Lewis acid catalyzed Diels—Alder reaction rate enhancement

Clifford and Rayner have reported enhanced selectivities for Lewis acid catalyzed Diels-Alder cycloadditions in sc C02 relative to organic solvents. It is well known that Lewis acids catalyze Diels-Alder reactions and can improve their rate and selectivity (Dell, 1998 Santelli, 1996). The endo exo product selectivity for the Sc(Otf)3-catalyzed reaction between cyclopenta-diene and alkyl acrylates (eq. 2.3) could be optimized to 24 1 by controlling the density of sc C02 (Clifford et al., 1997, 1998 Oakes et al., 1999), whereas in toluene the endo exo ratio was 10 1. 

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]. 

Although cycloadditions and rearrangements often proceed without catalysts, the selectivity of the reaction and the reactivity of very reluctant molecules can be enhanced by a Lewis acid. The Diels-Alder reaction can be performed at enhanced reaction rate in ionic liquids with the addition of ZnCl2 (eq. (4)) [42]. The Claisen rearrangement was also reported to be superior if catalyzed by Sc(OTf)3 in ionic liquids [43]. 

The combination of Lewis-acid catalysis and sc-COi has also been investigated. One of these studies involved the AlCls-catalyzed Diels Alder reaction of isoprene and maleic anhydride in sc-COi at 67 °C and at 74.5-78.5 bar [89]. The reaction rate was enhanced with respect to the uncatalyzed reaction and an unconcerted two-step mechanism was suggested [89]. 

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... 

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. 

Bi(0Tf)3xH20 has been found to catalyze carbonyl-Diels-Alder reactions in water involving glyoxylic acid as the dienophile (Scheme 14) [72]. In contrast to other Lewis acids (such as Sn(OTf)2, Yb(OTf)3, Nd(OTf)3, Ce(OTf)3 and Sc(OTf)3), the strong catalytic power of Bi(0Tf)3-xH20 made it necessary to reduce its amount as well as the reaction temperature. Bi(0Tf)3-xH20 enhanced the reaction rate but with some dienes the reaction led to competitive formation of the ene reaction product. 

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. 

Since the seminal contributions in the 1980s of Breslow [la] for the Diels-Alder reaction and Kuntz and Ruhrchemie for hydroformylation reactions [lb], there has been an upsurge in interest in using water as the solvent, not only to enhance the reaction rates, but also to perform organic reactions that would otherwise be impossible, or to elicit new selectivities. Several reviews have been devoted specially to such a use [2], which nevertheless does not exclude the possibility of further catalyzing the reactions with Lewis acids [3] or the use of Lewis acid-surfactant-combined catalysis (LASC) [4],... 

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