Lewis acid catalyzed Diels—Alder reaction effect

In recent years, supramolecular chemistry has produced a number of systems which have been shown to be able to effectively catalyze a Diels-Alder reaction. Most systems selectively afforded only one diastereomer because of a pre-organized orientation of the reactants. These systems include cyclodextrines, of which applications in Diels-Alder chemistry have recently been reviewed89. Some other kinds of non-Lewis acid catalyzed Diels-Alder reactions, including catalysis by proteins and ultrasound, have been discussed by Pindur and colleagues90. 

Singleton, D. A. Merrigan, S. R. Beno, B. R. Houk, K. N. Isotope effects for Lewis acid catalyzed Diels-Alder reactions. The experimental transition state, Tetrahedron Lett. 1999, 40, 5817-5821. 

Theoretical calculations have also permitted one to understand the simultaneous increase of reactivity and selectivity in Lewis acid catalyzed Diels-Alder reactions . This has been traditionally interpreted by frontier orbital considerations through the destabilization of the dienophile s LUMO and the increase in the asymmetry of molecular orbital coefficients produced by the catalyst. Birney and Houk have correctly reproduced, at the RHF/3-21G level, the lowering of the energy barrier and the increase in the endo selectivity for the reaction between acrolein and butadiene catalyzed by BH3. They have shown that the catalytic effect leads to a more asynchronous mechanism, in which the transition state stmcture presents a large zwitterionic character. Similar results have been recently obtained, at several ab initio levels, for the reaction between sulfur dioxide and isoprene. ... 

Diels-Alder reactions constitute one of the most important methodologies for the constructuction of a cyclic molecular framework. Lanthanide Lewis acid catalyzed Diels-Alder reaction was pioneered by Danishefsky et al., who revealed that NMR shift reagent Eu(hfc)3 served as chiral catalyst in hetero Diels-Alder reaction of silyloxydiene and aldehydes [32]. Later, although Yb(OTf)3 was first introduced for Diels-Alder reactions as an effective catalyst among lanthanide triflates, scandium triflates (Sc(OTf)3), classified as rare earth metal triflate, has gained popularity as a superior catalyst for Diels-Alder reactions [11, 33]. This section highlights several examples of the reactions where lanthanide triflates displayed preferable performance over scandium triflates. 

The first reported use of In(III) salts as a catalyst in cycloaddition reactions was in the Diels-Alder reaction carried out in water. Loh et al. found that InCls has the same effects as most Lewis acids in the Diels-Alder reaction, that is, enhancements of facial select vities and reaction rates [172] (Figure 8.73). Reactions of various combinations of dienes (cyclic and noncyclic) and dienophiles were reported to give high facial selectivities and excellent yields. The ab initio calculations done by Yamabe et al for the Lewis acid catalyzed Diels-Alder reaction showed that InCh catalyzed reaction had similar geometries to that of AICI3 catalyzed reactions [173]. 

The Lewis acid-catalyzed Diels-Alder reactions have been studied in depth, particularly when a,P-unsaturated aldehydes and ketones are involved as dienophiles. It has been established that the effect of the catalyst is to lower the LUMO energy of the dienophile, by coordination with the carbonyl group. It is evident that the more stable eomplex will cause a larger lowering in the LUMO energy. In this case, in the presence of the Lewis acid, complexes 21 and 22 should be formed. However, as we have discussed above, the coordination ability of more electrophilic carbonyl groups to a Lewis acid is weaker than that of their less electrophilic analogues. In fact, we have commented previously that trifluoroaceto-phenone-BFs complex 17 has not been detected by NMR. Consequently, it is reasonable to consider that in the presence of a Lewis acid only 22 is formed in flic reaction medium (Scheme 3.11). 

