2- Methacrolein, Diels-Alder reactions with

Diels-Alder Reaction. The Diels-Alder reaction of methacrolein with 1,3-dienol derivatives can also be catalyzed by the chiral BINOL-derived titanium complex BINOL-T1CI2. The endo adduct was obtained in high enantioselectivity (eq 15). The sense of asymmetric induction is exactly the same as observed for the asymmetric catalytic reactions shown above. Asymmetric catalytic Diels-Alder reactions with naphthoquinone derivatives as a dienophile provide an efficient entry to the asymmetric synthesis of anthracyclinone aglycones (eq 16). ... 

Aminosiloxy dienes have been found to exhibit unusually high reactivity in Diels-Alder reactions with a wide range of electron-deficient dienophiles.2 5 Determination of the second order rate constants with methacrolein showed the parent aminosiloxy diene to be about 103 more reactive than the analogous 1-alkoxy-3-siloxy diene.4 The reactions of aminosiloxy dienes with various dienophiles occur under mild conditions and afford the corresponding cycloadducts in high yields and with complete regioselectivity. An extensive study on the preparation and cycloadditions of amino siloxy dienes has been carried out.3... 

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. 

In 2002, Strukul et al. [18] reported the synthesis of a series of Pd(II) and Pt(II) cationic complexes of the types [(P-P)M-(solv)](Y)2, [(P-P)M(h2-Y)](Y), and [(P-P)M(m-Cl)]2(Y)2 (P-P = various diphosphines including chiral diphosphines M = Pd, Pt Y = TfO , Cl04, Bp4 ) (Figure 16.2). The variety of cationic complexes of Pd(II) (57) and Pt(II) (58) were found to be active catalysts for the Diels-Alder reaction between cyclopentadiene or cyclohexadiene and a number of simple dienophiles such as acrolein, methacrolein, and methylvinyl ketone. Some of the complexes modified with chiral diphosphines promoted enantioselective Diels-Alder reaction with moderate enatiomeric excesses up to 49% ee. 

Evans s bis(oxazolinyl)pyridine (pybox) complex 17, which is effective for the Diels-Alder reaction of a-bromoacrolein and methacrolein (Section 2.1), is also a suitable catalyst for the Diels-Alder reaction of acrylate dienophiles [23] (Scheme 1.33). In the presence of 5 mol% of the Cu((l )-pybox)(SbF5)2 catalyst with a benzyl substituent, tert-butyl acrylate reacts with cyclopentadiene to give the adduct in good optical purity (92% ee). Methyl acrylate and phenyl acrylate underwent cycloadditions with lower selectivities. 

Oxazoborolidinone 8 is an example of catalyst supported on silica gel. It is prepared by immobilizing the N-tosyl-0-allyl-(S)-tyrosine with mercaptopropyl silica and treatment with BF3 and has been used to catalyze the Diels-Alder reaction of methacrolein with cyclopentadiene [17] (Equation 4.2). The cycloaddition occurs with good diastereoselectivity but with low enantioselec-tivity. 

Ruthenium complexes have also been reported as active species for enan-tioselective Diels-Alder reactions. Faller et al. prepared a catalyst by treatment of (-)-[( ] -cymene)RuCl(L)]SbF6 with AgSbFe resulting in the formation of a dication by chloride abstraction [95]. The ligand was (-l-)-IndaBOx 69 (Scheme 36) and the corresponding complex allowed the condensation of methacrolein with cyclopentadiene in 95% conversion and 91% ee. As another example, Davies [96] prepared the complex [Ru(Fl20)L ( i -mes)] [SbFe]2 (with 70 as L in Scheme 36), and tested its activity in the same reaction leading to the expected product with similar activity and lower enan-tioselectivity (70%). 

Zeijden [112] used chiral M-functionalized cyclopentadiene ligands to prepare a series of transition metal complexes. The zirconium derivative (82 in Scheme 46), as a moderate Lewis acid, catalyzed the Diels-Alder reaction between methacroleine and cyclopentadiene, with 72% de but no measurable enantiomeric excess. Nakagawa [113] reported l,T-(2,2 -bis-acylamino)binaphthalene (83 in Scheme 46) to be effective in the ytterbium-catalyzed asymmetric Diels-Alder reaction between cyclopentadiene and crotonyl-l,3-oxazolidin-2-one. The adduct was obtained with high yield and enantioselectivity (97% yield, endo/exo = 91/9, > 98% ee for the endo adduct). The addition of diisopropylethylamine was necessary to afford high enantioselectivities, since without this additive, the product was essentially... 

