Diels-Alder reactions by Lewis acids

Catalysis of Diels-Alder Reactions by Lewis Acids 

The stereoselectivity of any particular D-A reaction depends on the details of the TS structure. The structures of several enone-Lewis acid complexes have been determined by X-ray crystallography. The site of complexation is the carbonyl oxygen, which maintains a trigonal geometry, but with somewhat expanded angles (130°-140°). The Lewis acid is normally anti to the larger carbonyl substituent. Boron trifluoride complexes are tetrahedral, but Sn(IV) and Ti(IV) complexes can be trigonal bipyramidal or octahedral. The structure of the 2-methylpropenal-BF3 complex is illustrative.  

Chelation can favor a particular structure. For example, C-acryloyl lactates adopt a chelated structure with TiCL. ° 

Lewis acid catalysis can also be applied to inverse electron demand D-A reactions, but with the proviso that the strongest interaction must be with the diene in this case. 

Metal cations can catalyze reactions of certain dienophiles. For example, Cu strongly catalyzes addition reactions of 2-pyridyl styryl ketones, presumably through a chelate. DFT (B3LYP/6-31G ) computations indicate that this reaction shifts to a stepwise ionic mechanism in the presence of the Lewis acid.  

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From 1928 when Otto Diels and Kurt Alder [1] made their extraordinary discovery until 1960 when Yates and Eaton [2] reported the acceleration of the Diels-Alder cycloadditions by Lewis acid catalysts, these reactions were essentially carried out under thermal conditions owing to the simplicity of the accomplishing thermal process. Since then a variety of methods have been developed to accelerate the reactions. The reaction between 1,3-butadiene and ethylene (Equation 2.1) is a typical example of a thermal Diels-Alder cycloaddition. 

Lewis acid-mediated reactions can be classified into two groups (Fig. 4). In the first (type 1) the complex between substrate and Lewis-acid reagent produces the product. Claisen rearrangement promoted by a Lewis-acid catalyst is a typical example of this type. Some complexes formed between Lewis acids and substrates are, however, stable enough to react with a variety of reagents from outside the system to generate the product (type 2). The Diels-Alder reaction between Lewis acid-activated unsaturated carbonyl compounds and dienes is an example of type 2 reactions. 

The high endo selectivity of aromatic aldehydes is also a result of their capability to participate in secondary orbital interactions. The mixing of the LUMO of benzaldehyde with the HOMO of the diene can form secondary orbital overlap which lowers the energy of the endo transition state. The electron-withdrawing effect of the catalyst [e.g. Eu(fod)3] on the aldehyde further enhances secondary orbital overlap with aromatic aldehydes by an additional reduction of the LUMO energy (Figure 2). Similar arguments have been made to rationalize the increase in endo selectivity of homo Diels-Alder reactions when Lewis acids are used as catalysts.Secondary orbital interactions are, however, absent when the dienophile is an aliphatic aldehyde in such reactions the cis (endo) stereoselectivity is based solely on steric interactions. 

The endo exo selectivity for the Lewis acid-catalyzed carbo-Diels-Alder reaction of butadiene and acrolein deserves a special attention. The relative stability of endo over exo in the transition state accounts for the selectivity in the Diels-Alder cycloadduct. The Lewis acid induces a strong polarization of the dienophile FMOs and change their energies (see Fig. 8.2) giving rise to better interactions with the diene, and for this reason, the role of the possible secondary-orbital interaction must be considered. Another possibility is the [4 + 3] interaction suggested by Singleton... 

Bonnesen PV, Puckett CL, Honeychuck RV, Hersh WH (1989) Catalysis of Diels-Alder reactions by low oxidation state transition-metal Lewis acids fact and fiction. J Am Chem Soc 111 6070-6081... 

The activation of various reactions by Lewis acids is now an everyday practice in synthetic organic chemistry. In contrast, solvent effects on Lewis acid catalysed Diels-Alder reactions have received much less attention. A change in the solvent can affect the association step leading to the transition structure. Ab initio calculations on the Diels-Alder reaction of cyclopentadiene and methyl vinyl ketone in aqueous media showed that there is a complex of the reactants which also involves one water molecule119. In an extreme case solvents can even impede catalysis120. The use of inert solvents such as dichloromethane and chloroform for synthetic applications of Lewis acid catalysed Diels-Alder reactions is thus well justified. General solvent effects, in particular those of water, will be discussed in the following section. 

The efficient and selective catalysis of some Diels-Alder reactions by lanthanide P-diketonate complexes has been known since 1975 [226, 227]. The fluorinated p-diketonate complexes Ln(fod)3 (cf. Scheme 12.5) selectively catalyze the Danishefsky transformation (Scheme 12.23) as a consequence of their mild Lewis acidity. Importantly, zeolites and Lewis acid modified silica or alumina also catalyze Diels-Alder reactions [228-232]. 

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. 

Copper Lewis acids also find utility in Diels-Alder reactions in aqueous media. Engberts et al. have reported large rate acceleration of Diels-Alder reactions by Cu(N03)2 in water [89]. The higher Lewis acidity of Cu(II) compared with Co(II), Ni(II), and Zn(II) in aqueous media was also established in their study. An enantio-selective variant of the Diels-Alder reaction using a catalyst derived from L-arbine and Cu(OTf)2 (210) in water was reported recently (Sch. 47) [90]. 

TABLE 8. Rate and selectivity enhancements of Diels-Alder reactions by addition of Lewis acids ... 

Promotion of the Diels-Alder reaction by a substoichiometric amount of chiral Lewis acid has developed to a relatively high level of sophistication as a result of the extensive research in this field. In the interest of providing mechanistic insight into highly efficient systems, the discussion will be limited to systems which provide synthetically useful levels of enantioselection (typically greater than 90%) [43]. Even with this restriction, the reader will note remarkable breadth in the chiral complexes that have been studied. As a result of the unique characteristics different metals confer to Lewis acidic complexes, it is advantageous to discuss each metal in turn. 

Roussel C, Lid n A, Chanon M, Metzger J, Sandstrbm J (1976) J Am Chem Soc 98 2847 Honda Y, Date T, Hiramatsu H,Yamauchi M (1997) Chem Commun 1411 For a more in-depth discussion of this observation, see Yamauchi M, Honda Y, Matsuki N, Watanabe T, Date K, Hiramatsu H (1996) J Org Chem 61 2719 For a general reference on catalysis of the Diels-Alder reaction by achiral transition metal Lewis acids, see Bonnesen PV, Puckett CL, Honeychuck RV, Hersh WH (1989) J Am Chem Soc 111 6070... 

Lewis acid catalysts increase the reactivity of dienophiles in Diels-Alder reactions by complexing to basic sites on the dienophile. ° The Lewis acid lowers the LUMO of the adjacent ir-system, which strengthens the overlap between the LUMO of the dienophile and the HOMO of the diene. In 1979 Scheeren reported that ZnCh catalyzes the cyclocondensation reaction of unactivated aldehydes with l-methoxy-3-(trimethylsilyloxy)-l,3-butadiene. Experimental details of this reaction, however, were not fully documented. In 1982 Scheeren also reported the use of aluminum alkoxydichlorides as catalysts... 

Two different Lewis acids, SnCl and MejAlCl, exert opposite stereochemical results in a hetero-Diels-Alder reaction by conformational effects. ... 

Since the first report of chiral oxazaborolidine-based Bronsted acid-assisted chiral Lewis acid (BLA) for enantioselective Diels-Alder reactions by Corey and coworkers... 

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