiral catalyst 142 achieves selectivities through a double effect of intramolecular hydrogen binding interaction and attractive tt-tt donor-acceptor interactions in the transition state by a hydroxy aromatic group [88]. The exceptional results of some Diels-Alder reactions of cyclopentadiene with substituted acroleins catalyzed by (R)-142 are reported in Table 4.21. High enantio- and exo selectivity were always obtained. The coordination of a proton to the 2-hydroxyphenyl group with an oxygen of the adjacent B-0 bond in the nonhelical transition state should play an important role both in the exo-endo approach and in the si-re face differentiation of dienophile. 

Chiral dienophiles, prepared from an aldehyde and asparagine in water followed by reacting with acryloyl chloride, reacted with cyclopentadiene at room temperature in water or ethanol-water to provide cycloadducts diastereoselectively and chiral products upon separation and hydrolysis (47-64% ee for the endo isomers endo/exo 82 18) (Eq. 12.18).61... 

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. 

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... 

With Chiral Bis(oxazoline)/Mg Complexes A chiral bis(oxazoline)/MgI2 complex has been utilized for the enantioselective Diels-Alder reaction of cyclopentadiene and ethyl 2-benzoylacrylate that acts as a two-point binding dienophile [49] (Eq. 8A.27). This reaction proceeds with virtually complete endo/exo selectivity (>99 1). 

The reaction of methacrolein with cyclopentadiene catalyzed by a chiral menthoxyaluminum complex gives adducts with ee s of up to 72%, but with other dienophiles little, if any, induction was noted.9495 A chiral cyclic amido aluminum complex 2 catalyzes the cycloaddition of cyclopentadiene with the fran.v-crotyl derivative 3 in good yield and enantioselectivity (Scheme 26.2).47 This chiral catalyst can also be easily recovered. 

Diphenyl-BINOL-derived chiral aluminum reagents are prepared in situ by addition of Ethylaluminum Dichloride or Diethylaluminum Chloride to 3,3 -diphenyl-BINOL. These chiral aluminum reagents promote the enantioselective Diels-Alder reaction of cyclopentadiene with the oxazolidone dienophile (eq 14). Endo products are obtained with a high level of asymmetric induction (>90% ee) however, a stoichiometric amount of the Lewis acid is required. The preparation and use of a C3 symmetric BINOL-derived boronate has been reported (eq 15). BINOL-B(OAr)3 complexes have recently been developed for the asymmetric Diels-Alder reaction with imines (eq 16). ... 

Diels-Alder Reactions. Reagent 1 is useful as an efficient chiral dienophile in asymmetric Diels-Alder reactions. Reaction of 1 with cyclopentadiene in the presence of a Lewis acid occurs with high stereoselectivity. Reaction with 6-methoxy-l-vinyl-3,4-dihydronaphthalene in the presence of EtAlCh proceeds with... 

The four possible transition-state structures for the Lewis acid-promoted Diels-Alder reaction of cyclopentadiene with propynal are depicted in Fig. 7. In the chiral Lewis acid-promoted reaction, the enantiomeric excess of an adduct originates in the enantiofacial selectivity of cyclopentadiene, which has prochiral reactive centers. The enantioselective pathway presupposes three characteristics (i) the chiral Lewis acid must sterically shield one enantioface of the coordinated propynal because the open acetylenic jr-face in the chiral catalyst-dienophile complex approaches one face of... 

The possibility that metallocenes might function as Lewis acids in Diels-Alder reactions was probed with ferrocenium hexafluorophosphate [184]. The answer is affirmative the cycloadditions studied include methacrolein, crotonaldehyde, and methyl vinyl ketone as dienophiles and butadienes and cyclopentadienes as diene components. Yields are in the range 60-80 % with reaction times of 3-36 h at 0 to 20 °C. Fair to good yields were also obtained in reactions of isoprene and cyclopentadiene with acrolein and methyl vinyl ketone in the presence of 1 % [Pd(PPh3)2(MeCN)2](BF4)2 (in CH2CI2, room temperature). Methyl acrylate resulted in low yields, and chiral modification with (5)-BINAP is reported to give the cycloadducts with modest enantioselectivity [164]. 

The chiral triflate complex (ebthi)Ti(OTf)2 has been synthesized by the reaction of the parent dichloride with AgOTf and used to catalyze the Diels-Alder reaction of cyclopentadiene with oxazolidinone-derived dienophiles. The level of asymmetric induction is dramatically affected by solvent polarity and this behavior can be partially explained with reference to the results of variable-temperature NMR studies.1665... 

The cycloaddition of functionalized cyclopentadiene and dienophile 83 was better performed by use of an entirely different, non-phenoxide-type aluminum complex (Scheme 6.53). Thus a chiral catalyst endowed with the more electron-with-drawing bis (sulfonamide) ligand was explored by Corey and coworkers [73]. The reaction of the trons-crotyl derivative 83 and cyclopentadiene with 20 mol% 84 as catalyst at -78 °C for 16 h provided adduct 85 in 88% yield and 94% ee. The ad-... 

Fukuzawa and coworkers reported the rare earth (III) salt-catalyzed asymmetric Diels-Alder reaction of cyclopentadiene with a chiral dienophile in SCCO2 [112]. The Diels-Alder reaction in SCCO2 proceeded rapidly to give the corresponding adducts with higher diastereoselectivities than those in CH2CI2 (Scheme 7.41). 

These first cycloadditions are only complete after 72 h at 60°C. When partners are more reactive and the cycloaddition can be catalysed by Lewis acids, it is possible to work at -78°C. Under these conditions, it may be possible to observe high asymmetric induction. Reaction (8.4) of cyclopentadiene with an acrylate derivative of 5-0-trimethylsilyl-a-D-xylofuranose carried out at -78°C in dichloromethane in the presence of TiCl4 gives exclusively the endo adduct ( / , 2 R). This is explained by the formation of an intermediate complex which contains both the dienophile and Lewis acid attached to the chiral sugar inductor (Kunz etal. 1987). 

The application of cyclic carbohydrate derivatives as chiral dienophiles has been investigated by several groups. 2,3-Dideoxy-DL-pent-2-enopyranose-4-ulose (17) in the thermal [4+2] cycloaddition to the acyclic dienes 18a-c is reported to produce mixtures of cycloadducts 19a-c epimeric on the hemiacetal center with an all-as-configuration of the other newly formed bonds. The reaction with cyclopentadiene (10) and 1,3-cyclohexadiene (11) yields adducts 20 as the sole products31. It should be emphasized that epimerization may occur on the anomeric center during the protection step (as an equilibrium process), thus leading to a mixture of adducts, while the endolexo ratio remains the same. 

Diels-Alder reactions of cyclopentadiene with methyl acrylate [19], (-)-menthyl acrylate, or other chiral dienophiles [20-23] catalyzed by cation-exchanged KIO montmorillonites were thoroughly investigated by Mayoral and co-workers. The structures of the chiral dienophiles are depicted in Figure 1. Moderate diastereo-selectivities were obtained with (-)-menthyl acrylate (54 %) and (7 )-f -acryloyl-pantolactone (53 %) in reactions catalyzed by zinc(II)-exchanged KIO montmoril-lonite at —20 °C. 

Figure 1. Structures of chiral dienophiles investigated by Mayoral et al. in Zn(II)-KlO-catalyzed Diels-Alder reactions with cyclopentadiene. Reference numbers are given in square parentheses.

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