Dienophiles, also

D-A rxns with electron deficient dienes and electron rich dienophiles also work well. These are refered to as reverse demand D-A rxns. 

Furan and maleic anhydride undergo the Diels-Alder reaction to form the tricycHc 1 1 adduct, 7-oxabicyclo [2.2.1]hept-5-ene-2,3-dicarboxyHc anhydride (4) in exceUent yield. Other strong dienophiles also add to furan (88). Although both endo and exo isomers are formed initially, the former rapidly isomerize to the latter in solution, even at room temperature. The existence of a charge-transfer complex in the system has been demonstrated (89,90). 

The electronic structures of the diene and dienophile also influence the regioselectivity of the reaction The regiochemistry of Diels-Alder products 27, 29. and 31, derived from the variously substituted dienes 25, 28, and 30, is illustrated by the scheme in the margin. 

The soft-soft interaction of filled with empty orbitals is the major interaction in the transition state because there is little hard-hard attraction. In an unsubstituted system two soft-soft interactions stabilize the transition state The filled tl)2 molecular orbital of the diene interacts with the unfilled jt of the dienophile also the empty ips of the diene interacts with the filled Jt of the dienophile. Figure 12.19 gives the interaction diagram. 

Diels-Alder reactions [1, 246, after citation of ref. 9J. The dienophile also reacts with tropone to give the product of 1,4-addition.9a... 

Reactions performed with methyl vinyl ketone and metacrolein as ethylenic dienophiles also revealed the clear advantage of SMWI conditions over conventional heating (Table 9.2, entries 4-6) [31]. In the reaction of isoprene with methyl vinyl ketone (Table 9.2, entry 6), selectivity for the para adduct (54%) was much better than when conventional heating was used (26%), probably owing to the reduction of the reaction time. 

Hetero atom-containing dienophiles also take part in the intramolecular Diels-Alder reaction [121-122]. With o-quinone methides [123], cyclization proceeds at the temperature required to generate the diene. The reaction of a nitrile as a dienophile with a simple acyclic diene has also been reported [124]. 

The D-A reactions of acyclic dienes with acyclic dienophiles also give endo-and exo-products. For example, D-A reaction of l-deuterio-l,3-pentadiene 46 with rrani-3-penten-2-one 47 gives endo 48 and exo 49 products as shown. 

Alkynic dienophiles also work well, e.g. ethyl propiolate and (1) produce the expected cyclohexadiene ester in 77% yield. In addition to simple dienophiles, a number of allenic dienophiles have also been utilized, as shown in Table 2. Cyclic dienophiles, enones, lactams, etc., are often reacted with (1) to give fused bicyclic systems, but generally the yields are only in the 25-45% range, e.g. reaction of (1) with (13) gives (14) in 27% 3field (eq 2). ... 

However, in contrast to quassin, the synthesis of glaucarubinone and its congeners required the installation of a hydroxymethyl group (or its surrogate) at C(8) (cf. 5.20, Y = OH). It was decided that a formyl group would not only serve this purpose but also increase the reactivity of the dienophile. Unfortunately, the incorporation of an additional carbonyl onto the dienophile also compromised the stereochemistry at C(14) by providing an alternative mode for endo-cycloaddition. As noted already, the breakthrough came when 5.22 was combined with the diene carboxylate 5.10 in... 

Diels-Alder reactions can be divided into normal electron demand and inverse electron demand additions. This distinction is based on the way the rate of the reaction responds to the introduction of electron withdrawing and electron donating substituents. Normal electron demand Diels-Alder reactions are promoted by electron donating substituents on the diene and electron withdrawii substituents on the dienophile. In contrast, inverse electron demand reactions are accelerated by electron withdrawing substituents on the diene and electron donating ones on the dienophile. There also exists an intermediate class, the neutral Diels-Alder reaction, that is accelerated by both electron withdrawing and donating substituents. 

The FMO coefficients also allow cpralitative prediction of the kinetically controlled regioselectivity, which needs to be considered for asymmetric dienes in combination with asymmetric dienophiles (A and B in Scheme 1.1). There is a preference for formation of a o-bond between the termini with the most extreme orbital coefficients ... 

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. 

Fortunately, azachalcone derivatives (2.4a-g, Scheme 2.4) turned out to be extremely suitable dienophiles for Lewis-add catalysed Diels-Alder reactions with cyclopentadiene (2.5). This reaction is outlined in Scheme 2.4 and a large part of this thesis will be devoted to the mechanistic details of this process. The presence of a chromophore in 2.4 allows kinetic studies as well as complexation studies by means of UV-vis spectroscopy. Furthermore, the reactivity of 2.4 is such that also the... 

Catalysis by the four metal ions was also compared with respect to their sensitivity towards substituents in the dienophile. To this end the equilibrium constants for complexation of2.4a-g to the four different ions were determined. The results are shown in Table 2.6. 

In summary, for the most active of catalysts, the copper(II) ion, the diamine ligands that were investigated seriously hamper catalysis mainly by decreasing the efficiency of coordination of the dienophile. With exception of the somewhat deviant behaviour of N,N -dimethylethylenediamine, this conclusion also applies to catalysis by Ni" ions. Hence, significant ligand-accelerated catalysis using the diamine ligands appears not to be feasible. 

On the basis of the studies described in the preceding chapters, we anticipated that chelation is a requirement for efficient Lewis-acid catalysis. This notion was confirmed by an investigation of the coordination behaviour of dienophiles 4.11 and 4.12 (Scheme 4.4). In contrast to 4.10, these compounds failed to reveal a significant shift in the UV absorption band maxima in the presence of concentrations up to one molar of copper(ir)nitrate in water. Also the rate of the reaction of these dienophiles with cyclopentadiene was not significantly increased upon addition of copper(II)nitrate or y tterbium(III)triflate. 

The use of dienophile 5.1 also allows study of the effect of micelles on the Lewis-acid catalysed reaction. These studies are described in Section 5.2.2. and represent the first in-depth study of Lewis-acid catalysis in conjunction with micellar catalysis , a combination that has very recently also found application in synthetic organic chemistry . ... 

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