Diels-Alder reactions aluminum compounds

The mechanism for the hetero-Diels-Alder reaction of benzaldehyde 9 with the very reactive diene, Danishefsky s diene 10, catalyzed by aluminum complexes has been investigated from a theoretical point of view using semi-empirical calculations [27]. The focus in this investigation was to address the question if the reaction proceeds directly to the hetero-Diels-Alder adduct 11, or if 11 is formed via a Mukaiyama aldol intermediate (Scheme 8.4) (see the chapter dealing with hetero-Diels-Alder reactions of carbonyl compounds). 

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... 

The different ratios of 52/53 produced by cycloadditions performed at atmospheric and high pressure, and the forma tion of the unusual trans adducts 53, have been explained by the facts that (i) Diels-Alder reactions under atmospheric pressure are thermodynamically controlled, and (ii) the anti-endo adducts 52 are converted into the short-lived syn-endo adducts 54 which tautomerize (via a dienol or its aluminum complexes) to 53. The formation of trans compounds 53 by induced post-cycloaddition isomerization makes the method more flexible and therefore more useful in organic synthesis. 

Another example of a Bill compound is offered by the ligand VAPOL ( vaulted bisphenanthrol), which combines with AICI3 to form a three-coordinate complex, with no dative interactions. This compound will catalyze Diels-Alder reactions [64]. A five-coordinate compound, with two dative carbonyl bonds attached to the aluminum, has been postulated as the active intermediate in the catalytic reaction. 

These complexes are the first examples of multifunctional catalysts and demonstrate impressively the opportunities that can reside with the as yet hardly investigated bimetallic catalysis. The concept described here is not limited to lanthanides but has been further extended to main group metals such as gallium [31] or aluminum [32]. In addition, this work should be an incentive for the investigation of other metal-binaphthyl complexes to find out whether polynuclear species play a role in catalytic processes there as well. For example, the preparation of ti-tanium-BINOL complexes takes place in the presence of alkali metals [molecular sieve ( )]. A leading contribution in this direction has been made by Kaufmann et al, as early as 1990 [33], It was proven that the reaction of (5)-la with monobromoborane dimethyl sulfide leads exclusively to a binuclear, propeller-like borate compound. This compound was found to catalyze the Diels-Alder reaction of cyclopentadiene and methacrolein with excellent exo-stereoselectivity and enantioselectivity in accordance with the empirical rule for carbonyl compounds which has been presented earlier. 

The earliest report of a reaction mediated by a chiral three coordinate aluminum species describes an asymmetric Meerwein-Poimdorf-Verley reduction of ketones with chiral aluminum alkoxides which resulted in low induction in the alcohol products [1]. Subsequent developments in the area were sparse until over a decade later when chiral aluminum Lewis acids began to be explored in polymerization reactions, with the first report describing the polymerization of benzofuran with catalysts prepared from and ethylaluminum dichloride and a variety of chiral compounds including /5-phenylalanine [2]. Curiously, these reports did not precipitate further studies at the time because the next development in the field did not occur until nearly two decades later when Hashimoto, Komeshima and Koga reported that a catalyst derived from ethylaluminum dichloride and menthol catalyzed the asymmetric Diels-Alder reaction shown in Sch. 1 [3,4]. This is especially curious because the discovery that a Diels-Alder reaction could be accelerated by aluminum chloride was known at the time the polymerization work appeared [5], Perhaps it was because of this long delay, that the report of this asymmetric catalytic Diels-Alder reaction was to become the inspiration for the dramatic increase in activity in this field that we have witnessed in the twenty years since its appearance. It is the intent of this review to present the development of the field of asymmetric catalytic synthesis with chiral aluminum Lewis acids that includes those reports that have appeared in the literature up to the end of 1998. This review will not cover polymerization reactions or supported reactions. The latter will appear in a separate chapter in this handbook. 

Roberson, M., Jepsen, A. S., Jorgensen, K. A. On the mechanism of catalytic enantioselective hetero-Diels-Alder reactions of carbonyl compounds catalyzed by chiral aluminum complexes-a concerted, step-wise or Mukaiyama-aldol pathway. Tetrahedron 2001, 57, 907-913. Monnat, F., Vogel, P., Rayon, V. M., Sordo, J. A. Ab Initio and Experimental Studies on the Hetero-Diels-Alder and Cheletropic Additions of Sulfur Dioxide to (E)-I-Methoxybutadiene A Mechanism Involving Three Molecules of S02. J. Org. Chem. 2002, 67, 1882-1889. 

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. 

Recently, some efficient asymmetric Diels-Alder reactions catalyzed by chiral Lewis acids have been reported [67]. The chiral Lewis acids employed in these reactions are generally based on traditional acids such as titanium, boron, or aluminum reagents, and they are well modified to realize high enantioselectivi-ties. Although lanthanide compounds were expected to be Lewis acid reagents, only a few asymmetric reactions catalyzed by chiral lanthanide Lewis acids were reported. Pioneering work by Danishefsky et al. demonstrated that Eu(hfc)3 (an NMR shift reagent) catalyzed hetero-Diels-Alder reactions of aldehydes with si-loxydienes, but enantiomeric excesses were moderate [68]. 

