Bidentate dienophiles, Diels-Alder

Consequently, in initial attempts to extend the scope, we aimed to identify catalysis of Diels-Alder reactions of other bidentate dienophiles in water. This task turned out to be more difficult than expected Scheme 4.5 provides a collection of potentially chelating dienophiles that all failed to... 

Careful examination of literature reporting Lewis-acid catalysis of Diels-Alder reactions in combination with kinetic investigations indicate that bidentate (or multidentate) reactants are required in order to ensure efficient catalysis in water. Moreover, studies of a number of model dienophiles revealed that a potentially chelating character is not a guarantee for coordination and subsequent catalysis. Consequently extension of the scope in this direction does not seem feasible. 

Different results were obtained by Kobayashi and colleagues [76] performing the Diels-Alder reaction of 2,3-dimethyl butadiene with N-butylmaleimide in water in the presence of various dodecyl sulfate (DS) and dodecane sulfonate (DCS) LASCs [M(DS) M = Sc, Cu n = 3, 2 M(DCS) M = Sc, Yb, Mn, Co, Cu, Zn, Na, Ag n = 3,2, 1]. Unexpectedly, no acceleration was observed with respect to the reactions carried out in water only, and no catalytic effect was found also by using a bidentate dienophile which, in principle, should be able to coordinate the metal cation in the LASC system. 

In stereoselective reactions, Zn11 Lewis acids work well to achieve high selectivities (Scheme 54). Chiral complexes of Zn11 with chiral bis(oxazoline) ligands act as effective catalysts in Diels-Alder reactions of reactive dienes with dienophiles having bidentate chelating moieties such as... 

Carbohydrates have found widespread use as chiral auxiliaries in asymmetric Diels-Al-der reactions156. A recent example is a study conducted by Ferreira and colleagues157 who used carbohydrate based chiral auxiliaries in the Lewis acid catalyzed Diels-Alder reactions of their acrylate esters 235 with cyclopentadiene (equation 66). Some representative results of their findings, including the ratios of products 236 and 237, have been summarized in Table 9. The formation of 236 as the main product when diethylaluminum chloride was used in dichloromethane (entry 3) was considered to be the result of an equilibrium between a bidentate and monodentate catalyst-dienophile complex. The bidentate complex would, upon attack by the diene, lead to 236, whereas the monodentate complex would afford 236 and 237 in approximately equal amounts. The reversal of selectivity on changing the solvent from dichloromethane to toluene (entry 2 vs 3) remained unexplained by the authors. 

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. 

Considering that the activity of a Lewis acid depends strongly on the stability of the acid-base complex and that the complexation is notoriously hampered by chemically hard solvents like water, it is clear that reactions of bidentate dienophiles can be catalysed very efficiently36. Prototypical are the derivatives of 3-phenyl-l-(2-pyridyl)-2-propen-l-ones (vide infra). Their Diels-Alder reactions (Table 24) clearly show that the accelerating solvent effect of water is still present in the Lewis acid catalysed reactions, and that the Lewis acid activity is not necessarily hindered by the solvent301. While... 

Lewis-acid catalysis of Diels-Alder reactions involving bidentate dienophiles in water is possible also if the beneficial effect of water on the catalyzed reaction is reduced relative to pure water. There are no additional effects on endo-exo selectivity. As expected, catalysis by Cu ions is much more efficient than specific-acid catalysis.Using a-amino acids as chiral ligands, Lewis-acid enan-tioselectivity is enhanced in water compared to organic solvents. Micelles, in the absence of Lewis acids, are poor catalysts, but combining Lewis-acid catalysis and micellar catalysis leads to a rate accelaration that is enzyme-like. 

Engberts and co-workers (Otto et al., 1996) reported a detailed study of a Diels-Alder reaction that was catalyzed by Lewis acids in water. They presented the results of the effects of Co Ni, Cu and Zn ions as Lewis acid catalysts on the rate and endo-exo selectivity of the DA reaction between the bidentate dienophiles 3-phenyl-l-(2-pyridyl)-2-propen-l-ones and cyclopentadiene in water (see fig. 6.6). Relative to the uncatalyzed reaction in acetonitrile, catalysis by 0.010 M Cu(N03)2 in water accelerates the Diels-Alder reaction by a factor of 79,300. Water does not induce an enhanced endo-selectivity for this reaction. 

The domino carbonylation and Diels-Alder reaction proceed only as an intramolecular version. Attempted carbonylation and intermolecular Diels-Alder reaction of conjugated 2-yne-4-enyl carbonates 101 in the presence of various alkenes as dienophiles give entirely different carbocyclization products without undergoing the intermolecular Diels-Alder reaction. The 5-alkylidene-2-cyclopenten-4-onecarboxy-lates 102 were obtained unexpectedly by the incorporation of two molecules of CO in 82% yield from 101 at 50 °C under 1 atm [25], The use of bidentate ligands such as DPPP or DPPE is important. The following mechanism of the carbocyclization of 103 has been proposed. The formation of palladacyclopentene 105 from 104 (oxidative cyclization) is proposed as an intermediate of 108. Then CO insertion to the palladacycle 105 generates acylpalladium 106. Subsequent reductive elimination affords the cyclopentenone 107, which isomerizes to the cyclopentenone 108 as the final product. 

An important challenge in the asymmetric catalytic Diels-Alder reaction is the use of simple ketone dienophiles to obtain high enantioselectivity. Indeed, the success of chiral Lewis acid-mediated Diels-Alder reactions is founded upon the use of dienophiles such as aldehydes, esters, quinones [36-43], and bidentate chelating carbonyls [44-47], where high levels of lone pair discrimination are achieved in the metal association step, an organizational event that is essential for enantiocontrol. In contrast, Lewis acid coordination to ketone dienophiles is generally non-selective, since the participating lone pairs are positioned in similar steric and electronic environments (Eq. 4). The ability for diastereomeric activa-... 

Much has been published on Lewis acid-catalyzed Diels-Alder reactions between the bidentate dienophile 3-acryloyl-l,3-oxazolidin-2-one and the prototypical diene component cyclopentadiene these afford the endo cycloaddition product with good selectivity. This reaction has become the prototype for two-point binding, Lewis acid catalyzed, asymmetric Diels-Alder reactions. For easier comparison, the data in Sch. 41 include. 

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. 

Davies and coworkers , for example, used iV-enoyl derivatives of a cw-l-aminoindan-2-ol based L3-oxazolidin-2-one (222) as chiral dienophiles in the Diels-Alder reactions with isoprene (91a) and piperylene (91b) which give 223 (equation 62). Their results have been summarized in Table 6. The reactions proceeded with high endo/exo and regioselectivities. Bidentate co-ordination of the catalyst to both carbonyl groups kept the dienophile in a rigid conformation, which gave rise to the high de values observed. 

As for surfactants, they have uncertain, sometimes contradictory, consequences on reaction rates [45], but the main advantage of using surfactants as additives lies in their solubilizing effect. Special attention has been paid to the rate-accelerating effect of Lewis acid catalysts. The first study deals with the Diels-Alder reaction between cyclopentadiene and a bidentate dienophile a large acceleration can be achieved by the combined use of copper(II) nitrate as catalyst and water as solvent. The rate enhancement imposed on the catalyzed Diels-Alder reaction is much less pronounced than that for the uncatalyzed reaction... 

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