Diels cyclopentadiene with acrolein

Diels-Alder catalyst. The Diels-Alder reaction of cyclopentadiene with acrolein (equation I) catalyzed by BF3 etherate gives a mixture of endo- and exoadducts in the ratio 9 1. The endo-selectivity is improved by use of trimethylalu-minum. Introduction of a more bulky group on aluminum by use of DAD results... 

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]. 

In 1979, Koga and coworkers disclosed the first practical example of a catalytic enantioselective Diels-Alder reaction [44] promoted by a Lewis acidic complex, presumed to be menthoxyaluminum dichloride (1), derived from menthol and ethylaluminum di chloride, whose structure remains undefined [45]. This complex catalyzed the cycloaddition of cyclopentadiene with acrolein, methyl acrylate, and methacrolein with enantioselectivities as high as 72% ee. Oxidation of 2 (predominantly exo) followed by recrystallization actually lowered the ee ... 

Chemoselective Diels-Alder Reaction with a,fi-Unsaturated Aldehydes and Ketones. Br0nsted acid (1) is an effective catalyst for the chemoselective Diels-Alder reaction of cyclopentadiene with acrolein and ethyl vinyl ketone (eq 3). The reaction catalyzed by (1) proceeds smoothly and shows high chemoselectivity for ethyl vinyl ketone, although the catalytic activities of methanesulfonic acid and p-toluenesufibnic acid are poor. However, some Lewis acids such as SnCLj and B(C6Fs)3 show high chemoselectivity for acrolein. 

Lanthanide /3-diketonates have been used as catalysts in Diels-Alder reactions. The first example of a lanthanide-catalyzed cycloaddition was the dimerization of spiro[2.4]hepta-4,6-diene by [Eu(tfn)3] (Morrill et al., 1975) (scheme 2). In the absence of the europiitm(lll) complex no dimerization took place. Because of the mild experimental conditions, this catalyst has potential in Diels-Alder reactions where acid labile components are combined. An example is the cycloaddition of cyclopentadiene with acrolein (Danishefsky and Bednarski, 1985). 

Acrolein a.s Dienophile. The participation of acrolein as the dienophile in Diels-Alder reactions is, in general, an exothermic process. Dienes such as cyclopentadiene and l-dieth5laniino-l,3-butadiene react rapidly with acrolein at room temperature. 

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. 

Density functional theory has been used to investigate the Diels-Alder reactions of triazolinedione with s-cis- and. y-fran -butadiene. " Combined quantum mechanics-molecular mechanics calculations have been used to investigate the asymmetric Diels-Alder reaction of cyclopentadiene with the complex dienophiles AICI3-methyl acrylate and methoxyaluminium dichloride-acrolein.Equilibrium constants have been determined for the molecular complexes formed from 1-alkyl-1-(2-naphthyl)ethenes and 1-vinylnaphthalene with TCNE in C1(CH2)2C1 at 27.1 °C ... 

Yamamoto has disclosed that another binaphthol-derived complex is an effective catalyst for enantioselective Diels-Alder reactions of aldehydes and cy-clopentadiene (Scheme 45). Azeotropic removal of 2-propanol from a mixture of ligand 57 and Ti(OiPr)4 affords a Lewis acid capable of catalyzing Diels-Alder reactions between cyclopentadiene and acrolein, methacrolein, and crotonalde-hyde, deUvering cycloadducts with enantioselectivities in excess of 94% however, diastereoselectivity is moderate in two cases [124]. 

Diels-Alder reactions of cyclopentadiene with different alkenes proceed at different rates. Cyclopentadiene reacts with acrolein in ether at room temperature (24 h) to give a 95% yield of 27.59 contrasts with the reaction of cyclopentadiene and ethene in ether to give a 74% yield of norbornene (28), but required heating to 200°C in an autoclave at 5800 psi pressure or 32 h. The presence of an electron releasing group on the alkene causes the reaction to proceed with greater difficulty. Vinyl acetate reacted with cyclopentadiene at 190°C in an autoclave (10 h, neat) to give only 25% of 29. 

