Scandium Diels-Alder reactions

It turned out that the dodecylsulfate surfactants Co(DS)i Ni(DS)2, Cu(DS)2 and Zn(DS)2 containing catalytically active counterions are extremely potent catalysts for the Diels-Alder reaction between 5.1 and 5.2 (see Scheme 5.1). The physical properties of these micelles have been described in the literature and a small number of catalytic studies have been reported. The influence of Cu(DS)2 micelles on the kinetics of quenching of a photoexcited species has been investigated. Interestingly, Kobayashi recently employed surfactants in scandium triflate catalysed aldol reactions". Robinson et al. have demonshuted that the interaction between metal ions and ligand at the surface of dodecylsulfate micelles can be extremely efficient. ... 

Scandium(lll) perfluorooctanesulfonate [Sc(OPf)3 a novel catalyst for the hetero-Diels-Alder reaction of aldehydes with non-activated dienes [108]... 

Scandium trifluoromethansulfonate (Sc(OTf)3). A novel reusable catalyst in the Diels-Alder reaction [108]... 

Fukuzawa et al. [99] found analogous scandium(III)triflate/ Pr-PyBOx complex as efficient catalyst for the asymmetric Diels-Alder reaction between cyclopentadiene or acyclic dienes and acyl-l,3-oxazohdin-2-ones with up to 90% ee. They latter described the same reaction in super critical CO2 in the presence of MSdA [ 100] that proceeded more rapidly than in CH2CI2 leading to the expected product with analogous selectivity. 

Scott Oakes et al. (1999a, b) have shown how adoption of SC conditions can lead to a dramatic pressure-dependent enhancement of diastereoselectivity. In the case of sulphoxidation of cysteine derivatives with rert-butyl hydroperoxide, with cationic ion-exchange resin Amberlyst-15 as a catalyst, 95% de was realized at 40 °C and with SC CO2. By contrast, with conventional solvents no distereoselectivity was observed. Another example is the Diels-Alder reaction of acrylates with cyclopentadiene in SC CO2 at 50 °C, with scandium tris (trifluoromethanesulphonate) as a Lewis acid catalyst. The endoiexo ratio of the product was as high as 24 1, while in a solvent like toluene it was only 10 1. 

Kobayashi has found that scandium triflate, Sc(OTf)3,36 and lanthanide triflate, Ln(OTf)3, are stable and can be used as Lewis catalysts under aqueous conditions. Many other Lewis acids have also been reported to catalyze Diels-Alder reactions in aqueous media. For example, Engberts reported37 that the cyclization reaction in Eq. 12.7 in an aqueous solution containing 0.010 M Cu(N03)2 is 250,000 times faster than that in acetonitrile and about 1,000 times faster than that in water alone. Other salts, such as Co2+, Ni2+, and Zn2+, also catalyze the reaction, but not as effectively as Cu2+. However, water has no effect on the endo-exo selectivity for the Lewis-acid catalyzed reaction. 

The advantages of using ionic liquids as solvents for Diels-Alder reactions are exemplified by the scandium triflate catalysed reactions [14] in [bmim][PFg], [bmim][SbF6] and [bmim][OTf] for the reaction shown in Scheme 7.6. Whilst the nature of the anion seems to have little effect, all these solvents give rate enhancements for a range of Diels-Alder reactions compared to when the reactions are carried out in dichloromethane (DCM). Also, the selectivity towards the endo product is higher than in conventional solvents. As well as the enhanced rates and selectivities, the products can also be removed by extraction with diethyl ether and the ionic liquid and catalyst can immediately be reused. Experiments... 

Although the above demonstrated that product control could be achieved in scC02, the difference in selectivity was relatively small. However, later work using a Lewis acid catalyst, scandium triflate, on the Diels-Alder reaction of n-butyl acrylate and cyclopentadiene (Scheme 7.7) showed that the endo exo ratio was again found to rise to a maximum and then decrease again as the pressure, and hence density, was increased (Figure 7.3) [19]. 

To date, reports have involved palladium catalysts for Suzuki and Sono-gashira coupling reactions [63-66], rhodium catalysts for silylations of alcohols by trialkylsilanes [67,68], and tin-, hafnium-, and scandium-based Lewis acid catalysts for Baeyer-Villiger and Diels-Alder reactions [69]. Regardless of exact mechanism, this recovery strategy represents an important direction for future research and applications development. Finally, a particularly elegant protocol where CO2 pressure is used instead of temperature to desorb a fluorous rhodium hydrogenation catalyst from fluorous silica gel deserves emphasis [28]. 

Fig. 13). The cross-linked scandium-modified dendrimer was tested in a number of Lewis acid-catalyzed reactions, including Mukaiyama aldol additions to aldehydes and aldimines, Diels-Alder reactions, and Friedel-Crafts acylations. The dendritic catalyst was recovered by a simple filtration. The Mukaiyama aldol... 

In the Mukaiyama aldol additions of trimethyl-(l-phenyl-propenyloxy)-silane to give benzaldehyde and cinnamaldehyde catalyzed by 7 mol% supported scandium catalyst, a 1 1 mixture of diastereomers was obtained. Again, the dendritic catalyst could be recycled easily without any loss in performance. The scandium cross-linked dendritic material appeared to be an efficient catalyst for the Diels-Alder reaction between methyl vinyl ketone and cyclopentadiene. The Diels-Alder adduct was formed in dichloromethane at 0°C in 79% yield with an endo/exo ratio of 85 15. The material was also used as a Friedel-Crafts acylation catalyst (contain-ing7mol% scandium) for the formation of / -methoxyacetophenone (in a 73% yield) from anisole, acetic acid anhydride, and lithium perchlorate at 50°C in nitromethane. 

