Lewis acid catalyzed Diels—Alder reaction regioselectivity

This chapter will mostly deal with the applications of the Lewis-acid-catalyzed Diels Alder reaction to organic synthesis and the influence of Lewis acids on reactivity, stereoselectivity and regioselectivity of the cycloadditions. 

SbCls improves the regioselectivity in the Lewis acid-catalyzed Diels-Alder reaction of toluquinone with 1,3-dienes (Scheme 14.25) [63]. The greater steric demand of SbCls compared with other Lewis acids would favor the less hindered transition state. Acyclic isopentenoids are cyclized under HF-SbFs catalysis to yield monocyclic or bicychc derivatives (Scheme 14.26) [64]. 

Tamariz et al. developed an access to 1-methoxycarbazoles 225 via hydrolysis of 3-arylbenzoxazol-2-ones 223 and subsequent palladium(II)-mediated oxidative cyclization of the resulting diarylamines 224 (Scheme 54) [213, 214]. The required benzoxazol-2-ones 223 are obtained by regioselective Lewis acid-catalyzed Diels-Alder reaction of 4,5-dimethylene-3-aryl-l,3-oxazolidm-2-ones with alk-enes followed by aromatization using 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ). 

Lewis acids such as zinc chloride, boron trifluoride, aluminum chloride, and diethylaluminum chloride catalyze Diels-Alder reactions.8 The catalytic effect is the result of coordination of the Lewis acid with the dienophile. The complexed dienophile is more electrophilic and more reactive toward electron-rich dienes. The mechanism of the cycloaddition is still believed to be concerted, and high stereoselectivity is observed.9 10 Lewis acid catalysts also usually increase the regioselectivity of the reaction. 

The use of catalysts for a Diels-Alder reaction is often not necessary, since in many cases the product is obtained in high yield in a reasonable reaction time. In order to increase the regioselectivity and stereoselectivity (e.g. to obtain a particular endo- or exo-product), Lewis acids as catalysts (e.g. TiCU, AICI3, BF3-etherate) have been successfully employed." The usefulness of strong Lewis acids as catalysts may however be limited, because they may also catalyze polymerization reactions of the reactants. Chiral Lewis acid catalysts are used for catalytic enantioselective Diels-Alder reactions. ... 

The discovery that Lewis acids can promote Diels-Alder reactions has become a powerful tool in synthetic organic chemistry. Yates and Eaton [4] first reported the remarkable acceleration of the reactions of anthracene with maleic anhydride, 1,4-benzoquinone and dimethyl fumarate catalyzed by aluminum chloride. The presence of the Lewis-acid catalyst allows the cycloadditions to be carried out under mild conditions, reactions with low reactive dienes and dienophiles are made possible, and the stereoselectivity, regioselectivity and site selectivity of the cycloaddition reaction can be modified [5]. Consequently, increasing attention has been given to these catalysts in order to develop new regio- and stereoselective synthetic routes based on the Diels-Alder reaction. 

Because of their previous findings that a,/l-unsaturated thioesters were more reactive than their ester counterparts in Diels-Alder reactions85, Hart and coworkers86 performed a systematic study of the cycloaddition reactions of a,/l-unsaturated thioesters and a,ft-unsaturated selenoesters with several dienes. Thermal reactions were compared with Lewis acid catalyzed reactions at room temperature (equation 28 and Table 2). The results clearly demonstrated that use of a Lewis acid enhanced the regioselectivity (entries 1 vs 2, 3 vs 4, 5 vs 6 and 7 vs 8) as well as the endo (with respect to the thioester or selenoester group) selectivity (entries 5 vs 6 and 7 vs 8). 

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. 

The Diels-Alder cycloaddition reaction of dihydropyran with acrolein was performed in the presence of various H-form zeolites such as H-Faujasites, H-p, H-Mordenites which differ both in their shape selective as well as their acidic properties. The activity of the different catalysts was determined and the reaction products were identified. High 3delds in cycloadduct were obtained over dealuminated HY (Si/Al=15) and Hp (Si/Al=25) compared to HM (Si/Al=10). These results were accounted for in terms of acidity, shape selectivity and microporosity vs mesoporosity properties. The activity and the regioselectivity were then discussed in terms of frontier orbital interactions on the basis of MNDO calculations for thermal and catalyzed reactions by complexing the diene and the dienophile with Bronsted and Lewis acidic sites. From these calculations, Bronsted acidic sites appeared to be more efficient than Lewis acidic sites to achieve Diels-Alder reactions. 

Diels-Alder Reactions. Bp3-OEt2 is used to catalyze and reverse the regiospecificity of some Diels-Alder reactions, e.g. with pen-hydroxylated naphthoquinones, sulfur-containing conpounds, the reaction of 1-substituted trans-1,3-dienes with 2,6-dimethylbenzoquinones, and the reaction of 6-inethoxy-l-vinyl-3,4-dihydronaphthalene with p-quinones. BFs-OEta has a drastic effect on the regioselectivity of the Diels-Alder reaction of quinoline- and isoquinoline-5,8-dione with piperylene, which produces substituted azaanthraquinones. This Lewis acid is the most effective catalyst for the Diels-Alder reaction of furan with methyl acrylate, giving high endo selectivity in the 7-oxabicyclo[2.2.1]heptene product (eq 35). ... 

Similar to the Diels-Alder reaction, Lewis acid-catalyzed approaches were applied to intra- and intermolecular ene reactions, which served to diminish the temperatures required to promote the reaction and improved the selectivity. For example, reaction of 2-Me-2-propene with methyl propiolate provided a mixture of 24 and 25 at 220 °C, but proved higher yielding and more regioselective providing exclusively 24 when a Lewis acid was used. ... 

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