Cyclopentadienes with chiral catalysts

Brimble and coworkers176 studied the asymmetric Diels-Alder reactions of cyclopentadiene with chiral naphthoquinones 272 bearing different chiral auxiliaries. The highest endo and facial selectivities were obtained using zinc dichloride as the Lewis acid catalyst and (—)-pantolactone as the chiral auxiliary. Thus, the reaction between cyclopentadiene and 272 afforded a 98 2 mixture of 273 and 274 (equation 76). The chiral auxiliary was removed easily by lithium borohydride reduction. 

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. 

In 2005, Carretero et al. reported a second example of chiral catalysts based on S/P-coordination employed in the catalysis of the enantioselective Diels-Alder reaction, namely palladium complexes of chiral planar l-phosphino-2-sulfenylferrocenes (Fesulphos). This new family of chiral ligands afforded, in the presence of PdCl2, high enantioselectivities of up to 95% ee, in the asymmetric Diels-Alder reaction of cyclopentadiene with A-acryloyl-l,3-oxazolidin-2-one (Scheme 5.17). The S/P-bidentate character of the Fesulphos ligands has been proved by X-ray diffraction analysis of several metal complexes. When the reaction was performed in the presence of the corresponding copper-chelates, a lower and opposite enantioselectivity was obtained. This difference of results was explained by the geometry of the palladium (square-planar) and copper (tetrahedral) complexes. 

This procedure describes the preparation and application of an effective chiral catalyst for the enantioselective Diels-Alder reaction.11 The catalyst is derived from optically active 1,2-diphenylethylenediamine, the preparation of which (either antipode) was described in the preceding procedure. The aluminum-based Lewis acid also catalyzes the cycloaddition of crotonoyl oxazolidinones with cyclopentadiene,11 and acryloyl derivatives with benzyloxymethylene-cyclopentadiene. The latter reaction leads to optically pure intermediates for synthesis of prostaglandins.11... 

The Diels-Alder reaction of cyclopentadiene with /3-stannylpropynal is much faster than that with /3-alkylpropy-nals, and can be made enantioselective in the presence of a chiral Lewis acid catalyst (Equation (67)).213... 

The chiral Lewis acid catalyzed cycloaddition of methacrolein 310 to cyclopentadiene predominantly affording exo cycloadduct 322 together with some 323 has been extensively investigated. The application of menthoxyaluminum dichloride (324) as the chiral catalyst in this reaction represents one of the earliest examples of a chiral Lewis acid catalyzed Diels-Alder reaction206 (equation 90). The authors confirmed their results in 1987, but the ee was revised from 72% to 57%207. 

Corey and colleagues215 prepared chiral aluminum complexes from chiral bis(sulfona-mides) and trimethylaluminum. These were successfully applied in the cycloadditions of 3-acryloyl-l,3-oxazolidin-2-one (17a) with substituted cyclopentadienes. Thus, the reaction of 3-acryloyl-l,3-oxazolidin-2-one with 5-(benzyloxymethyl)cyclopentadiene (331) afforded 332 with 94% ee (equation 93). A transition state was proposed based on the X-ray structure of the chiral catalyst and on NMR data of the 1 1 complex between 333... 

Cross-linked polymers bearing IV-sulfonyl amino acids as chiral ligands were converted to polymer bound oxazaborolidine catalysts by treatment with borane or bromoborane. In the cycloaddition of cyclopentadiene with methacrolein, these catalysts afforded the same enantioselectivities as their non-polymeric counterparts238. 

Reilly and Oh explored the asymmetric induction of chiral catalysts derived from bis(dichloroborane) 397 in the cycloaddition of cyclopentadiene with a-bromoacrolein and methacrolein. /V-Tosyltryplophan (394) and chiral diols 395 and 396 were employed as chiral ligands246,247. The application of chiral iV-tosyltryptophan afforded the best results (equation 118, Table 22). 