A chiral NHC-Ru complex 158 was used in the Diels-Alder reaction between methacrolein 156 and cyclopentadiene 157 (Scheme 5.41) [47]. The adduct 159 was obtained in an excellent yield under mild conditions, albeit with low enantioselectivity. 

Similar reactions were applied to the syntheses of rf/-ep/-pyroangolen-solide, i/-pyroangoensolide (Eq. 12.29)88 and the formal synthesis of the Inhoffen-Lythgoe diol (Eq. 12.30).89 The key step in the formal synthesis of the Inhoffen-Lythgoe diol is the aqueous Diels-Alder reaction between the sodium salt of the diene and methacrolein to form the cycloadduct, which then undergoes subsequent reactions to form the known hydrin-dan. Sodium (E)-4, 6, 7-octatrienoate reacted smoothly with a variety of dienophiles to give conjugated diene products.90... 

Figure 39 The enantioselective polymer-supported catalysts (61) of chiral oxazaborolidinone with cross-linking structures for use in the Diels-Alder reaction of methacrolein with cyclopentadiene. (Adapted from ref. 85.)...

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

Chiral rhodium284 and ruthenium catalysts285,286 have been reported to catalyze the Diels-Alder reaction of methacrolein with cyclopentadiene. Several bis(oxazolidine) and 2-pyridyl-l,3-oxazolidine ligands were used as chiral ligands. The adducts were obtained with only moderate enantioselectivities. 

The chiral dialuminum Lewis acid 14, which is effective as an asymmetric Diels-Alder catalyst, has been prepared from DIBAH and BINOL derivatives (Scheme 12.12). " The catalytic activity of 14 is significantly greater than that of monoaluminum reagents. The catalyst achieves high reactivity and selectivity by an intramolecular interaction of two aluminum Lewis acids. Similarly, the chiral trialuminum Lewis acid 15 is quantitatively formed from optically pure 3-(2,4,6-triisopropylphenyl)binaphthol (2 equiv) and MeaAl (3 equiv) in CH2CI2 at room temperature (Scheme 12.12). " The novel structure of 15 has been ascertained by NMR spectroscopic analysis and measurement of the methane gas evolved. Trinuclear aluminum catalyst 15 is effective for the Diels-Alder reaction of methacrolein with cyclopentadiene. Diels-Alder adducts have been obtained in 99% yield with 92% exo selectivity. Under optimum reaction conditions, the... 

A chiral dinuclear Ti(IV) Lewis acid catalyst 18 can be prepared in situ from a 1 2 molar mixture of (7 )-3,3 -di(2-mesitylethynyl)binaphthol and Ti(Oi-Pr)4 at ambient temperature. The 3- and 3 -substituents on the chiral ligand are effective for preventing undesired aggregation between Ti(IV) complexes and increasing the enantioselectivity (up to 82% ee) in the Diels-Alder reaction of methacrolein with cyclopentadiene (Scheme 12.16). ... 

Cationic chiral Rh and Ru complexes were prepared by reaction of [(T -C5H5)RhCl2]2 and [RuCl2(T 6-mes)]2 with chiral bidentate or monodentate oxazoline ligands, respectively. Treatment of these monocationic metal complexes, with AgSbF produced dicationic complexes, which were also found to be highly effective for the enantioselective Diels-Alder reaction of methacrolein [12,13] (Eq. 8A.6). On the basis of spectroscopic and structural studies, a full catalytic cycle of a chiral Ru complex was proposed for the Diels-Alder reaction of cyclopen-tadiene with methacrolein [14]. 

The moderate Lewis acidity of ruthenium complexes was used to promote catalytic Diels-Alder reaction of dienes and acrolein derivatives [21-23]. The enantioselective Diels-Alder reaction of methacrolein with dienes was catalyzed with cationic ruthenium complexes containing an arene or cyclo-pentadienyl (Cp) ligand and a chiral ligand such as phosphinooxazoline, pyridyl-oxazoline, monoxidized 2,2 -bis(diphenylphosphino)-1, T-binaphthyl (BINPO)or l,2-bis[bis(pentafluorophenyl)phosphanyloxy]-l,2-diphenylethane (BIPHOP-F). The reaction gave the cycloadduct in high yields with excellent... 

These complexes are the first examples of multifunctional catalysts and demonstrate impressively the opportunities that can reside with the as yet hardly investigated bimetallic catalysis. The concept described here is not limited to lanthanides but has been further extended to main group metals such as gallium [31] or aluminum [32]. In addition, this work should be an incentive for the investigation of other metal-binaphthyl complexes to find out whether polynuclear species play a role in catalytic processes there as well. For example, the preparation of ti-tanium-BINOL complexes takes place in the presence of alkali metals [molecular sieve ( )]. A leading contribution in this direction has been made by Kaufmann et al, as early as 1990 [33], It was proven that the reaction of (5)-la with monobromoborane dimethyl sulfide leads exclusively to a binuclear, propeller-like borate compound. This compound was found to catalyze the Diels-Alder reaction of cyclopentadiene and methacrolein with excellent exo-stereoselectivity and enantioselectivity in accordance with the empirical rule for carbonyl compounds which has been presented earlier. 

