Hydrogen-bonding activation Diels-Alder reactions, dienes

The pseudothermodynamic analysis of solvent elfects in 1-PrOH-water mixtures over the whole composition range (shown in Figure 7.3) depicts a combination of thermodynamic transfer parameters for diene and dienophile with isobaric activation parameters that allows for a distinction between solvent elfects on reactants (initial state) and on the activated complex. The results clearly indicate that the aqueous rate accelerations are heavily dominated by initial-state solvation effects. It can be concluded that for Diels-Alder reactions in water the causes of the acceleration involve stabilization of the activated complex by enforced hydrophobic interactions and by hydrogen bonding to water (Table 7.1, Figure 7.4). °... 

On the other hand, lower reaction temperature (0-30 °C) was indispensable to decrease the background reaction. Under these conditions, a wide range of other 0C, 3-unsaturated ketones and substituted 2-pyrones had been converted into bicyclic chiral compounds 17 in high yield, diastereomeric ratio, and enantiomeric excess (Table 10.8). Interestingly, theauthors noted that, incontrastto 2-pyrone, electron-rich dienes bearing neither a hydrogen-bond acceptor nor donor such as cyclopentadiene and cyclohexadiene were inactive for the Diels-Alder reaction with benzylideneace-tone catalyzed by lp and TFA. They propose that the activation of 2-pyrone by the multifunctional amine IP is also required for the D-A reaction to occur [30],... 

The factors that determine the steric course of these cycloaddition reactions are still not completely clear. It appears that a number of forces operate in the transition state and the precise composition of the product depends on the balance among these. The preference for the endo adduct, in which the dienophile substituents are oriented over the residual unsaturation of the diene in the transition state, has been rationalized by Woodward and Hoffmann in terms of secondary orbital interactions. In this explanation, the atomic orbital at C-2 (and/or C-3) in the HOMO of the diene interacts with the atomic orbital of the activating group in the LUMO of the dienophile. However, there is no evidence for this secondary orbital interaction and the stereoselectivities in the Diels-Alder reaction can be explained in terms of steric interactions, solvent effects, hydrogen-bonding, electrostatic and other forces (3.70). ... 

Wu and his co-workers reported an experimental and theoretical study on the hydrogen-bond-promoted enantioselective hetero-Diels-Alder reaction (HAD) of Danishefsky s diene 105 with benzaldehyde 106, Scheme 3.37 [52], The reaction was achieved catalytically by a series of a,ct,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) derivatives through hydrogen-bonding activation and afforded 2-phenyl-2, 3-dihydro-4H-pyran-4-one 108 in good enantioselectivity. 

In 2004 the same research group showed that TADDOLs 2 were able to catalyse other reactions via hydrogen-bonding activation, for example the Diels-Alder reaction between diene 1 and substituted acroleins 5 (Scheme 24.3), for this reaction 1-naphthyl-TADDOL 2a was the best catalyst. 

Du HF, Zhao DB, Ding KL (2004) Enantioselective Catalysis of the Hetero-Diels-Alder Reaction Between Brassard s Diene and Aldehydes by Hydrogen-Bonding Activation A One-Step Synthesis of (5)-(-t)-Dihydrokawain. Chem Eur J 10 5964... 

In 2008, the first asymmetric Diels-Alder reaction of 3-vinylindoles 91 and maleimides 80 with a bifunctional thiourea catalyst (92) was realized by Bernardi and coworkers (Scheme 38.25) [39]. The resultant highly-enantioenriched fused heterocycles are very useful for the synthesis of biologically important natural or unnatural alkaloids. As shown in the proposed transition state N, catalyst 92 probably activates the diene with the basic moiety and activates the dienophile with the thiourea moiety through hydrogen bonding interactions. 

Recently, chiral bis-phosphoric acid 77 bearing a new chiral scaffold with triple axial chirality assisted by intramolecular hydrogen-bonding between two phosphoric acid moieties was designed as a new chiral Bronsted acid catalyst by the Terada group [33], Application of this catalyst in the Diels-Alder reaction between substituted acroleins 66 and amido-dienes 76 produced the corresponding cycloadducts 78 with excellent enantioselectivities (Scheme 38.22). In comparison with the mono-phosphoric acid, bis-phosphoric acid 77 showed obviously higher catalytic activity and selectivity. 

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