Lewis acids, catalysts for Diels-Alder reactions

The choice of the best method seems to depend on the catalytic system. A comparison of immobilized catalysts for enantioselective hydrogenation shows a clear superiority of the catalysts that were prepared by grafting. On the other hand, Itsuno [23] found that immobilized Lewis acid catalysts for Diels-Alder reactions showed better performance when they were prepared by copolymerization. 

UI2(BptBu,Me)]-2THF has been described to be an efficient Lewis acid catalyst for Diels-Alder reactions performed in mild conditions and with low amounts of catalysts. The replacement of an iodide in UI3 by a dihydrobispyrazolylborate ligand, however, does not increase activity or selectivity.80... 

First discovered by Otto Paul Hermann Diels and Kurt Alder in 1928, the Diels-Alder reaction involves the cycloaddition of a conjugated diene with substituted alkene (dienophile) to yield a substituted cyclohexene product. These products can be further used in the synthesis of natural products. A lesser-known reaction is the hetero-Diels-Alder (HDA) reaction. In 1974, Danishefsl et al. developed a diene that can easily produce dihydro-pyranones. ° Since then, much research has been performed with Danishefksy s diene in order to develop new Lewis-acid catalysts for Diels-Alder reactions. 

The monocyclopentadienyliron complexes with chiral bidentate phosphorus ligand such as 177 and 178 are suitable Lewis acid catalysts for Diels-Alder reaction of dienes with acryl aldehydes. The reaction proceeds under mild conditions with high yields and ees. In some cases the complex 178 gave better results than 177. Some representative examples of enantioselective Diels-Alder reaction of various acroleins with dienes are given in Table 35 [ 116]. Similar results can be achieved with the ruthenium complexes 179 [117]. 

Catalysis of Diels-Alder Reactions. Et2 AlCl has been extensively used as a Lewis acid catalyst for Diels-Alder reactions. N-Acyloxazolidinones can form both 1 1 (eq 1) and 1 2 complexes with Et2AlCl (eq 2). The 1 2 complex is 100 times as reactive as the 1 1 complex and gives greater endo selectivity and higher de. Me2 AlCl gives similar selectivity with fewer byproducts. 

Catalysis of Diels-Alder Reactions. EtAlCb is a useful Lewis acid catalyst for Diels-Alder reactions. It is reported to be more efficacious for the Diels-Alder reaction of Acrolein and butadiene than either AICI3 or Et2AlCl. It is a useful catalyst for intramolecular Diels-Alder reactions with a,p-unsaturated esters (eq 4) and aldehydes as dienophiles. It has also proven to be a very efficient catalyst for the inter- and intramolecular asymmetric Diels-Alder reaction of chiral a,p-unsaturated acyl sultams (eq 5) and has been used to catalyze a wide variety of Diels-Alder... 

Evans and coworkers262 demonstrated the utility of bis(oxazolidine)copper(II) complexes 425 as Lewis acid catalysts in Diels-Alder reactions of iV-enoyl-l,3-oxazolidin-2-ones 423 with cyclopentadiene, which gave adducts 424 (equation 128, Table 25). Their best results were obtained using catalyst 425c. Surprisingly, only 30% ee was obtained in the reaction between cyclopentadiene and 17a when catalyzed by 425a. Similar results were obtained for the thiazolidine-2-thione analogs of the iV-enoyl-l,3-oxazolidin-2-ones. 

Chiral Lewis Acid. These chiral titanium reagents are widely used as chiral Lewis acid catalysts. The Diels-Alder reaction of methyl acrylate and cyclopentadiene affords the endo adduct in moderate enantioselectivity when a stoichiometric amount of the chiral titanium reagent (5) is employed (eq 6). Use of 3-(2-alkenoyl)-l,3-oxazolidin-2-ones as dienophiles greatly improves the optical purity of the cycloadduct when the 2-phenyl-2-methyl-1,3-dioxolane derivative (6) is used as a chiral ligand. Most importantly, the reaction proceeds with the same high enantioselectivity for the combination of various dienophiles and dienes even when 5-10 mol % of the chiral titanium reagent is employed in the presence of molecular sieves 4A (eqs 7 and 8). ... 

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

Chloroaluminate ionic liquids (typically a mixture of a quaternary ammonium salt with aluminum chloride see Table 6.9) exhibit at room temperature variable Lewis acidity and have been successfully used as solvent/catalyst for Diels-Alder reactions [57]. The composition of chloroaluminate ionic liquids can vary from basic ([FMIM]C1 or [BP]C1 in excess) to acidic (AICI3 in excess) and this fact can be used to affect the reactivity and selectivity of the reaction. The reaction of cyclopentadiene with methyl acrylate is an example (Scheme 6.31). 

Recently, this concept could be transferred to the homologous silylium ions 3-Si (Si in cx-position to the ferrocene core) [18, 19], which were found to be potent catalysts for Diels-Alder reactions at low temperature [19]. The electron-rich ferrocene core buffers the Lewis acidity, thus avoiding the irreversible formation of Lewis pairs. 

