Michael reaction polymer-supported

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 strategy involving sequential 1,3-dipolar cycloadditions has been reported for the synthesis of novel bis-isoxazolo substituted piperidines 192a and 192b (Eqs. 18 and 19) [53]. It consists of the Michael addition of an unsaturated alkox-ide 185 to )3-nitrostyrene 184 followed by an INOC or ISOC reaction to provide isoxazolines 187-189 (Eq. 18 and Table 18). A polymer supported acyl chloride... 

Ley SV, Baxendale IR (2002b) New tools and concepts for modern organic synthesis. Nat Rev Drug Disc 1 573-586 Ley S V, Massi A (2000) J Comb Chem Polymer supported reagents in synthesis preparation of bicyclo[2.2.2]octane derivatives via tandem michael addition reactions and subsequent combinatorial decoration. 2 104—107 Ley SV, Schucht O, Thomas AW, Murray PJ (1999) Synthesis of the alkaloids ( )-oxomaritidine and ( )-epimaritidine using an orchestrated multi-step sequence of polymer supported reagents. J Chem Soc Perkin Trans 1 1251— 1252... 

The base-catalysed addition of thiols to Jt-electron-deficient alkenes is an important aspect of synthetic organic chemistry. Particular use of Triton-B, in place of inorganic bases, has been made in the reaction of both aryl and alkyl thiols with 1-acyloxy-l-cyanoethene, which behaves as a formyl anion equivalent in the reaction [1], Tetra-n-butylammonium and benzyltriethylammonium fluoride also catalyse the Michael-type addition of thiols to a,P-unsaturated carbonyl compounds [2], The reaction is usually conducted under homogeneous conditions in telrahydrofuran, 1,2-dimethoxyethane, acetone, or acetonitrile, to produce the thioethers in almost quantitative yields (Table 4.22). Use has also been made of polymer-supported qua-... 

Ishikawa and co-workers also reported a class of structurally modified guanidines for promotion of the asymmetric Michael reaction of ierf-butyl-diphenylimino-acetate to ethyl acrylate [124,125]. In addition to a polymer support design (Scheme 69), an optical resolution was developed to achieve chiral 1,2-substituted ethylene-l,2-di-amines, a new chiral framework for guanidine catalysis. The authors discovered that incorporating steric bulk and aryl substituents in the catalyst did improve stereoselec-tivitity, although the reactivity did suffer (Scheme 70, Table 4). 

Solid-phase synthesis is of importance in combinatorial chemistry. As already mentioned RuH2(PPh3)4 catalyst can be used as an alternative to the conventional Lewis acid or base catalyst. When one uses polymer-supported cyanoacetate 37, which can be readily obtained from the commercially available polystyrene Wang resin and cyanoacetic acid, the ruthenium-catalyzed Knoevenagel and Michael reactions can be performed successively [27]. The effectiveness of this reaction is demonstrated by the sequential four-component reaction on solid phase as shown in Scheme 11 [27]. The ruthenium-catalyzed condensation of 37 with propanal and subsequent addition of diethyl malonate and methyl vinyl ketone in TH F at 50 °C gave the adduct 40 diastereoselectively in 40 % yield (de= 90 10). 

Polymer-supported quaternary ammonium hydroxides have been used to catalyse Michael reactions between various alkyl methacrylates, acrylonitrile, and methyl vinyl ketone as acceptors and nitro or keto derivatives as donors.[116,117]... 

Another interesting feature of polymer-supported catalysts containing quaternary ammonium salts involves the development of enantioselective catalysis using salts derived from cinchonia or ephedra alkaloids.11341 The first application of such chiral supported catalysts in the Michael reaction between methyl 1-oxoindan-2-carboxylate and methyl vinyl ketone revealed a high chemical yield in condensation product (60-100 %) although the enantioselectivities were only moderate (ee <27 %). 

Hodge, P., Khoshdel, E. and Waterhouse, J. Michael reactions catalyzed by polymer-supported quaternary ammonium-salts derived from cinchona and ephedra alkaloids, J. Chem. Soc., Perkin Trans. 1, 1983, 2205-2209. 

