Cycloaddition Aluminum Lewis acid-catalyzed

Fluorine-containing aldehydes, ketones and acid fluorides undergo photoinitiated cycloaddition reactions with fluorinated alkenes to give oxetanes.90 91 The addition of hexafluoroacetone (11) to fluoroalkenes can also be performed in the presence of the Lewis acid, aluminum chloride fluoride.92-1 22-1 23 Unlike the photochemical cycloaddition of hexafluoroacetone with trifluoroethene, the Lewis acid catalyzed addition is regioselective.92 Fluorooxetanes (c. g., 14) have also been synthesized by the addition of formaldehyde to fluoroalkenes in hydrogen fluoride.94 Examples of the formation of fluorooxetanes by [2 + 2]-cycloaddition reactions arc-given in Table 8. 

Asymmetric Dieh-Alder Reactions. The commercial availability of either enantiomer of camphorsulfonic acid has made it quite useful in asymmetric Diels-Alder reactions. Reaction of the sultone (generated from CS A) with Lithium Diisopropylamide followed by esterification and (3-elimination yields the crystalline acrylate (eq 14). The Lewis acid-catalyzed [4 + 2] cycloaddition of 1,3-dienes with this acrylate affords the corresponding scalemic adduct which can be reduced with Lithium Aluminum Hydride to yield an enantiomerically pure alcohol (eq 15). ... 

Asymmetric ketene-aldehydes cycloaddition leading to the enantiomerically enriched (3-lactones (83) is catalyzed effectively by trifluoromethanesulfonylated aluminum Lewis acid (80), which controls the stereochemistry much more efficiently than the corresponding tosylated catalyst (Scheme 5.22) [7]. The lactones (83) are useful precursors for the enantiomerically enriched (3-amino acids (84). 

Early applications of chiral Lewis acid catalyzed stereoselective Diels Alder reactions used either boron- or aluminum-derived systems in carbocyclic ring formation18 1Q, or studied the effect of chiral shift reagents, such as Eu(hfc)3, in hetero-Diels-Alder cycloadditions of carbonyl compounds to dienes20 23,77, 78. The latter type of transition metal catalyzed addition is classified as heterocarboration and is described in Section 1.5.8.4. 

Menthol [(—)-l] has been used as a chiral ligand for aluminum in Lewis acid catalyzed Diels-Alder reactions with surprising success2 (Section D.l.6.1.1.1.2.2.1). The major part of its application is as a chiral auxiliary, by the formation of esters or ethers. Esters with carboxylic acids may be formed by any convenient esterification technique. Esters with saturated carboxylic acids have been used for the formation of enolates by deprotonation and subsequent addition or alkylation reactions (Sections D.l.1.1.3.1. and D.l.5.2.3.), and with unsaturated acids as chiral dienes or dienophiles in Diels-Alder reactions (Section D. 1.6.1.1.1.), as chiral dipolarophiles in 1,3-dipolar cycloadditions (Section D.l.6.1.2.1.), as chiral partners in /(-lactam formation by [2 + 2] cycloaddition with chlorosulfonyl isocyanate (SectionD.l.6.1.3.), as sources for chiral alkenes in cyclopropanations (Section D.l.6.1.5.). and in the synthesis of chiral allenes (Section B.I.). Several esters have also been prepared by indirect techniques, e.g.,... 

Thermal and Lewis acid-catalyzed reactions of 1-thia-l,3-dienes with chiral a,P-unsaturated carboxylic acid derivatives lead to thiopyrans. The cycloadditions of chiral a,p-unsaturated oxazolidinones in the presence of aluminum Lewis acids lead to encouraging stereoselectivities. Cleavage of the chiral auxiliaries was achieved by treatment with LiAlHi. 

As important hetero Diels-Alder reactions catalyzed by aluminum Lewis acid, two kind of reactions, namely, [4 + 2] cycloaddition of Danishefski s diene with carbonyls and [4 + 2] cycloaddition of nitroalkenes with electronic rich alkenes, have been well known. The former reaction provides highly functionalized pyrones. As the first example of pyrone synthesis through catalytic asymmetric hetero Diels-Alder reaction with chiral aluminum complexes, in 1987, Quimpere and Jankowski reported the reaction of oxomalonate with 1-methyl-1,3-butadiene using Koga s catalyst (48). However, the asymmetric induction and chemical yield were quite poor (Scheme 6.147) [175]. 

As another type of hetero Diels-Alder reaction catalyzed by aluminum Lewis acid, Denmark and coworkers recently demonstrated rich chemistry on [4 + 2]cycloaddition of nitroalkenes with vinyl ethers. The reaction of nitroalkenes having an external alkene moiety with vinyl ether proceeds via intermolecular [4 + 2]cycloaddition followed by intramolecular [3 + 2]cycloaddition to give a mixture of tricyclic nitrosoacetals (150) (Scheme 6.150) [178]. In this reaction, stereoselectivity was affected by Lewis acid. In the case of bulky aluminum Lewis acids, such as MAPH and ATPH, (159b) was obtained as a major product. On the other hand, the use of less bulky titanium Lewis acids, for example, TiCU and TiCl3(Oi-Pr), resulted in selective formation of (150a). 

The mechanism of the cycloaddition reaction of benzaldehyde 2a with Danishefsky s diene 3a catalyzed by aluminum complexes has been investigated theoretically using semi-empirical calculations [14]. It was found that the reaction proceeds as a step-wise cycloaddition reaction with the first step being a nucleophilic-like attack of Danishefsky s diene 2a on the coordinated carbonyl compound leading to an aldol-like intermediate which is stabilized by interaction of the cation with the oxygen atom of the Lewis acid. The next step is the ring-closure step, giving the cycloaddition product. 