A series of trivalent lanthanoid complexes, scandium, and ytterbium tris-(R)-(-)-1,1 -binaphthyl-2,2 -diyl phosphonate, have been introduced as new chiral and stable Lewis acids for the asymmetric hetero Diels-Alder reaction of Danishefsky s diene and aldehydes. 2,6-Lutidine was found to be an effective additive to improve the enantioselectivity up to 89% ee [66] (Eq. 8A.42). 

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. 

Scheme 9.25 Scandium catalysed Diels-Alder reaction...

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. 

Table 3. Enantioselective Diels-Alder reactions with a chiral scandium catalyst,...

Although asymmetric versions of aza Diels-Alder reactions using chiral auxiliaries have been reported, only one example uses a stoichiometric amount of a chiral Lewis acid [44]. The first reported example of a catalytic enantioselective aza Diels-Alder reaction employed a chiral lanthanide catalyst [45]. A chiral ytterbium or scandium catalyst, prepared from Yb(OTf)3 or Sc(OTf)3, (i )-BINOL, and DBU, is effective in the enantioselective aza Diels-Alder reactions. The reaction of A-alkylidene- or N-arylidene-2-hydroxyaniline with cyclopentadiene proceeded in the presence of the chiral catalyst and 2,6-di-rerf-butyl-4-methylpyridine (DTBMP) to afford the corresponding 8-hydroxyquinoline derivatives in good to high yields with good to excellent diastereo- and enantioselectivity (Eq. 15). 

Catalytic asymmetric 1,3-dipolar cycloaddition of a nitrone with a dipolarophile has been performed using a chiral scandium catalyst [31]. The chiral catalyst, which was effective in asymmetric Diels-Alder reactions, was readily prepared from Sc(OTf)3, (7 )-(-i-)-BINOL, and d5 -l,2,6-trimethylpiperidine. The reaction of benzylbenzylide-neamine A-oxide with 3-(2-butenoyl)-l,3-oxazolidin-2-one was performed in the presence of the chiral catalyst to yield the desired isoxazolidine in 69 % ee with perfect diastereoselectivity (endolexo = > 99 1) (Sch. 8) [31,46], It was found that reverse enantioselectivity was observed when a chiral Yb catalyst, prepared from Yb(OTf)3, the same (i )-(-i-)-BINOL, and cd-l,2,6-trimethylpiperidine, was used instead of the Sc catalyst under the same reaction conditions. 

Rare earth metal triflates are recognized as a very efficient Lewis acid catalysts of several reactions including the aldol reaction, the Michael reaction, allylation, the Diels-Alder reaction, the Friedel-Crafts reaction, and glycosylation [110]. A polymer-sup-ported scandium catalyst has been developed and used for quinoline library synthesis (Sch. 8) [111], because lanthanide triflates were known to be effective in the synthesis of quinolines from A-arylimines [112,113]. This catalyst (103) was readily prepared from poly(acrylonitrile) 100 by chemical modification. A variety of combinations of aldehydes, amines, and olefins are possible in this reaction. Use of the polymer-supported catalyst has several advantages in quinoline library construction. 

Structural homolog. Scandium(III) perfluorooctanesulfonate has been used to catalyze the hetero-Diels-Alder reaction of nonactivated dienes and aldehydes to form 27/-pyrans. 

Simple imines undergo Diels-Alder reactions in the presence of suitable catalysts. Lanthanide triflates, which are stable in water, are especially effective. Thus in the presence of 10 mol% of ytterbium or scandium triflate, Danishefsky s diene 4 reacts with benzylideneaniline in acetonitrile at 0 °C to give the dihydropyridone 76 quantitatively (equation 50) analogous products are obtained from 4 and furylideneaniline, benzyli-denebenzylamine and pentyIidenebenzylamine. In a one-pot version of the reaction, a mixture of an aldehyde, an amine and the diene 4 in acetonitrile containing magnesium sulfate is treated with 10 mol% ytterbium triflate to afford the dihydropyridone in ca 80% yield. Even phenylglyoxal monohydrate can be employed. ... 

In another attempt. Song et al. reported that ionic liquids [bmim]PF act as powerful media in scandium triflate catalyzed Diels-Alder reactions not only for the facilitating of catalyst recovery but also for the accelerating of the reaction rate and improving of selectivity (Scheme 17.5). Various dienes and dienophiles provided excellent yields and selectivity at room temperature in 4 h [47]. 

Scheme 17.5 Scandium triflate catalyzed Diels-Alder reaction under [bmim]PF ...

Song CE, Shim WH, Roh El, Lee S, Choi JH (2001) Ionic liquids as powerful media in scandium triflate catalyzed Diels-Alder reactions signiflcant rate acceleration, selectivity improvement and easy recycling of catalyst. Chem Commun 1122-1123... 

Methylrhenium trioxide (CH3Re03) has proved to be an excellent catalyst in organic solvents, and in water when the dienophile is an a, -unsaturated ketone (or aldehyde). Nearly exclusively one product isomer was formed, the same one that usually predominates [47]. Likewise, scandium triflate [48] and indium trichloride [49] were found to catalyze the Diels-Alder reaction in a tetrahydro-furan/water mixture and in pure water, respectively. 

---