Lewis acid catalyst, in the Diels-Alder reaction

Cycloaddition of 2-cyanoalk-2-enones with several conjugated dienes proceeded under zinc chloride catalysis.636 Zinc halides have also shown reactivity with phenylacetylenes.637 Zinc chloride is an effective Lewis acid catalyst in the Diels Alder reactions of the keto esters and the effects on stereochemistry of catalysts used have been examined.638... 

Copper(II) complexes of amino acids have been explored as chiral Lewis acid catalysts in the Diels-Alder reaction of 3-phenyl-l-(2-pyridyl)-2-propen-l-one with cyclopentadiene. The best results were obtained using /V-methyl-/.-tryptophan, but more interestingly, the highest ee values for the major endo adduct were achieved in aqueous solution273. 

C2-Symmetric tridentate bis(oxazolinyl)pyri-dine-Cu(Il) complexes, introduced by Evans et al., can function as effective chiral Lewis acid catalysts in the Diels-Alder reaction [15a]. When applied to catalytic asymmetric aldol reactions [15], remarkable results were achieved (Scheme 8) [15a]. Only 0.5 mol % of catalyst 48 was needed for the reaction of 30 with the silylketene thioacetal 47 to yield after deprotection 49 in 99 % chemical yield. The ee values were determined to be 99 %. Today, catalysts... 

Unlike main group Lewis acids, catalysts for the Diels-Alder reaction containing metals reviewed in this chapter are of recent origin. Major expectations in this area are linked to desirable properties such as catalyst stabiUty, selectivity and effectiveness, tolerance of impurities (e.g. water), and asymmetric modification. Over the past few years an increasing number of literature reports show this to be an area of high potential. 

Diels-Alder reactions. Many excellent Lewis acid catalysts for the Diels-Alder reaction are formed from enantiomeric binaphthols and substituted binaph-thols. Ytterbium-, aluminum-, and titanium-based species have been developed. A chiral iron catalyst" is also quite effective, but a zirconocene-based catalyst is disappointing in terms of asymmetric induction. 

In one of the first examples of a specific synthetic application of a lanthanide shift reagent, Eu(fod)3 acted as a mild Lewis acid catalyst in hetero-Diels-Alder reactions (Bednarski and Danishefsky, 1983a). 

The importance of Lewis acid catalysis in the Diels-Alder reactions is well recognized. MeaSiOTf (la), which is a most versatile silicon Lewis acid catalyst, is effective in the Diels-Alder reaction of activated 1,3-dienes, while it cannot catalyze the reaction of simple 1,3-dienes [8, 9]. However, the recent developments of stronger silicon Lewis acids overcome the limitation. 

The /lomo-Diels-Alder reaction is a [2 + 2 + 2] cycloaddition of a 1,4-diene with a dienophile which produces two new bonds and a cyclopropane ring. This reaction is an example of a multi-ring-forming reaction that to date has found few applications in synthesis, since the use of 1,4-dienes has been limited mainly to bridged cyclohexa-1,4-dienes and almost exclusively to norbornadiene. Lewis-acid catalysts accelerate /lowo-Diels-Alder reactions and increase the selectivity for the [2 + 2 + 2] vs. [2 + 2] cycloaddition. 

Efficient asymmetric Diels-Alder reactions catalyzed by chiral Lewis acids have recently been reported [34]. Although rare earth compounds were expected to be promising Lewis acid reagents, few asymmetric reactions catalyzed by chiral rare earth Lewis acids were reported [35], although rare earth triflates, especially Yb(OTf)3 and Sc(OTf)3, are good catalysts in the Diels-Alder reactions of a variety of dienophiles with cyclic and acyclic dienes (as mentioned in Section 19.2.6). 

Seebach s TADDOL auxiliaries, derived from tartrate (chapter 23), combine well with Ti(IV) to make an effective Lewis acid catalyst 130 for Diels-Alder reactions. The reaction of isoprene with the doubly activated amide dienophile 128 gives one adduct 129 in good yield.29 Polymer supported versions of this catalyst are available. 

The compounds thus obtained have been used as starting materials for chiral crown ethers h 3> 15 (see Section 5.2.), having applications as enantioselective catalysts in Michael additions (Sections D.1.5.2.1. and D.1.5.2.4.). 3,3 -Dimethyl- and 3,3 -diphenyl-2,2 -dihydroxy-l,T-binaph-thyls 8 and 3 have been applied as ligands for the synthesis of chiral Lewis acids used as stereoselective catalysts in the Diels Alder reaction (Section D.1.6.1.1.1.3.). 