The original literature preparation of benzazepine 6 (Scheme 3.2) was reported in 1978 by Mazzocchi and Stahly" and began with benzonorbornadiene (3), a compound prepared by the benzyne Diels-Alder reaction of l-bromo-2-fluorobenzene (2) and cyclopentadiene. Mazzocchi and Stahly s preparation involved hydration of the olefin to generate 11 and sequential oxidations of 11 (Al(OtBu)3, Se02, and KO2) that ultimately led to intermediate diacid 13 (see Scheme 3.2). Conversion of 13 to the corresponding anhydride followed by treatment with ammonium hydroxide and thermal dehydration gave cyclic imide 14. Lithium aluminum hydride reduction provided 6 in 2% overall yield. 

Snider, Phillips, and Cordova very cleverly combined two consecutive ene reactions with a formaldehyde Diels-Alder cycloaddition to produce a dihydropyran that has previously been used in a total synthesis of pseudomonic acid (39).54 Thus, 1,5-diene 32 underwent dimethyla-luminum chloride-catalyzed ene reaction with formaldehyde to afford 33 (Scheme 4-XV) as a 8 1 mixture of trans cis isomers (80%). Isomers were not separated since the cis compound did not undergo the subsequent Diels-Alder reaction. Treatment of acetate 34 with ethylaluminum dichloride and formaldehyde in CH2CI2-CH3NO2 (25°C, 12 hr) gave a 37% yield of adduct 38. This transformation presumably involves initial ene reaction of 34 to give 35, which reacted with formaldehyde to produce complex 36. A quasi-intramolecular Diels-Alder cycloaddition then ensued that led to 37. Hydrolysis of aluminum complex 37 gave the desired pyran 38. 

Both enantiomers of binaphthol have found many uses as chiral reagents and catalysts. Thus, they modify reducing agents (e.g., lithium aluminum hydride) for the reduction of ketones to chiral secondary alcohols (Section D.2.3.3.2.) or react with aluminum, titanium or boron compounds to give chiral Lewis acids for asymmetric Diels-Alder reactions (Section D. 1.6.1.1.1.3.) and ene reactions (Section D.I.6.2.). They have also been used as chiral leaving groups in the rearrangement of allyl ethers (Section D.l.1.2.2.) and for the formation of chiral esters with a-oxo acids (Section D. 1.3.1.4.1, and many other purposes. 

The Diels-Alder reaction between 3-(2-nitroethenyl)indole (229) and methyl 3-nitroacrylate (230) in the presence of aluminum chloride in boiling toluene was shown to lead to the formation of both the nitro carbazole species 233 and 235, in very low yield (8%, 1 10), and the corresponding compounds without the nitro group, 234 and 236 (25%, 10 1) [90]. The reaction was presumed to proceed via the cycloaddition adducts 231 and 232 (34%, 3 2), followed by dehydrogenation and denitration (Scheme 51). 

Chiral Catalysts Containing Group 3 (Sc and Y) Metals Including Lanthanides and Actinides. Although lanthanide compounds were expected to be Lewis acid reagents and efficient asymmetric Diels-Alder reactions catalyzed by Lewis acids (containing aluminum and boron) were reported, only few asymmetric Diels-Alder reactions are known. 

In the Diels-Alder reaction of siloxydiene with benzaldehyde in the presence of an organoaluminum compound having an optical active bulky binaphthol as shown in eq. (7.30), the reaction proceeds via the intermediate burst of aluminum coordinated with carbonyl oxygen of benzaldehyde. As the aluminum is bonded with two naphthalene bond with bulky Si(3,5-xylyl)3, the highly stereospecific product is obtained by the restriction of the reaction direction of dienes [44,45,49,49a]. 

In the study of total synthesis of the CP-molecules by Nicolaou group, the asymmetric intramolecular Diels-Alder reaction of prochiral triene compound 44 was conducted under the influence of chiral aluminum Lewis acid catalyst 45, albeit the low level of enantioselectivity (Scheme 34) [58, 59]. 

Significant effects of bis-aluminum Lewis acid catalyst for enantioselective Diels-Alder reactions have been discovered by Yamamoto et al. For example, the asymmetric Diels-Alder reaction of cyclopentadiene and a,(3-unsaturated carbonyl compounds underwent with the aid of chiral bis-aluminum Lewis acid 46 (Scheme 35) [60]. 

Roberson M, Jepsen AS, J0rgensen KA (2001) On the mechanism of catalytic enantioselective hetero-Diels-Alder reactions of carbonyl compounds catalyzed by chiral aluminum complexes—a concerted, step-wise or Mukaiyama-aldol pathway. Tetrahedrrai 57 907—913... 

Some of the developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds have origin in Diels-Alder chemistry, where many of the catalysts have been applied. This is valid for catalysts which enable monodentate coordination of the carbonyl functionality, such as the chiral aluminum and boron complexes. New chiral catalysts for cycloaddition reactions of carbonyl compounds have, however, also been developed. 

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