Lewis-acid catalysis of Diels-Alder reactions

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. 

What is the scope of Lewis-acid catalysis of Diels-Alder reactions in water An approach of extending the scope by making use of a temporary secondary coordination site is described in Chapter 4. 

In summary, the effects of a number of important parameters on the catalysed reaction between 2.4 and 2.5 have been examined, representing the first detailed study of Lewis-acid catalysis of a Diels-Alder reaction in water. Crucial for the success of Lewis-acid catalysis of this reaction is the bidentate character of 2.4. In Chapter 4 attempts to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water beyond the restriction to bidentate substrates will be presented. 

The merits of (enantioselective) Lewis-acid catalysis of Diels-Alder reactions in aqueous solution have been highlighted in Chapters 2 and 3. Both chapters focused on the Diels-Alder reaction of substituted 3-phenyl-1-(2-pyr idyl)-2-prop ene-1-one dienophiles. In this chapter the scope of Lewis-acid catalysis of Diels-Alder reactions in water is investigated. Some literature claims in this area are critically examined and requirements for ejfective Lewis-acid catalysis are formulated. Finally an attempt is made to extend the scope of Lewis-acid catalysis in water by making use of a strongly coordinating auxiliary. 

In a second attempt to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water, we have used the Mannich reaction to convert a ketone-activated monodentate dienophile into a potentially chelating p-amino ketone. The Mannich reaction seemed ideally suited for the purpose of introducing a second coordination site on a temporary basis. This reaction adds a strongly Lewis-basic amino functionality on a position p to the ketone. Moreover, the Mannich reaction is usually a reversible process, which should allow removal of the auxiliary after the reaction. Furthermore, the reaction is compatible with the use of an aqueous medium. Some Mannich reactions have even been reported to benefit from the use of water ". Finally, Lewis-acid catalysis of Mannich-type reactions in mixtures of organic solvents and water has been reported ". Hence, if both addition of the auxiliary and the subsequent Diels-Alder reaction benefit from Lewis-acid catalysis, the possibility arises of merging these steps into a one-pot procedure. 

As anticipated from the complexation experiments, reaction of 4.42 with cyclopentadiene in the presence of copper(II)nitrate or ytterbium triflate was extremely slow and comparable to the rate of the reaction in the absence of Lewis-acid catalyst. Apparently, Lewis-acid catalysis of Diels-Alder reactions of p-amino ketone dienophiles is not practicable. 

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. 

Regioselectivities [7] and endo selectivity [8, 9] increase upon Lewis acid catalysis of Diels-Alder reactions (Scheme 9). Houk and Strozier [10] found that protonation on the carbonyl oxygen of acrolein amplifies the LUMO at the terminal and... 

Lewis-acid catalysis of Diels-Alder reactions (Figure 7.5) in organic solvents leads to an enhancement of the reaction rate, because of the lowering in energy for the lowest unoccupied molecular orbital (LUMO) of the dienophile, and an improvement in the selectivity with specific ligands. 

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. 

The more or less accidental discovery that fluorinated y9-diketonates of europium both effect the Lewis acid catalysis of Diels-Alder reactions [10] and interact with carbonyl functionalities of the substrates [102] emerged in a very prolific research. Despite the ready feasibility of homo-Diels-Alder reactions [103], hetero-Diels-Alder cycloadditions are preferentially mediated [104]. The endo select vities... 

Lewis-Acid Catalysis of Diels-Alder Reactions.161... 

Lewis-acid catalysis of Diels-Alder reactions is now commonplace but the use of iron(O) to catalyse the addition of butadiene to an ynamine is worthy of note [e.g. (132) -> (133)]. Also somewhat unusual is the asymmetric induction observed when chiral dichloroaluminium alkoxides such as (134) are used as catalysts. Finally a cautionary note in one case the presence of the stannic chloride catalyst brings about the rearrangement of the initial adduct (135) into (136). °°... 

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