Lanthanide complexes Diels-Alder reaction catalysts

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. 

Perhaps the most attractive method of introducing enantioselectivity into the Diels-Alder reaction is to use a chiral catalyst in the form of a Lewis acidic metal complex. In recent years, this area has shown the greatest progress, with the introduction of many excellent catalytic processes. Quite a number of ligand-metal combinations have been evaluated for their potential as chiral catalysts in Diels-Alder reactions. The most commonly used metals are boron, titanium, and aluminum. Copper, magnesium, and lanthanides have also been used in asymmetric catalytic Diels-Alder reactions. 

In the presence of a catalytic amount of chiral lanthanide triflate 63, the reaction of 3-acyl-l,3-oxazolidin-2-ones with cyclopentadiene produces Diels-Alder adducts in high yields and high ee. The chiral lanthanide triflate 63 can be prepared from ytterbium triflate, (R)-( I )-binaphthol, and a tertiary amine. Both enantiomers of the cycloaddition product can be prepared via this chiral lanthanide (III) complex-catalyzed reaction using the same chiral source [(R)-(+)-binaphthol] and an appropriately selected achiral ligand. This achiral ligand serves as an additive to stabilize the catalyst in the sense of preventing the catalyst from aging. Asymmetric catalytic aza Diels-Alder reactions can also be carried out successfully under these conditions (Scheme 5-21).19... 

Kobayashi reported an asymmetric Diels-Alder reaction catalyzed by a chiral lanthanide(III) complex 24, prepared from ytterbium or scandium triflate [ Yb(OTf)3 or Sc(OTf)3], (Zf)-BINOL and tertiary amine (ex. 1,2,6-trimethylpiperidine) [30], A highly enantioselective and endose-lective Diels-Alder reaction of 3-(2-butenoyl)-l,3-oxazolidin-2-one (23) with cyclopentadiene (Scheme 9.13) takes place in the presence of 24. When chiral Sc catalyst 24a was used, asymmetric amplification was observed with regard to the enantiopurity of (/ )-BINOL and that of the endoadduct [31 ]. On the other hand, in the case of chiral Yb catalyst 24b, NLE was affected by additives, that is, when 3-acetyl-l,3-oxazolidin-2-one was added, almost no deviation was observed from linearity, whereas a negative NLE was observed with the addition of 3-pheny-lacetylacetone. 

Diels-Alder catalysts.1 These lanthanide complexes markedly improve the rate and endo-selectivity of Diels-Alder reactions of cyclopentadiene with allenic... 

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. 

Lanthanide triflates catalyse Diels-Alder reactions, with the scandium complex as the most effective catalyst, and, again, the catalyst can be recovered and reused, being just as effective in subsequent runs. 

Lanthanide Lewis acids catalyze many of the reactions catalyzed by other Lewis acids, for example, the Mukaiyama-aldol reaction [14], Diels-Alder reactions [15], epoxide opening by TMSCN and thiols [14,10], and the cyanosilylation of aldehydes and ketones [17]. For most of these reactions, however, lanthanide Lewis acids have no advantages over other Lewis acids. The enantioselective hetero Diels-Alder reactions reported by Danishefsky et al. exploited one of the characteristic properties of lanthanides—mild Lewis acidity. This mildness enables the use of substrates unstable to common Lewis acids, for example Danishefsky s diene. It was recently reported by Shull and Koreeda that Eu(fod)3 catalyzed the allylic 1,3-transposition of methoxyace-tates (Table 7) [18]. This rearrangement did not proceed with acetates or benzoates, and seemed selective to a-alkoxyacetates. This suggested that the methoxy group could act as an additional coordination site for the Eu catalyst, and that this stabilized the complex of the Eu catalyst and the ester. The reaction proceeded even when the substrate contained an alkynyl group (entry 7), or when proximal alkenyl carbons of the allylic acetate were fully substituted (entries 10, 11 and 13). In these cases, the Pd(II) catalyzed allylic 1,3-transposition of allylic acetates was not efficient. 