The cationic aqua complexes of the C2-symmetric trans-chelating tridentate ligand 447 proved also highly effective chiral catalysts. The complexes involving the metal(II) perchlorates of iron, cobalt, nickel, copper and zinc produced the main endo adduct of cyclopentadiene and N - aery loy 1-1,3 -oxazo I i din -2 -one with very high ee values281. 

Several chiral lanthanide(III) Lewis acid catalysts, derived from chiral binaphthols, have been used in the cycloaddition reactions of cyclopentadiene with substituted iV-acryloyl-1,3-oxazolidin-2-ones. A catalyst derived from ytterbium triflate, (R)-binaphthol... 

Some chiral 1,3,2-dioxastannolanes were used as catalysts in asymmetric Diels-Alder reactions of cyclopentadiene with methyl acrylate <90JCR(S)278>. A-Alkenyl- and -cycloalkenyl 1,3,2-oxaza-stannolanes, generated in situ from chiral amino alcohols, gave optically active 2-substituted aldehydes and ketones in modest to high chemical and optical yields after alkylation with methyl acrylate or acrylonitrile (which is usual for enamines) and subsequent hydrolysis <85CC504,85JOC3863>. 

Two asymmetric Diels-Alder approaches to analogues like 830 and 831 have been described. In the hrst case, chiral catalysts were employed for an enantiose-lective Diels-Alder reaction, but unfortunately, none of the chiral catalysts showed any enantioselectivity upon analysis of the reaction mixtures. Alternatively, a chiral oxazolone 840 incorporating a menthyl carbonate at C-4 was prepared and used as a dienophile with cyclopentadiene. In this case, the exo/endo ratio was 60 40 but no signihcant endo or exo diastereoselectivity was obtained (Scheme 7.258). ° ... 

With Binaphthol/M(OTf)3 Complexes (M = Yb, Sc) A chiral ytterbium triflate, derived from Yb(OTf)3, (R)-binaphthol, and a tertiary amine, has been applied to the enantioselective Diels-Alder reaction of cyclopentadiene with crotonoy 1 oxazolidinones. Among various tertiary amines, c/s-1,2,6-trimethyl piperidine was found to be highly effective [44] (Eq. 8 A.23). The unique structure of such chiral Yb catalysts is characterized by hydrogen bonding between the phenolic hydrogens of (R)-binaphthol and the nitrogens of tertiary amines. 

With Chiral Al Complexes Chiral bis(silyl)binaphthol-modified aluminum catalyst, which is originally developed for asymmetric hetero-Diels-Alder reaction [50], is successfully applied to asymmetric Diels-Alder reaction of cyclopentadiene with methyl acrylate or methyl propio-late [51 ] (Eq. 8A.28). The latter is a rather rare example in the literatures. 

Measurements of molar rotation showed that this parameter is almost proportional to the number of chiral binaphthyl units and the molar rotation per binaphthyl unit varies only slightly. On catalysis of the Diels-Alder reaction of cyclopentadiene with 3-[(E)-but-2-enoyl]oxazolidin-2-one the branched catalysts 7 and 8 showed an approximately 25% higher reactivity than the monofunctional catalyst 6 however, the former led to just a slight improvement of ee and endo-selectivity compared to 6. It is thus inappropriate to speak of a dendritic effect on catalysis, although one does indeed exist in relation to the chiroptical properties. 

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 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. 

Ketene acetal sulfoxide 30 has been used as a chiral ketoester ketene acetal equivalent, because it undergoes a ready enantiocontrolled reaction with cyclopentadiene at -78°C in the presence of BF3 yielding a 96 4 mixture of endo and exo adducts with complete n-facial selectivity (Scheme 15) [44]. The endo selectivity decreased with other catalysts, but the 7r-facial selectivity remained complete, whereas under thermal conditions (139 °C, 15 h) a mixture of the four possible adducts was obtained. The adduct 31 was transformed into (+)-(lRy4R)-norbornenone in a four-step sequence. 