Compound 78 behaves as an excellent dienophile in the Diels-Alder reaction (Scheme 12). Reaction of 78 with acrolein at 70 °C for 4 days produces the hetero adduct 79 in 52% yield [28]. Treatment with cyclopentadiene at room temperature for 3 days leads to a 96 4 mixture of exo-HQ and endo 81, with an ee of 90% for 80. Considering that the optical purity of 78 is 96%, this translates into a selectivity 95% for the Diels—Alder reaction. Treatment of the mixture with LiAlH4 produces a 96.5 3.5 mixture of exo/endo-hydroxymQthy norbomenQ which, after recrystallization, furnishes pure (1/ , 2i )-2-hydroxybicyclo[2.2.1]hept-5-ene-2-methanol (82). The use of Lewis acid catalysis [TiCl2(0-/5 o-Pr)2] and low temperature ( — 20 °C) in the cycloaddition reaction increases the endo jexo selectivity, but also decreases both the 71-face selectivity and the yield. 

An unexpected and potentially useful mode of reactivity was observed in the reaction of cinnamaldehyde and cyclopentadiene catalysed by diarylprolinol silyl ether 39 [73]. Rather than observing a Diels-Alder adduct, the products resulting from an ene reaction were isolated in excellent yield. The transformation was found to be general for a series of P-aryl acroleins (40) with routinely excellent levels of... 

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. ... 

The complexes are isolated, characterized and used as chiral Lewis acids. Dissociation of the labile ligand liberates a single coordination site at the metal center. These Lewis acids catalyze enantioselective Diels-Alder reactions. For instance, reaction of methacrolein with cyclopentadiene in the presence of the cationic iron complex (L = acrolein) occurs with exo selectivity and an enantiomeric excess of the same order of magnitude as those obtained with the successful boron and copper catalysts (eq 3). ... 

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. 

Diels-Alder reactions of cyclopentadiene and methacrolein with crotonaldehyde are also catalyzed by complexes formed in situ between NbCls or TaCls and bidentate ligands (2 equiv.) such as L-tartrate esters, or a-amino acids (e.g. tryptophan, alanine). Yields with the Ta catalysts are often somewhat better (14-78 %) than with the Nb catalysts. Good exo. endo ratios are obtained but enantioselectivities are still low (7-40 % ee) [185]. Methylrhenium trioxide is an efficient catalyst in these reactions and its best performance is in aqueous solution. Acrolein derivatives and methyl vinyl ketones react with a variety of dienes to give single diastereoisomers in very high yield with as little as 1 % catalyst loading [186]. Examples are shown in Sch. 49. The reaction is sluggish with disubstituted dienophiles and dienes. 

The Diels-Alder reaction between dihydropyran (20) and acrolein gave only a 5% yield of cis 1,8-dioxaoctahydronaphthlene (23) after 15 hours at 150°C. When the reaction was run at 0°C in the presence of a dealuminated Y zeolite, 23 was obtained in 62% yield after 10 minutes (Eqn. 22.17). The Diels-Alder reaction between cyclopentadiene and methyl acrylate took place at 0 C with a... 

It was first reported in 1996 that indium trichloride catalyzes the Diels-Alder reaction in water [131]. The reaction of acrolein with cyclopentadiene in the presence of 20 mol% InCl proceeds stereoselectively (endo. exo=91 9) (Scheme 8.101). Without catalyst the reaction only goes to 60% completion (endo exo=74 26). The InCh-catalyzed Diels-Alder reaction works with either cyclic or non-cyclic dienes. InCh can be recovered for reuse after the reaction is completed. Indium triflate is also an effective catalyst for intramolecular Diels-Alder reactions of furans under microwave irradiation (Scheme 8.102) [132]. 

Chiral secondary amines such as nonracemic imidazolidin-4-ones have been found to be effective asymmetric organocatalysts in the Diels-Alder cyclization of cyclopentadiene and a,p-unsaturated aldehydes [60]. A tyrosine-derived imidazoli-din-4-one was immobilized on PEG to provide a soluble, polymer-supported catalyst 110. In the presence of 110, Diels-Alder cycloaddition of acrolein 112 to 1,3-cyclohexadiene 111 proceeded smoothly to afford the corresponding cycloadduct 113 with high endo selectivity and enantioselectivity up to 92% ee (Scheme 3.31) [61]. 

The Diels-Alder reaction (diene synthesis) is the addition of compounds containing double or triple bonds (dienophiles) to the 1,4 positions of conjugated dienes with the formation of six-membered hydroaromatic rings. Hydrocarbons most often used in the reaction are 1,3-butadiene, cyclopentadiene, and isoprene, and dienophiles used include maleic anhydride, acrolein, and acrylic acid. The literature on this process is thoroughly reviewed by Alder (1), Kloetzel (59), Holmes (48), and Norton (82). 

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