Scandium immobilization

The other direction concerns the use of immobilized transition metal catalysts in the synthesis of libraries of organic compounds of interest in therapeutic drug discovery. One such strategy uses immobilized catalysts (e.g., scandium complexes), leading to efficient library syntheses of quinolines, amino ketones, and amino acid esters.72,73... 

Yadav, J.S., Reddy, B.V.S., Gayathri, K.U. and Prasad, A.R. (2002) Scandium triflate immobilized in ionic liquids A novel and recyclable catalytic system for hetero-Diels-Alder reactions. Synthesis-Stuttgart, 17, 2537-2541. 

Scandium tris(perfluorooctanesulfonyl)methide complex was immobilized in a fluorous phase as a recyclable catalyst for Mukaiyama aldol reaction (2). On the other hand, the catalytic activity of scandium could be significantly increased by the use of a continuous flow system compared with a batch system. For example, in per-fluoromethylcyclohexane, the aldol reaction of benzaldehyde withthe trimethylsilyl enol ether derived from methyl 2-methylpropannoate was completed within seconds in the presence of less than 0.1 mol% of Sc(N(S02CgFi7)2]3 [3]. 

Based on Mannich-type reactions of N-acryliminoacetates with silyl enol ethers, a new method for the preparation of N-acylated amino acid derivatives via nucleophilic addition to N-acrylimino ester has been developed using a polymer-supported amine and scandium catalysts (Scheme 12.5) [9]. Ethyl N-benzoyl-2-bromoglycine was used as a substrate. It could be readily converted to reactive N-acrylimino ester in situ by treatment with a base. Immobilizations of the amine and the scandium species into polymeric supports prevented loss of activity of the catalyst. The method is simple and provides a convenient method for the preparation of N-acrylated amino acid derivatives. 

Diels-Alder reactions are one of the most important classes of cycloaddition reactions. They are, however, commonly associated with moisture-sensitive Lewis acids, such as AICI4, TiCU, and SnCU. Scandium salts are known as powerful catalysts for many types of Diels-Alder reactions [23, 24]. Recent advances have been focused on immobilization of Sc catalysts to explore new reactions. 

Since the discovery of Sc(OTf)3 as a water-compatible Lewis acid, several immobilized scandium catalysts that work efficiently in water have been developed. Polymer-supported scandium-based Lewis acid (7) worked well in several carbon-carbon forming reactions in water (Schemes 12.67-12.69) [168]. It was suggested that the spacer could help to form hydrophobic reaction environments in water. As expected, (7) was easily recovered and reused. 

Scandium-based Lewis acid catalysts, especially its trifluoromethanesulfonate (Sc(OTf)3), are versatile catalysts that can accelerate a variety of organic reactions even in water as an environmentally benign solvent [48]. Various kinds of polymer-immobilization techniques have been developed as shown below. 

The microencapsulation technique has been developed by Kobayashi for the immobilization of metal Lewis acid catalyst in polymer [57]. The catalysts were immobilized on to polymers using physical environment by polymer backbones and interaction between 71 electrons of benzene rings of the polystyrenes and vacant orbitals of the catalysts. Microencapsulated scandium trifiuoromethanesul-fonate was easily prepared from polystyrene and Sc(OTf)3 in cyclohexane, which was successfully used in several important Lewis acid catalyzed carbon-carbon bond-forming reactions [57]. 

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]. 

In a related study the immobilization of scandium triflate considered a benzene-bridged sodium benzenesulfonate PMO support that was synthesized by surfactant-directed assembly between 2-(4-chlorosulphonylphenyl)ethyl trimethoxylsilane and l,4-bis-(triethoxysilyl) benzene (Scheme 8.11) [107],... 

In another procedure, the preparation of the polymer-supported scandium catalyst was performed according to Scheme 8.17 [70], Polystyrene, cross-linked with divinylbenzene, was treated with 5-phenylvaleryl chloride in carbon disulfide in the presence of aluminum trichloride. The carbonyl groups were then reduced using aluminum trichloride-lithium aluminum hydride in diethyl ether to afford double spacer resin. After sulfonation (chlorosulfonic acid/acetic acid), resin was treated with scandium(III) chloride in acetonitrile at room temperature to give the polymer-supported scandium chloride. Finally, it was treated with trifluo-romethanesulfonic acid to afford the immobilized triflate. 

Lanthanum and scandium inflates immobilized onto the mesoporous SBA and periodic meso-porous silica supports, respectively, are also effective for the same reaction under very close reaction conditions [105,107]. 

The importance of the Lewis acid cation in this process was shown from the lack of activity of pristine H-USY in the model aza-Diels-Alder of A-benzylidenaniline with cyclopentadiene leading to the tetrahydroquinoline product (Equation (8.48)) [136]. The immobilization of the scandium cation inside the pores of this zeolite with oidy a coordination position occupied by a triflate group changed completely the behavior of this zeolite affording an almost total yield in the condensation product. 

The Strecker-type reaction of benzaldehyde, aniline, and tributyltin cyanide was performed on polymer-immobilized scandium triflate [70]. The reaction proceeded cleanly in water (Equation (8.52)) to afford the corresponding a-amino nitrile derivative in high yield. 

Anwander and cowotkers (Gerstberger et al., 1999) immobilized rare-earth complexes on the mesopororrs silicate MCM-41 by first grafting [R N(SiHMe2)2 3(thf) c] onto MCM-41, followed by surface-confined ligand exchange with Hfod. This procedure yielded [MCM-41]R(fod) c(thf)3, (R = Sc, Y, La). The performance of this catalyst was tested in the hetero Diels-Alder reaction between trans-l-methoxy-3-trimethylsilyloxy-l,3-butadiene and ben-zaldehyde. A comparable activity was found for the yttiium(III) and scandium(III) com-... 

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