Asymmetric Diels-Alder Reaction. Although the asymmetric Diels-Alder reaction of cyclopentadiene with methacrolein... 

Asymmetric Diels-Alder Reaction of Unsaturated Aldehydes . The boron atom of acyloxyborane is activated by the electron-withdrawing acyloxy groups, and consequently acyloxyborane derivatives are sufficiently Lewis acidic to catalyze certain reactions. Thus, asymmetric Diels-Alder reactions of a,p-enals with dienes using (1) as a Lewis acid catalyst have been developed. For example, the reaction of cyclopentadiene and methacrolein gives the adduct in 85% yield (endo exo= 11 89) and 96% ee (major exo isomer) (eq 3). Some additional examples are listed in Figure 1. The a-substituent on the dienophile increases the enantioselectivity, while p-substitution dramatically decreases the selectivity. In the case of a substrate having substituents in both a- and p-positions, high enantioselectivity is observed thus the a-substituent effect overcomes that of the p-substituent. 

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). ... 

Since the disclosures that the thermal dimerizations of acrolein and methyl vinyl ketone provide the 3,4-dihydro-2//-pyrans (1, 2) derived from 4ir and 2Tt participation of the a,3-unsaturated carbonyl compound in a Diels-Alder reaction, an extensive series of related observations have been detailed. This work has been the subject of several comprehensive reviews - - including the Desimoni and Tacco-ni extensive tabular compilation of work through 1974. Consequently, the prior reviews should be consulted for thorough treatments of the mechanism, scope, and applications of the [4 + 2] cycloaddition reactions of a,3-unsaturated carbonyl compounds. The [4 + 2] cycloaddition reactions of 1-oxa-1,3-butadienes with their 4-it participation in the Diels-Alder reaction exhibit predictable regioselectivity with the preferential or exclusive formation of 2-substituted 3,4-dihydro-2W-pyrans (equation 1). The exceptions to the predicted regioselectivity that have been observed involve the poorly matched [4 + 2] cycloaddition reaction of an electron-deficient l-oxa-l,3-butadiene with an electron-deficient dienophile, e.g. methyl crotonate or methacrolein. - Rigorous or simplified theoretical treatments of the [4 + 2] cycloaddition reaction of 1-oxa-1,3-butadienes predict the preferential formation of 2-substituted 3,4-dihy-dro-2f/-pyrans and accommodate the preferred endo approach of the reactants in which the carbon-carbon bond formation is more advanced than carbon-oxygen bond formation, i.e. a concerted but nonsynchronous [4 + 2] cycloaddition reaction. ... 

Bao and Wulff compared catalysts prepared from vaulted biaryls and from bromo-borane dimethylsulfide with those generated from linear biaryls with regard to their capacity to provide enantioselective induction in the Diels-Alder reaction of cyclo-pentadiene and methacrolein (Eqs 6 and 7) [7]. Because the (5) enantiomers of vaulted biaryls result in induction opposite to that resulting from use of the (5) enantiomer of binaphthol, and because effective catalysts cannot be generated from binaphthol and phenylboron dichloride, suggest that the catalysts obtained from vaulted biaryls do not have the same structure as the Cs-symmetrical catalyst produced from binaphthol. 

We have also studied the solution conformations of CAB-complexed methacrolein and crotonaldehyde by use of NOE measurements (Table 1) [12]. These results are in agreement with the transition-state preference for the s-trans or s-cis conformation of a,/8-enals, on the basis of the enantioselectivity of the aldol and Diels-Alder reactions catalyzed by CAB. Finally, it has been established that the effective shielding of the si face of the CAB-coordinated a, -enal arises from /r-stacking of the 2,6-diisopropoxy-benzene ring and the coordinated aldehyde. 

Itsuno et al. explored the possibility of using polymer-supported chiral Lewis acids in a model Diels-Alder reaction of methacrolein with cyclopentadiene [23a]. By using an insoluble polymer-supported Lewis acid [23], prepared from borane with cross-linked polymers with a chiral moiety such as an A-sulfonylamino acid, the Diels-Alder adduct is obtained in good yield with almost perfect exo selectivity and moderate enantioselectivity (Eq. 23). 

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 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. 

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