Heterogeneous Diels-Alder reaction

Pagni, Kabalka et al. have shown that alumina activity deeply affects the diastereoselectivities of the heterogeneous Diels-Alder reactions of cyclopen-tadiene with acrylate esters [Eq. (19), Table 3] [35]. 

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... 

Fraile J. M., Garcia J. I., Mayoral J. A. Heterogeneous Catalysis of Diels-Alder Reactions Recent Res. Dev. Synth. Org. Chem. 1998 1 77-92... 

In the presence of copper perchlorate, the heterogenized catalyst was successfully used for the test Diels-Alder reaction and proved to be similarly active and enantioselective than its homogeneous counterpart. It was further-... 

One-pot synthesis of (E)-2-aryI-1 -cyano-1 -nitroethenes104 and an approach to the synthesis of nitrotetrahydrobenzo[c]chromenones and dihydrodibenzo[b,d]furans were developed based on aqueous Diels-Alder reactions.105 Once again, it was found that the reaction occurred faster in water under heterogeneous conditions relative to those performed in toluene and methylene chloride (Eq. 12.41). 

Some reactions have been found to proceed with better results in the absence of solvent, probably because of the creation of temperature gradients which are eliminated in the presence of a stirred solvent. This was observed for the Diels-Alder reaction of a-amino acid precursors with cyclopentadiene catalyzed by heterogeneous catalysts (Si02-Al, Si02-Ti), when the reaction was performed in toluene or in the absence of solvent [53], Microwave activation increased the rate of reaction without reducing the selectivity of the reaction. 

Another example of the use of Lewis acids in organic reactions in water is the lan-thanide(III) triflate catalysed aza-Diels-Alder reaction, exemplified in Scheme 14. In this reaction the hetero-dienophile is formed in situ from a primary ammonium hydrochloride and a carbonyl compound followed by the actual Diels-Alder reaction288,289. This type of reaction proceeds readily in aqueous media290-296, and a dramatic increase in the yield upon addition of lanthanide triflates was observed288,289. The exact role of the catalyst, however, is not entirely clear. Although it was suggested that the catalyst binds to the dienophile, other mechanisms, such as simple proton catalysis, are also plausible. Moreover, these reactions are further complicated since they are often heterogeneous. 

The chiral (E)-oxazolone derived from 1,2-O-isopropyIidene-D-glyceraldehyde has also been used as a dienophile in the Diels-Alder reaction and, in this case, ( /Z) isomerization of the oxazolone can be avoided using heterogeneous catalysts that promote the synthesis of trans-adducts. ... 

Diels-Alder reactions are thermal reactions requiring no catalysts (120). However, over the years both acid- and metal-based homogeneous or heterogeneous catalysts have been developed (121—127). Some catalysts used in Diels-Alder catalyzed reactions of butadiene are Fe(NO)2Cl—(CH3CH2)2A1C1, Pd[P(C H5)3]4, Cu(I) exchanged silica—alumina (128,129), large pore zeolites (130), and carbon molecular sieves. An electrochemical process has also been used to catalyze the self-condensation to vinylcyclohexene (131). When the asymmetric Ni catalyst (4) was used, specificity to the enantomeric (5)-4-vinylcyclohexene (132,133) was observed (26% enantiomeric excess). 

Diels-Alder reactions.6 The Diels-Alder reaction of cyclopentadiene with dienophiles of the general type CH2=CHR results in endo/exo adducts in the ratio of co. 3 1, and this rcgioselecti vity is not affected by catalysts. The ratio is affected when the reaction is conducted heterogeneously with the dienophile adsorbed on nonactivated surfaces such as A1203, Si02, and cellulose. The most striking effect is shown by methyl acrylate adsorbed on alumina (equation I). 

Chiral oxazoborolidine systems have been regularly used as catalysts for the enantioselective Diels-Alder reaction [173]. Such a catalyst has been immobilized by copolymerization of a sulfonamide-modified styrene monomer to produce polystyrene beads and subsequently reacted with borane to furnish catalyst 49 (Scheme 4.77). A column of 49 was cooled to —30 °C and a 1 1.5 methylacrolein cyclopentadiene solution was flowed in. Following aqueous workup and column chromatography, the desired product 50 was isolated to yield 138 mmol of product in 95% yield and 71% ee by using only 5.7 mmol of catalyst. This result was found to be comparable with the heterogeneous batch reactions that were also attempted [174]. 

It has been observed that enantioselective polymer-bound catalysts prepared by copolymerization produce in some cases better asymmetric inductions than systems prepared by grafting [175]. After much optimization, a monolithic polymer catalyst 51 suitable for a titanium-TADDOLate catalyzed Diels-Alder reaction was developed (Scheme 4.77). The monolith was applied in a flow system both under one pass and 24 h recirculation conditions, the latter producing the best yield (55%) and ee (23%) however, this contrasts poorly with the homogeneous batch reaction although the ee is comparable with the heterogeneous batch process. The reversal of topicity was also... 

Inanaga and co-workers developed another type of lanthanide catalyst for asymmetric hetero Diels-Alder reaction (Sch. 3) [36]. Benzaldehyde reacted with 1-meth-oxy-3-(trimethylsiloxy)-l,3-butadiene in the presence of chiral Yb(III) phosphate to afford the corresponding adduct in 77% yield and in 70% ee. Because the reaction mixture was heterogeneous, they tried to make a clear solution by addition of ligands and examined their effects on the reactions. Pyridine and pyridine derivatives dissolved the catalyst and chemical yields and ee were usually improved. The best result (93% ee) was obtained in the reaction of p-anisaldehyde with 2,6-lutidine as additive. 

During recent years, the homogeneous Lewis acid-catalyzed asymmetric Diels-Alder reactions and hetero-Diels-Alder (HDA) reactions have each undergone extensive study. Various chiral Lewis acids including aluminum, titanium or boron, and chiral ligands such as chiral amino alcohols, diols, salen, bisoxazoline or N-sulfonylamino acids have been used as the catalysts [84]. Much efforts have also been made in the investigation of heterogeneous diastereoselective Diels-Alder reactions. 

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