Interestingly, the reaction of active methylene compounds having a nitrile group with a,/l-unsaturated carbonyl compounds give Michael adducts without contamination by the corresponding aldol products (Eq. 61) [89-92]. Murahashi and coworkers [89-91] proposed that the addition of the C-H bond to a low-valent ruthenium constitutes the initial step. Recently, Takaya and Murahashi [94] applied their aldol and Michael addition reactions to solid-phase synthesis using polymer-supported nitriles. 

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. 

Computational studies concerning theoretical approaches to the intrinsic basicity of neutral nitrogen bases have been reported, including those of phos-phoranimines. The non-ionic phosphazene bases BEMP (112), BTPP (113) and (114, R = Ph) appear to be excellent catalysts for the Michael addition reactions. Thus the yield of the coupling reaction of ethyl isocyanoacetate with l,2-bis(4-bromomethylphenyl)ethane is increased by the addition of the phosphazene base BEMP. Polymer-supported BEMP (P-BEMP) has been applied for the allylation of 2H-benzo[d]l,3-dioxolan-5-ol by allyl bromide. " Cyclodehydration of 1,2 diacylhydrazines by tosyl chloride in the presence of P-BEMP leads to excellent yields of 1,3,4,-oxadiazoles. Addition of P-BEMP also improves the yield of the Hofmann elimination step in the synthesis of tertiary mines using REM resin (polymer-bound acrylate ester). ... 

The heterobimetallic catalyst prepared from (R,R)-3-aza-benzyl-l,5-dihydroxy-l,5-diphenylpentane was used for the asymmetric Michael addition reaction of malo-nates and thiophenols to enones [49]. The polymer-supported version of the chiral... 

A similar approach has been examined by using polymer-supported ALB 91 (Scheme 3.25). When this polymeric chiral ALB catalyst was used for the asymmetric Michael reaction, the corresponding chiral adduct was obtained in 91% yield with 96% ee [48]. 

Ley, S.V. and Massi, A. (2(XX)) Polymer supported reagents in synthesis preparation of bicyclo[2.2.2]octane derivatives via tandem Michael addition reactions and subsequent combinatorial decoration. J. Comb. Chem. 2 104-107. 

The Michael addition reaction is one of the most important carbon-carbon bond forming reactions in organic synthesis, and several examples using polymer-supported reagents have been reported. For example, Bensa et al found that the Michael addition reaction of 1,3-dicarbonyl compounds with activated olefins as a Michael acceptor could be efficiently catalysed by PS-BEMP [35] (Scheme 6.6). The procedure does not require dry solvents or an inert atmosphere, and filtration of the catalyst gives substantially pure products. It is also... 

Surprisingly, there have been only few synthetic studies on polymer-supported asymmetric superbase reagents. Recently, Wannaporn and Ishikawa prepared a new chiral guanidine based polymer catalyst and applied it to the asymmetric Michael addition reaction of iminoacetate with methyl vinyl ketone [39] (Scheme 6.7). Although the catalyst shows only moderate levels of reactivity and enantioselectivity, the result demonstrates the possibility of expanding an exciting field of asymmetric synthesis using polymer-supported chiral superbase catalysts. 

Wannapom, D. and Ishikawa, T. (2005) Polymer-supported and polymeric chiral guanidines preparation and application to the asymmetric Michael reaction of iminoacetate with methyl vinyl ketone. Molecular Diversity, 9, 321-331. 

In addition, we have found that the stereochemistry of the Michael acceptor also plays an important role in the efficiency of phosphine-mediated intramolecular MBH reactions. In all examined cases with PPhs or polymer-supported phosphine as the catalyst, cyclization substrates enones 275 possessing (Z)-alkenes afforded the desired product 276 in a higher yield than ( )-275 under identical conditions (Scheme 1.99). The reason for this difference in reactivity is most likely steric in nature, as substrates where the p-substituent is ds to the electron-withdrawing substituent are more accessible to reaction with the nucleophilic catalyst than their trans counterparts. 

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