Danishefsky and co-workers pioneered the use of chiral lanthanide complexes as catalysts in organic reactions. They found out that Eu(hfc)3, which is used as an NMR shift reagent, promoted hetero Diels-Alder reactions [30] of aldehydes with siloxydienes and induced enantiomeric enrichment (Sch. 1) [31]. Suitable substituents on the dienes were introduced to improve the extent of asymmetric induction. The best result was obtained in the reaction of benzaldehyde with l-methoxy-2-methyl-3-(trimethyl-siloxy)- , 3-butadiene using 1 mol % Eu(hfc)3 the enantiomerie excess was, however, moderate (58%). The authors maintained that the major advantage of lanthanide catalysis lay in the survival of otherwise labile systems used as adducts. 

L-Iduronyl synthons catalyzed by a vinyl cerium reagent have been shown to open a way to an efficient preparation of l,2,4-tri-0-acetyl-3-0-benzyl-Z,-iduronyl derivatives.1097 The synthetic utility of the cationic lanthanide complex [Cp 2Ce][BPh4] as an effective Lewis acid catalyst for the hetero-Diels-Alder reaction between Danishefsky s diene and substituted benzaldehydes has been demonstrated (Scheme 307). 

Many researchers have refrained from using lanthanide complexes in stereoselective Diels-Alder reactions, perhaps due to large coordination spheres which can accommodate up to a dozen ligands. The rather daunting task of interpreting the identity of active catalysts and substrate-catalyst complexes among the myriad possible options has not hampered the development of some quite useful chiral lanthanide catalysts. 

Mikami and coworkers also reported the development of lanthanide bis(trif-luoromethanesulfonyl)amides (bistrifylamides) as a new type of asymmetric catalysts for the hetero-Diels-Alder reaction of Danishefsky s diene, wherein the significant effect of water as an additive is observed in increasing not only the enan-tioselectivity but also the chemical yield. Bistrifylamides can be used as effective bidentate Hgands to increase the Lewis acidity of their chiral metal complexes on account of the higher acidity of the conjugated acids than those of afiphatic and aromatic diols, which are commonly used as chiral bidentate hgands [33]. 

The Lewis acidity of lanthanide complexes has been known for a long time. It was exploited extensively in their use as NMR shift reagents, mainly Eu(fod)3. They show strong affinity toward carbonyl oxygens and, therefore, have been widely used as catalysts for cycloaddition of dienes with aldehydes [25]. Moreover, the ability of catalytic amounts of lanthanide compoimds to activate coordinating nitriles as well as imines has also been recognized [26]. In recent years lanthanide (III) complexes have demonstrated clear effectiveness in catalyzing not only hetero-Diels-Alder reactions, but also Michael, aldol, Strecker and Friedel-Crafts acylation reactions [27]. 

Further examples also show particularly impressive selectivity. Kiindig has used the cationic iron catalyst (8.83) in the Diels-Alder reaction to give cycloadduct (8.85). The ruthenium (BINAP) catalyst (8.86) effects the Diels-Alder reaction of cyclopentadiene with 2-substituted acrylates with ees up to 99%. Kobayashi has shown that lanthanide and scandium triflate complexes of BINOL with 1,2,6-trimethylpiperidine, formulated as complex (8.87), are effective with oxazohdinone-based substratesand gives good selectivity in the formation of the Diels-Alder product (8.52). 

A comparative study on the influence of different lanthanide cations and the substituents at the 4 and 5 -positions in the pybox ligands in the Diels-Alder reaction of cyclopentadiene with 3-acryloyl-l,3-oxazolidin-2-one was realized [135], Of the catalysts derived from (4 P,5 P)-4-Me-5-Ph-pybox, the Sc(III)-based one is both strongly endo selective (endo/exo = 97/3) and highly enantioselective (97% ee (endo)). Later, it was found that the scandium-(4 S,5 S)-4-CH20TIPS-5-Ph-pybox complex also gave endo selective (endo/exo = 92/8-96/4) and highly enantioselective (93-99% ee (endo)) for the Diels-Alder reactions of cyclopentadiene with 3-acryloyl-or 3-crotonoyloxazolidinones. 