Microwave heating has also been employed for performing retro-Diels-Alder cycloaddition reactions, as exemplified in Scheme 6.94. In the context of preparing optically pure cross-conjugated cydopentadienones as precursors to arachidonic acid derivatives, Evans, Eddolls, and coworkers performed microwave-mediated Lewis acid-catalyzed retro-Diels-Alder reactions of suitable exo-cyclic enone building blocks [193, 194], The microwave-mediated transformations were performed in dichloromethane at 60-100 °C with 0.5 equivalents of methylaluminum dichloride as catalyst and 5 equivalents of maleic anhydride as cyclopentadiene trap. In most cases, the reaction was stopped after 30 min since continued irradiation eroded the product yields. The use of short bursts of microwave irradiation minimized doublebond isomerization. 

Taguchi and coworkers175 studied the Lewis acid catalyzed asymmetric Diels-Alder reactions of chiral 2-fluoroacrylic acid derivatives with isoprene and cyclopentadiene. When a chiral l,3-oxazolidin-2-one and diethylaluminum chloride were used as the chiral auxiliary and the Lewis acid catalyst, respectively, a de of 90% was observed for the reaction with isoprene. The reaction with cyclopentadiene afforded a 1 1 mixture of endo and exo isomers with de values of 95% and 96%, respectively. The endo/exo selectivity was improved by using 8-phenylmenthol as the chiral auxiliary. Thus, the reaction... 

An extensive review of the use of chiral Lewis acid catalysts in Diels-Alder cycloadditions has been presented. Brpnsted acid-assisted chiral Lewis acids have been shown to be highly efficient catalysts for the enantioselective Diels-Alder reactions of a- and /3-substituted-Q, /i-enals with numerous dienes. The chiral Lewis acid-catalysed Diels-Alder reaction between cyclopentadiene and alkenoyloxazolidi-nones can be catalysed by bis(oxazolone)magnesium catalysts. ... 

There is the potential with some substrates that the Lewis acidity of the lanthanide ion can catalyze a reaction. For example, the addition of Eu(hfc)3 to a racemic mixture of dimethylpenta-2,3-dienoates (39) caused an enrichment of the (5 )-isomer °. Over nine days the mixture converted to an 89 11 mixture. Lanthanide tris( S-diketonates) are well known catalysts for Diels-Alder reactions, and NMR spectroscopy of the reactants with Eu(hfc)3 was used to understand the stereoselectivity of the europium-catalyzed cycloadditions . ... 

The complexes are isolated, characterized and used as chiral Lewis acids. Dissociation of the labile ligand liberates a single coordination site at the metal center. These Lewis acids catalyze enantioselective Diels-Alder reactions. For instance, reaction of methacrolein with cyclopentadiene in the presence of the cationic iron complex (L = acrolein) occurs with exo selectivity and an enantiomeric excess of the same order of magnitude as those obtained with the successful boron and copper catalysts (eq 3). ... 

The copper catalyzed Diels-Alder reactions of a variety of dienes have been elegantly exploited by Evans as a key step in the synthesis of natural products (Sch. 49). The synthesis of tetrahydrocannabinol (219) [92] employs the acyclic diene 217 furan is used as a diene in the synthesis of shikimic acid (222) [93]. Although the methodology uses the very reactive catalyst 188, the reactions are still slow, suggesting that less reactive dienes require longer reaction times and higher temperatures for completion. A copper Lewis acid-mediated intramolecular Diels-Alder reaction has served as a key step in the total synthesis of isopulo upone [94]. 

In most Diels-Alder reactions, no catalyst is needed, but Lewis acids are effective catalysts in many cases, particularly those in which Z in the dienophile is a C=0 or C=N group. A Lewis acid catalyst usually increases both the regioselec-tivity of the reaction (in the sense given above) and the extent of endo addition, °° and, in the case of enantioselective reactions, the extent of enantioselectivity. It has been shown that InCla is an effective catalyst for aqueous Diels-Alder reactions,which is suitable for ionic Diels-Alder reactions, and there are other Lewis acid catalysts that are effective in water. °° Brpnsted acids have also been used to accelerate the rate of the Diels-Alder reaction.Lanthanum triflate [La(OTf)3] has been reported as a reusable catalyst ° ° and Me3SiNTf2 has been used as a green Lewis acid catalyst. ° Cationic Diels-Alder catalysts have been developed, particularly oxazaborolidine catalysts. ° Some Diels-Alder reactions can also be catalyzed by the addition of a stable cation radical, for... 

The novel chiral Lewis acid (49) is an excellent catalyst for Diels-Alder reactions. The rran5-4,5-diaryl-l,3-bistriflyl-l,3,2-diazaluminolidines (50A) have been exploited in the elaboration of a chiral tetrahydrophthahmide intermediate for the synthesis of gracillin-B and gracillin-C. ... 

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