Enantioselective imidation of alkyl aryl sulfides with A -alkoxycarbonyl azides as a nitrene precursor is effected by using (OC)Ru(salen) complex as catalyst. The steric and electronic nature of the Af-alkoxycarbonyl group strongly affect the enantioselectivity and the reaction rate. In a systematic and well-executed study of ligand effects on Lewis-acid-catalyzed Diels-Alder reaction, it has been shown that the attachment of aromatic a-amino acid ligands to copper(II) ions leads to an increase in the overall rate of the Diels-Alder reaction between 3-phenyl-l-(2-pyridyl)-2-propene-l-one (Din) and cyclopentadiene... 

Lewis acids have been widely used to catalyze Diels-Alder reactions when thermal conditions were not efficient [43]. A limitation of the Lewis acid catalyzed Diels-Alder cycloaddition reaction has often been found to be due to the sensitivity of the substrates to the strongly acidic media. For instance, when considering the addition of phenylacetylene derivatives to 1-silyloxypyrrole, it was found that the Lewis acids (AICI3, BF3, TiCU) led to decomposition of starting materials, while the thermal processes afforded only negligible amounts of the desired cycloadduct [44]. The successful preparation of the cycloadduct product was achieved with lithium perchlorate in ether. This approach did not produce a very acidic reaction medium, but considerably lowered the LUMO pyrrole energy, almost as much as protonation by itself (Table 14). The final effect was that the reaction became a strongly LUMO diene controlled Diels-Alder reaction. 

Lewis acids such as zinc chloride, boron trifluoride, tin tetrachloride, aluminum chloride, methylaluminum dichloride, and diethylaluminum chloride catalyze Diels-Alder reactions.22 The catalytic effect is the result of coordination of the Lewis acid with the dienophile. The complexed dienophile is more electrophilic and more reactive toward electron-rich dienes. The mechanism of the addition is believed to be concerted and enhanced regio- and stereoselectivity is often observed.23... 

Kobayashi has found that scandium triflate, Sc(OTf)3,36 and lanthanide triflate, Ln(OTf)3, are stable and can be used as Lewis catalysts under aqueous conditions. Many other Lewis acids have also been reported to catalyze Diels-Alder reactions in aqueous media. For example, Engberts reported37 that the cyclization reaction in Eq. 12.7 in an aqueous solution containing 0.010 M Cu(N03)2 is 250,000 times faster than that in acetonitrile and about 1,000 times faster than that in water alone. Other salts, such as Co2+, Ni2+, and Zn2+, also catalyze the reaction, but not as effectively as Cu2+. However, water has no effect on the endo-exo selectivity for the Lewis-acid catalyzed reaction. 

It has been found that the combination of Lewis acids and surfactants is particularly effective for catalyzing Diels-Alder reactions in water. The effect of micelles of SDS, CTAB, dodecyl heptaoxyethy-lene ether (Q2E7), and copper and zinc didodecyl sulfate [M(DSb] on the Diels-Alder reaction of 3-(p-substituted phenyl)- l-(2-pyridyl)-2-propen-l-ones (Figure 12.1) with cyclopentadiene was studied. 

One of the most effective approaches to implementing the Diels-Alder participation of 1-oxa-1,3-butadienes is through the use of an intramolecular [4 + 2] cycloaddition reaction.A select set of thermal and Lewis acid-catalyzed intramolecular cycloaddition reactions of unactivated and electron-rich alkenes with a,P-unsaturated aldehydes and ketones has been detailed. Two examples of the poorly matched intramolecular Diels-Alder reaction of an a,P-unsaturated aldehyde (4 ir component) with an a, 3-unsaturated amide (2ir component) have proven successful (190-160 °C) and may be attributed to the entropic assistance provided by the intramolecular reaction. These observations have been applied in... 

EtAlCk.catalyzed Diels-Alder reactions between alkyl-substituted 1,3-butadienes and (r -acrylol) (r -cyclopentadienyl) diacarbonyliron(II) complexes have been found, where the observed regio- and stereochemistry were consistent with that generally observed in Diels-Alder reactions [55]. Conventional Lewis acids such as BF -OEt. and TiCl4 were not effective in promoting the desired cycloaddition. 

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... 

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]. 