Danishefsky and coworkers pioneered the use of chiral lanthanide complexes as catalysts in organic reactions. They found out that Eu(hfc)3, which is known as a NMR shift reagent, promoted hetero Diels-Alder reactions of aldehydes with siloxydienes and induced enantiomeric enrichment (Scheme 13.19). The best result was obtained... 

Inanaga and coworkers developed another type of lanthanide catalysts for asymmetric hetero Diels-Alder reaction (Scheme 13.23) [59, 60]. Benzaldehyde reacted with l-methoxy-3-(trimethylsiloxy)-l,3-butadiene in the presence of chiral Yb(III) phosphate complex, Yb[(R)-BNP]3, to afford the corresponding adduct with 77% yield and 70% ee. 2,6-Lutidine worked best as achiral additive in the system to improve reactivity as well as enantioselectivity (89% ee) [59b]. In modification studies of the chiral ligand to improve solubility and chiral environment of catalyst, partially reduced (R)-Hg-BNP was found more suitable than original (R)-BNP ligand in this reaction. Yb[(R)-H8-BNP]3 complex promoted the reaction in 98% ee (R=Ph) without any additives (Scheme 13.23a) [59c]. Yb[(P)-BNP]3 complex was... 

Kobayashi and coworkers revealed that lanthanide triflates were excellent catalysts for aza-Diels-Alder reactions, and they successfully extended these into enantios-elective variants [65]. Initial trials using N-benzylideneaniline and cyclopentadiene with Yb(OTf)3 /B INOL/amine base system, which was optimized for Diels-Alder reaction (Scheme 13.20) resulted in failure. On the basis of the assumption that biden-tate substrate would be more suitable, N-benzylidene-2-hydroxyaniline was used for optimization studies. In the aza-Diels-Alder reaction, Yb(OTf)3/BINOL/DBU complex with 1 equivof amine additive afforded the best enantioselectivity (Table 13.21). 

The use of lanthanide complexes in asymmetric catalysis was pioneered by Danishefsky s group with the hetero-Diels-Alder reaction,and their utility as chiral Lewis acid catalysts was shown by Kobayashi. The Brpnsted base character of lanthanide-alkoxides has been used by Shibasaki for aldol reactions, cyanosilylation of aldehydes and nitroaldol reactions.The combination of Lewis acid and Brpnsted base properties of lanthanide complexes has been exploited in particular by Shibasaki for bifunctional asymmetric catalysis. These bimetallic lanthanide-main-group BINOL complexes are synthesized according to the following routes ... 

The synthetic utihty of the cationic lanthanide complex [Cp 2Ce][BPh4] as a Lewis acid catalyst, effective with as little as 0.1% loading, for the Diels Alder reaction between Danishefsky s diene and aromatic aldehydes has been demon-strated. s-Caprolactone can be prepared by H2O2 oxidation of cyclohexanone in the presence of catalysts of the type Ln[(02SR) X] (R = perfluoroalkyl n, X = 1,0 2, N 3, Reaction of oxime esters with MejSiCN under the influence of a catalytic amount of La(OPr )3 was found to produce ot-trimethylsilyl oxy-dinitrile derivatives in good yields. ... 

Lanthanide /3-diketonates have been used as catalysts in Diels-Alder reactions. The first example of a lanthanide-catalyzed cycloaddition was the dimerization of spiro[2.4]hepta-4,6-diene by [Eu(tfn)3] (Morrill et al., 1975) (scheme 2). In the absence of the europiitm(lll) complex no dimerization took place. Because of the mild experimental conditions, this catalyst has potential in Diels-Alder reactions where acid labile components are combined. An example is the cycloaddition of cyclopentadiene with acrolein (Danishefsky and Bednarski, 1985). 

Mechanistically, the cycloaddition reaction is rather complex. Depending on the catalyst or solvent used and the reaction substrates, pericyclic and/or Mukaiyama aldol-like pathways may be involved.43 The pericyclic mechanism, generally favored by zinc chloride and the lanthanide catalysts, tends to produce adducts having the cis relative stereochemistry at C-5,6. It is assumed that chelation of the aldehyde with the Lewis acid occurs in an anti fashion and that the steric bulk of R is less than that of the Lewis acid-solvent complex L [Eq. (11)], thus favoring a Diels-Alder transition state with R endo. 

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