Thus, the reaction in aqueous Cu(N03)2 solution proceeded about 800 times faster than in water alone and 250000 times faster than in acetonitrile. This Lewis-acid-catalyzed aqueous Diels-Alder reaction presumably occurs via a transition state such as 2.50 with bidentate complexation to the metal as shown. In a related study, Kobayashi reported that scandium triflate can be used as a water-tolerant Lewis-acid catalyst for a Diels-Alder reaction in (9 1) tetrahydrofuran-water (THF-H2O) [30], though this mixed solvent system cannot take advantage of the hydrophobic effect observed in pure water or highly aqueous mixtures. 

In 2007, Corey group has reinvestigated Lewis acid activation of the chiral oxazaborolidine (la) instead of the use of the strong Bronsted acid triflimide, leading to the identification of AlBr3-(la) complex (10) as an unusually powerful and effective chiral Lewis acid catalyst for enantioselective Diels-Alder reactions (Scheme 1.15) [21]. 

A combination of the promoting effects of Lewis acids and water is a logical next step. However, to say the least, water has not been a very popular medium for Lewis-acid catalysed Diels-Alder reactions, which is not surprising since water molecules interact strongly with Lewis-acidic and the Lewis-basic atoms of the reacting system. In 1994, when the research described in this thesis was initiated, only one example of Lewis-acid catalysis of a Diels-Alder reaction in water was published Lubineau and co-workers employed lanthanide triflates as a catalyst for the Diels-Alder reaction of glyoxylate to a relatively unreactive diene . No comparison was made between the process in water and in organic solvents. 

Many Lewis-acid catalysts have been studied and used in the Diels-Alder reactions, ranging from the more commonly used strong Lewis acids such as AICI3, TiCU, SnCU, ZnCli, ZnBri, etc., to the milder lanthanide complexes and to the chiral catalyst. 

Silica gel [11] or alumina [11a, 12] alone, or silica and alumina together modified by Lewis-acid treatment [13] and zeolites [14], have been widely used as catalysts in Diels-Alder reactions, and these solids have also been tested as catalysts in asymmetric Diels-Alder reactions [12,13b,14]. Activated silica gel and alumina at 140 °C were used [15] to catalyze the asymmetric cycloaddition of (-)-menthyl-N-acetyl-a, S-dehydroalaninate (3) (R = NHCOMe) with cyclopentadiene in the key step for synthesizing optically active cycloaliphatic a-amino acids. When the reactions were carried out in the absence of solvent, a higher conversion was obtained. Some results are reported in Table 4.5 and compared with those obtained by using silica and alumina modified by treatment with Lewis acids. Silica gel gives a reasonable percentage of conversion after 24 h with complete diastereofacial selectivity in exo addition. 

The optically active a-sulfinyl vinylphosphonate 122 prepared in two different ways (Scheme 38) is an interesting reagent for asymmetric synthesis [80]. This substrate is an asymmetric dienophile and Michael acceptor [80a]. In the Diels-Alder reaction with cyclopentadiene leading to 123, the endo/exo selectivity and the asymmetry induced by the sulfinyl group have been examined in various experimental conditions. The influence of Lewis acid catalysts (which also increase the dienophilic reactivity) appears to be important. The 1,4-addition of ethanethiol gives 124 with a moderate diastereoselectivity. 

Recently, catalytic asymmetric Diels-Alder reactions have been investigated. Yamamoto reported a Bronsted-acid-assistcd chiral (BLA) Lewis acid, prepared from (R)-3-(2-hydroxy-3-phcnylphenyl)-2,2 -dihydroxy-1,1 -binaphthyl and 3,5A(trifluoromethy I) - be nzeneboronic acid, that is effective in catalyzing the enantioselective Diels-Alder reaction between a,(3-enals and various dienes.62 The interesting aspect is the role of water, THF, and MS 4A in the preparation of the catalyst (Eq. 12.19). To prevent the trimerization of the boronic acid during the preparation of the catalyst, the chiral triol and the boronic acid were mixed under aqueous conditions and then dried. Using the catalyst prepared in this manner, a 99% ee was obtained in the Diels-Alder reaction... 

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