The enantioselective inverse electron-demand 1,3-dipolar cycloaddition reactions of nitrones with alkenes described so far were catalyzed by metal complexes that favor a monodentate coordination of the nitrone, such as boron and aluminum complexes. However, the glyoxylate-derived nitrone 36 favors a bidentate coordination to the catalyst. This nitrone is a very interesting substrate, since the products that are obtained from the reaction with alkenes are masked a-amino acids. One of the characteristics of nitrones such as 36, having an ester moiety in the a position, is the swift E/Z equilibrium at room temperature (Scheme 6.28). In the crystalline form nitrone 36 exists as the pure Z isomer, however, in solution nitrone 36 have been shown to exists as a mixture of the E and Z isomers. This equilibrium could however be shifted to the Z isomer in the presence of a Lewis acid [74]. 

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. 

Several aluminum- and titanium-based compounds have been supported on silica and alumina [53]. Although silica and alumina themselves catalyze cycloaddition reactions, their catalytic activity is greatly increased when they complex a Lewis acid. Some of these catalysts are among the most active described to date for heterogeneous catalysis of the Diels-Alder reactions of carbonyl-containing dienophiles. The Si02-Et2AlCl catalyst is the most efficient and can be... 

This procedure describes the preparation and application of an effective chiral catalyst for the enantioselective Diels-Alder reaction.11 The catalyst is derived from optically active 1,2-diphenylethylenediamine, the preparation of which (either antipode) was described in the preceding procedure. The aluminum-based Lewis acid also catalyzes the cycloaddition of crotonoyl oxazolidinones with cyclopentadiene,11 and acryloyl derivatives with benzyloxymethylene-cyclopentadiene. The latter reaction leads to optically pure intermediates for synthesis of prostaglandins.11... 

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. 

Interestingly, in these cases, the use of aluminum trichloride as a Lewis acid catalyst promoted regiospecificity and only the l,l-dicyclopropyl-2-mcthylenecyclobutanes were obtained (see Section 1.3.4.2.). Furthermore, the catalyzed cycloadditions proceeded under milder conditions (room temperature vs. 200 °C for noncatalyzed cycloadditions). In the same study, the cycloaddition of 1,1-dimethylallene (14) with tetracyanoethene proceeded regiospecifically giving 3-(l-methylethylidene)cyclobutane-l,l,2,2-tetracarbonitrile (15) in 71% yield.11,12... 

Cycloadditions. The asymmetric Diels-Alder reaction of phenylmenthyl acrylate with 5-benzyloxymethyl-cyclopentadiene in the presence of Aluminum Chloride produces an 89% yield of the endo cycloadduct (eq 1), accompanied by 7% of the exo adduct. This provides a useful intermediate for the preparation of various prostaglandins. The Tin(IV) Chloride and Titanium(IV) Chloride catalyzed reactions with Cyclopenta-diene deliver a mixture of endo and exo adducts in 89% de, and 90% de, respectively (eq 2). The TiCU reaction gives an 89 11 endo. exo ratio, while the SnCU reaction gives an 84 16 endoiexo ratio. From a practical point of view, the titanium and tin catalysts are the best of the various Lewis acids surveyed. The use of TiCl4 is also the most effective for the reaction of the acrylate... 

Significantly stronger Lewis acid aluminum chlorofluoride (ACF, AlCLF ) was shown to be advantageous in promoting electrophilic [2 + 2] cycloadditions of hexafluoroacetone. ACF, known to be an effective catalyst for the condensation of halomethanes and fluoroolefins " with fluoroethylenes, was also found to catalyze the reaction of HFA with fluoroethylenes. For example, the reaction of HFA and TFE gives the corresponding F-(2,2-dimethyloxetane) 11 in moderate yield along with some polytetrafluoroethylene (Scheme 2.1) ... 

Lewis acids, particularly aluminum chloride, have been noted to catalyze Diels-Alder cycloadditions.The catalytic effect is attributed to coordination of the Lewis acid with the dienophile. The complexed dienophile is then more electron-... 

An enantioselective 1,3-dipolar cycloaddition of nitrones 187 with ethyl vinyl ether 194 catalyzed by Brpnsted acid catalyst 195 was reported by Yamamoto and co-workers. Scheme 3.63 [80]. Only 5 mol% of this air-stable catalyst was used, and the reactions were completed within 1 h. The endo-selectivity of this cycloaddition is different to the previously reported cjto-selectivity of the aluminum-catalyzed reaction (Lewis acid catalysis). 

To avoid some competitive side reactions, Yamamoto recently reported that highly reactive intermediate can be stabilized by the coordination of bulky Lewis acid (Scheme 6.102). That is, bis(2,6-diphenylphenoxide) aluminum triflimide, as a sterically bulky Lewis acid, efficiently catalyzed [2 + 2]cycloaddition of phenyl acrylate with tris(trimethylsilyl)silyl enol ethers to give cycloadducts with high diastereoselectivity [121]. 

As an extension of Miyano s work, Kocienski and coworkers reported that modified aluminum bis(imide) complex (S,S)-(116b) catalyzes [2 + 2]cycloaddition of aldehydes and silylated ketene, which is an easily handled ketene equivalent (Scheme 6.107) [126]. Interestingly, non-C2-symmetrical Lewis acid (S,S)-(116c) was found as an equally effective Lewis acid catalyst. 

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