Cationic ansa metallocenes can be utilized as chiral catalysts in Diels-Alder reactions. For example, in the presence of the cationic zirconocene complex [(ebthi)Zr(Ot-Bu) thf]+, the [4 + 2] cycloaddition of acrolein and cyclopentadiene proceeds efficiently to afford endo and exo cycloadducts (equation 71). In reactions in which methyl acrylate is used as the dienophile, cycloadditions occur with lower levels of enan-tioselection (23% ee), but with significantly higher degrees of diastereoselectivity (17 1 endo, exo). In these processes, recent studies demonstrated the great influence of chiral metallocene structure and the dramatic solvent effect. ... 

Diels-Alder Reactions. It has been demonstrated that the ligand-metal complexes derived from (5,5)-/-Bu-box and a mild Lewis acid such as Cu(OTf)2 are very efficient chiral catalysts for the Diels-Alder reaction with cyclopentadiene and substituted acylimide derivatives. Among various ligands examined, the (5,5)-/-Bu-box ligand consistently provided a very high level of endo/exo selectivity as well as endo enantioselectivity (90-98% ee with 5-10 mol % catalyst) and yield (82-92%) with a number of substituted dienophiles. 

Helmchen and co-workers [13] independently achieved similar results with catalysts of CAB 3 derived from valine (R = /-Pr). When R is 2,4,6-trimethylphenyl, the cycloaddition of crotonaldehyde and cyclopentadiene occurs with 72 % ee exo endo = 3 97) in the presence of 0.2 equiv. chiral catalyst. More recently, the same authors systematically investigated the influence of different experimental conditions on the enantioselectivity [15]. Improved enantioselectivity was obtained in THE or by addition of THE (ee up to 86 %). A transition-state model is proposed for prediction of the absolute configuration of the adducts (Eig. 2). In this model, the R group directs the R S02 group to the opposite side of the ring, where the latter group again participates in trans attack on boron. The conformation of the complexed enal has been determined to be s-cis, as has the coordination of carbonyl to boron syn to H. This model correctly predicts the outcome of all the examples studied. 

Mukaiyama and co-workers have reported that prolinol derivatives combined with BBrs produce promising catalysts for some Diels-Alder reactions [26]. Methacrolein and cyclopentadiene, for example, afford the exo adduct (exoiendo > 99 1) in 97 % ee (reaction at -78 °C in dichloromethane with 20 mol % catalyst). The chiral catalyst is believed to be the HBr adduct salt of the amino boron derivative (Eq. 26). 

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 first examples of an asymmetric Diels-Alder reaction of a non-chiral diene and a dienophile catalyzed by a chiral Lewis acid were reported by Koga and coworkers in 1979 (Sch. 1 and 16) [3]. The catalysts 4,142 and 143 were prepared from (-)-menthol, (+)-neomenthol and (+)-borneol. The reaction of methacrolein and cyclopentadiene mediated by catalyst 4 gave a 98 2 mixture of exo to endo products and upon separation of these diastereomers by chromatography the exo product 3 was obtained in 69 % yield and 72 % ee. The exo .endo ratios for the other reactions in Sch. 16 were not reported. Low asymmetric induction was observed for acrolein and methyl acrylate with all three catalysts. Moderate induction was observed in the reaction of methacrolein with catalyst 4, and with catalyst 142, but in the latter the enantiomer of 3 was the predominant product. The reaction of methyl acrylate with cyclopentadiene mediated by 10 mol % catalyst 4 was also reported by Kobayashi, Matsumura and Furukawa to give the cycloadduct 141 in 2.9 % ee at 30 °C [37]. These workers also reported that catalyst 4 will give optically active product from the reaction of cyclopentadiene and acrylonitrile, although the optical yield was not determined. 

The reaction of methyl acrylate and cyclopentadiene has been carefully examined by Ketter, Glahsi, and Herrmann with chiral aluminum catalysts prepared from the seventeen chiral diols and /9-hydroxysulfonamides shown in Table 12 [47]. The catalysts were prepared in-situ by reacting the ligand with one equivalent of di-isobutyl-aluminum chloride in dichloromethane at room temperature for 1 h. The standard conditions for the screening of these reactions were 10 mol % catalyst in dichloromethane and 0 to 5 °C, as indicated in Sch. 22. 

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