Lewis acid catalysis Diels-Alder reaction

Among the various methods available for the activation of dienes in a Diels-Alder reaction, Lewis acid catalysis is certainly the most important. Our group has reported the first example of a Diels-Alder reaction catalyzed by Bi(0Tf)3xH20 (Scheme 12) [72], which showed high catalytic activity and regioselectivity in comparison to other Sc-, Ti-, Sm-, or Yb-metal-based Lewis acids, well-known for their efficient catalytic activity. Bi(OTf)3 proved to be slightly more endo-selective than Sc(OTf)3. Further, no polymerisation of dienes or dienophiles was observed. Bi(OTf)3 was also found to be superior to SnCI4 and Cu(BF4)2. 

As in the Diels-Alder reaction, Lewis acid catalysis dramatically increases the rates of some ene reactions. Complexation of a Lewis acid to an a, -unsaturated ketone, aldehyde or ester makes the double... 

Generally, the electrocyclic cycloaddition reactions are performed thermally, without catalysis. Diels-Alder reactions are further facilitated by high pressure in hydrophobic structures, suffering hydrophobic collapse within an aqueous environment. Photochemical cycloadditions are often limited by the penetration of the polymeric support by the light of the desired wavelength. However, especially in case of hetero Diels-Alder reactions, Lewis acid catalysis has been applied. On a solid support the use of acid catalysis is often limited by the stability of the support linker, since most common linkers have been designed to be cleavable under acidic conditions. Table 4 shows some of the Lewis acids and the support link used. 

The Diels-Alder reaction of simple a,/3-unsaturated carbonyl compounds generally proceed only under vigorous thermal reaction conditions (150-250°C), " ° even when electron-rich dienophiles are employed. Under vigorous thermal conditions, dimerization and polymerization of the a,jS-unsaturated carbonyl compounds or thermally sensitive electron-rich dienophiles will compete effectively with the desired [4 + 2] cycloaddition. Two experimental methods have been employed to facilitate the 47t participation of simple a,/8-unsaturated carbonyl compounds in Diels-Alder reactions. Lewis acid catalysis has proved effective in accelerating the rate of [4 + 2] cycloadditions of simple a,/3-unsaturated carbonyl compounds with electron-rich olefins [Eqs. (3)-(5)], and it is surprising that this technique has not been... 

What is the effect of micelles on the aqueous Diels-Alder reaction Can micellar catalysis be combined with Lewis-acid catalysis In Chapter 5 these aspects will discussed. 

Corey, E. J. Catalytic Enantioselective Diels-Alder Reactions Methods, Mechanistic Fundamentals, Pathways, and Applications Anptew. Chem. IntEd. 2002, 41, 1560-1567. Fringuelli, F. Piermatti, O. Pizzo, F. Vaccaro, L. Recent Advances in Lewis Acid Catalyzed Diels-Alder Reactions in Aqueous Media Eur. J. Orpj. Chem. 2001, 439-455. Evans, D. A. Johnson, J. S. Diels-Alder Reactions Comprehensive Asymmetric Catalysis 1999, 5, 1177-1235. 

This chapter introduces the experimental work described in the following chapters. Some mechanistic aspects of the Diels-Alder reaction and Lewis-acid catalysis thereof are discussed. This chapter presents a critical survey of the literature on solvent ejfects on Diels-Alder reactions, with particular emphasis on the intriguing properties of water in connection with their effect on rate and selectivity. Similarly, the ejfects of water on Lewis acid - Lewis base interactions are discussed. Finally the aims of this thesis are outlined. 

Lewis-acid catalysis of Diels-Alder reactions... 

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

Unfortunately, the number of mechanistic studies in this field stands in no proportion to its versatility" . Thermodynamic analysis revealed that the beneficial effect of Lewis-acids on the rate of the Diels-Alder reaction can be primarily ascribed to a reduction of the enthalpy of activation ( AAH = 30-50 kJ/mole) leaving the activation entropy essentially unchanged (TAAS = 0-10 kJ/mol)" . Solvent effects on Lewis-acid catalysed Diels-Alder reactions have received very little attention. A change in solvent affects mainly the coordination step rather than the actual Diels-Alder reaction. Donating solvents severely impede catalysis . This observation justifies the widespread use of inert solvents such as dichloromethane and chloroform for synthetic applications of Lewis-acid catalysed Diels-Alder reactions. 

Studies on solvent effects on the endo-exo selectivity of Diels-Alder reactions have revealed the importance of hydrogen bonding interactions besides the already mentioned solvophobic interactions and polarity effects. Further evidence of the significance of the former interactions comes from computer simulations" and the analogy with Lewis-acid catalysis which is known to enhance dramatically the endo-exo selectivity (Section 1.2.4). 

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