Michael scandium catalysts

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. 

Highly enantioselective Michael reactions of indanone and tetralone -ketoesters derivatives with a,P-unsaturated ketones promoted by a chiral scandium catalyst have been developed [123]. In the presence of Sc(OTf)3 and bipyridine (3), the reactions proceeded smoothly in dichloroethane at 40 °C to give the corresponding adducts in moderate to excellent yields with excellent enantioselectivities in most cases (Scheme 12.47). It was found that a lower concentration of the reaction mixture was key to attaining high selectivity. 

In the very recent past, metal complex catalysis has been used with advantage for the stereo- and enantio selective syntheses based on the Henry and Michael reactions with SENAs (454-458). The characteristic features of these transformations can be exemplified by catalysis of the reactions of SENAs (327) with functionalized imides (328) by ligated trivalent scandium complexes or mono-and divalent copper complexes (454) (Scheme 3.192). Apparently, the catalyst initially forms a complex with imide (328), which reacts with nitronate (327) to give the key intermediate A. Evidently, diastereo- and enantioselectivity of the process are associated with preferable transformations of this intermediate. 

In recent years, many chiral catalysts for the enantioselective synthesis of optical active 1,5-dicarbonyl compounds have been developed, such as chiral crown ethers with potassium salt bases and chiral palladium complexes, including bimetallic systems. Nakajima and coworkers reported on enantioselective Michael reactions of S-keto esters to a,/3-unsaturated carbonyl compounds in the presence of a chiral biquinoline N,N dioxide-scandium complex, which catalyzed the additions in high yields and with enan-tioselectivities up to 84% ee . Kobayashi and coworkers found that the combination of Sc(OTf)3 with the chiral bipyridine ligand 149 (equation 41) was also effective as a chiral catalyst for asymmetric Michael additions of 1,3-dicarbonyl compounds 147 to a,/3-unsaturated ketones 148. The corresponding Michael adducts 150 were obtained in good to high yields with excellent enantiomeric excesses in most cases (Table 10). 

The catalytic asymmetric Michael reaction using silyl enol esters (Mukaiyama-Michael reaction) as the pronucleophiles has been reported using a titanium/BINOL catalyst (in up to 90% ee). Considering furan (11.36) as a silyl enol ether, this has been shown to undergo nucleophilic addition to the Michael acceptor (11.37). The product (11.38) canbe obtained with excellent diastereocon-trol with the scandium complex of hgand (11.39), or with excellent enantiocontrol... 

Kobayashi and coworkers further developed a new immobilizing technique for metal catalysts, a PI method [58-61]. They originally used the technique for palladium catalysts, and then applied it to Lewis acids. The PI method was successfully used for the preparation of immobilized Sc(OTf)3. When copolymer (122) was used for the microencapsulation of Sc(OTf)3, remarkable solvent effects were observed. Random aggregation of copolymer (122)-Sc(OTf)3 was obtained in toluene, which was named as polymer incarcerated (PI) Sc(OTf)3. On the other hand, spherical micelles were formed in THF-cyclohexane, which was named polymer-micelle incarcerated (PMI) Sc(OTf)3.. PMI Sc(OTf)3 worked well in the Mukaiyama-aldol reaction of benzaldehyde with (123) and showed higher catalytic activity compared to that of PI Sc(OTf)3 mainly due to its larger surface area of PMI Sc(OTf)3. This catalyst was also used in other reactions such as Mannich-type (123) and (125) and Michael (127) and (128) reactions. For Michael reactions, inorganic support such as montmorilonite-enwrapped Scandium is also an efficient catalyst [62]. 

A hydrophobic polymer-supported scandium(III) catalyst was also successfully used in the Michael reaction of unsaturated ketones with silyl enol ethers. Recently, an amphiphilic resin-supported rhodium/phosphine complex was used as catalyst in the 1,4-addition of various boronic acids to enones in water at 25°C. High yields were obtained and the catalyst was easily separated and subjected to a second and third round of reactions with no decrease in activity. ... 

The first Lewis acid-catalyzed asymmetric Michael addition in water was developed by Kobayashi et al, who reported ee s up to 83%. Very recent developments show great promise for further improvement of Michael addition reactions in water. In an elegant study, Kaneda and coworkers used montmorillonite-enwrapped metal triflates to execute C—C bond forming Michael additions. When scandium triflate was employed, adducts were obtained in quantitative yield within a 0.5-3 h at or slightly above room temperature. The catalysts were reusable with no appreciable loss in activity.In another recent study, Lind-strdm and coworkers observed a remarkable ligand acceleration effect in aqueous ytterbium triflate-catalyzed Michael additions. A number of 1,2-diamines and 1,2-aminoalcohols were shown to have a positive influence on the rate of the reaction, the most efficient being tetramethylethylenediamine, which induced a nearly 20-fold rate acceleration. 

Friedel-Craft Alkylation Conjugated Additions. In the last decade, several methodologies have been developed to enantios-electively alkylate the Al-methylindole via a conjugated addition. One of them uses an a./S-unsaturated acylphosphonate as electrophile and a scandium(III) PyBox as chiral catalyst. After the Michael addition, the phosphonate moiety is directly converted into an ester by adding the corresponding alcohol in the presence of DBU. The desired product is isolated in 88% yield and 98% ee (eq... 

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