Clay treated with transition metals, Fe and Cr were especially effective, has been found to catalyze Diels-Alder reactions and pyrrole was among the dienes which was examined. Using the Cr catalyst, pyrrole gave a 4 1 mixture of exo and endo adducts with methyl vinyl ketone. f94JCS(Pl)761>The relative effectiveness of the various metals examined does not appear to correlate with either Lewis acidity or redox potential. A tentative suggestion is that the metal cations may facilitate reaction through coordination complexes. 

Lewis acids such as zinc chloride, aluminum chloride, and diethylaluminum chloride catalyze Diels-Alder reactions. The catalytic effect is the result of coordination of the Lewis acid with the dienophile. 

To overcome these problems with the first generation Brmsted acid-assisted chiral Lewis acid 7, Yamamoto and coworkers developed in 1996 a second-generation catalyst 8 containing the 3,5-bis-(trifluoromethyl)phenylboronic acid moiety [10b,d] (Scheme 1.15, 1.16, Table 1.4, 1.5). The catalyst was prepared from a chiral triol containing a chiral binaphthol moiety and 3,5-bis-(trifluoromethyl)phenylboronic acid, with removal of water. This is a practical Diels-Alder catalyst, effective in catalyzing the reaction not only of a-substituted a,/ -unsaturated aldehydes, but also of a-unsubstituted a,/ -unsaturated aldehydes. In each reaction, the adducts were formed in high yields and with excellent enantioselectivity. It also promotes the reaction with less reactive dienophiles such as crotonaldehyde. Less reactive dienes such as isoprene and cyclohexadiene can, moreover, also be successfully employed in reactions with bromoacrolein, methacrolein, and acrolein dienophiles. The chiral ligand was readily recovered (>90%). 

A great advantage of catalyst 24b compared with other chiral Lewis acids is that it tolerates the presence of ester, amine, and thioether functionalities. Dienes substituted at the 1-position by alkyl, aryl, oxygen, nitrogen, or sulfur all participate effectively in the present asymmetric Diels-Alder reaction, giving adducts in over 90% ee. The reaction of l-acetoxy-3-methylbutadiene and acryloyloxazolidinone catalyzed by copper reagent 24b, affords the cycloadduct in 98% ee. The first total synthesis of ewt-J -tetrahydrocannabinol was achieved using the functionalized cycloadduct obtained [23, 33e] (Scheme 1.39). 

To achieve catalytic enantioselective aza Diels-Alder reactions, choice of metal is very important. It has been shown that lanthanide triflates are excellent catalysts for achiral aza Diels-Alder reactions [5]. Although stoichiometric amounts of Lewis acids are often required, a small amount of the triflate effectively catalyzes the reactions. On the basis of these findings chiral lanthanides were used in catalytic asymmetric aza Diels-Alder reactions. The chiral lanthanide Lewis acids were first developed to realize highly enantioselective Diels-Alder reactions of 2-oxazolidin-l-one with dienes [6]. 

The coupling photolysis Lewis acid is also sometimes effective in promoting a Diels-Alder reaction. Thus, cationic (R,S)-(ON)Ru-salen homochiral complex 71 catalyzed the Diels-Alder reaction between Danishefsky s diene and benzaldehyde when the reagents were exposed to direct sunlight through a window or to incandescent light in t-butyl methyl ether (TBME)[49] (Equation 4.8). The reaction in the dark was very slow and only 3 % ee was detected. 

Jorgensen et al. [84] studied how solvent effects could influence the course of Diels-Alder reactions catalyzed by copper(II)-bisoxazoline. They assumed that the use of polar solvents (generally nitroalkanes) improved the activity and selectivity of the cationic copper-Lewis acid used in the hetero Diels-Alder reaction of alkylglyoxylates with dienes (Scheme 31, reaction 1). The explanation, close to that given by Evans regarding the crucial role of the counterion, is a stabilization of the dissociated ion, leading to a more defined complex conformation. They also used this reaction for the synthesis of a precursor for highly valuable sesquiterpene lactones with an enantiomeric excess superior to 99%. 

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