Michael silica support

Silica-supported Lewis acids are useful catalysts with microwave irradiation for conjugate additions. The silica-supported catalysts are obtained by treatment of silica with ZnCh [Si(Zn)], Et2AlCl [Si(Al)] or TiCl4 [Si(Ti)] [ 150-152], The Michael addition of methyl a-acetamidoacrylate (196) with indole (2) under Si(M) heterogeneous catalysis assisted by microwave irradiation afforded the alanine derivative 197 within 15 min and/or bis-indolyl 198, depending on the reaction conditions (Scheme 45) [153]. While the bis-indolyl product 198 is only formed when Si(Zn) was used as catalyst, the alanine derivative 197, as a single product is formed under thermal heating in a yield of 12%. The best yields were observed with Si(Al) (Table 5). The product 198 was obtained by elimination of acetamide followed by a-Michael addition between intermediate 199 with a second mole of indole. 

The Michael addition of methyl a-acetamidoacrylate (196) with pyrrole (1) under silica-supported Lewis acid (Si(M) Si(Zn), Si(Al) and Si(Ti)) assisted by microwave irradiation (MW) afforded the alanine derivatives 395 and 396 dependent on the reaction conditions (Scheme 81) [153]. Both MW and thermal activation for pyrrole gave only Michael product 396, whereas alanine derivatives 395, which are the a-Michael addition product, and 396 were observed with A1 and Ti-catalyst. This behavior shows that aluminium and titanium Lewis acids can form a new acceptor in an irreversible way. The Si(M) or p-TsOH catalyzed reactions of N-benzylpyrrolc 397 with the acrylate 196 under MW gave the product 398 as sole product. The reaction yield has been increased by using a catalytic amount of p-TsOH (Scheme 82). 

Since silica is such a common support for immobilization, the effect of the weakly acidic silanol groups has been studied. A cooperative silanol effect is thought to improve the catalytic activity of mesoporous silica-supported amines in base-catalyzed reactions such as the nitroaldol (Henry) condensation [6, 7], Knoevenagel condensation [6, 8,9], and Michael addition [6]. Thus immobilizing amines onto supports with stronger acid groups could be expected to further increase the catalytic activity. 

Oxidations. Glycol and microwave irradiatiim same method seems to I titanium/tartaric acid caul hydrogen peroxide as the 1 A percarboxylic acid, orthosilicate to aqueous eti is hydrolyzed and treated 1 Miscellaneous reactit Friedel-Crafls reaction derivatization that introd catalyzing Michael react supported on silica gel by... 

A silica-supported phenoxide gave a 99% yield in the Michael reaction (6.25).87... 

The available information about supported metals as catalysts for Michael reactions will be commented upon, with emphasis on selected silica supports [93]. 

Silica-supported Lewis acids (Si(M)l in conjunction with microwave irradiation were employed for the Michael addition of pyrrole (63) with a-acctamidoacrylate (64) as a route to pyrrolyl alanine derivatives 65 <01T5421>. 

Another group active in this field of research is led by Michael Buchmeiser, who has reported NHC-supported, catalyst systems anchored to both monolithic polymer and silica supports. The first example from this group involved the preparation of the norbornene-functionalized NHC salt 13, and the subsequent tethering of this molecule to a Runorbornene-derived monolithic material (14 Scheme 5.1) using ROMP [25]. The free carbene was then generated on the support and treated... 

Scheme 13.5 Michael reaction catalyzed by Yb(OTf)3 on silica support.

Microwave-assisted preparation of a- and P-substituted alanine derivatives by a-amido alkylation or Michael addition reaction in presence of silica supported Lewis acids as catalyst has been reported by de la Hoz et al. (2001). 

The Michael reaction involving addition to carbon-carbon double bonds containing an electron-withdrawing group is catalysed by base. A variety of heterogeneous bases which can be reused are known, including alumina, KF on alumina and phenolates supported on silica, the last having proved particularly effective for addition of /3-keto esters to enones (Scheme 1.7). 

Bis(indolyl)nitroethanes are obtained readily in 7-10 min in high yields (70-86%) on fine TLC-grade silica gel (5-40 pm) by Michael reaction of 3-(2 -nitrovinyl) indole with indoles. The same reaction reported requires 8-14 h for completion at room temperature [77]. Several functionalized resins have been prepared from Merrifield resin via a MW-assisted procedure that utilized mixed solvent system to facilitate the swelling of resins and coupling with microwaves [78], These resins can function as solid supports or polymeric scavengers in solid phase synthesis. 

Miscellaneous reactions. Mediated by grounded FeClj and silica gel the Friedel-Crafts reaction of arenes with ArCCl, provides benzophenones. After derivatization that introduces dimethylaminopropyl pendants the silica is useful for catalyzing Michael reactions. Alcohols are attached to carboxylic acids which are supported on silica gel by esterification. ... 

Michael reactions. Many commonly known conjugate additions can be carried out in water" in the presence of Yb(OTf)j, sometimes also at high pressure and sometimes on silica gel supports. ... 

Another novel approach to labelling molecules with carbon-11 has been published by Somawardhana, Sajjad and Lambrecht . These workers have absorbed one of the reactants required for the synthesis on a solid support and the reaction has been done by adding the other reagents to the solid support and heating the mixture in a sealed vial. One example illustrating their methodology is the formation of [l- C]putrescine. The H CN is trapped on a potassium-hydroxide-coated silica gel. Then, acrylonitrile is added, and the reaction tube sealed at both ends. After the tube had been heated at 75 °C for 5 minutes, the Michael addition product was eluted from the solid support and the solvent evaporated. Finally, the nitrile groups were reduced with a borane-dimethylsulphide complex in THF (equation 77). The total reaction time was less than 40 minutes and the product was obtained in a 53% radiochemical yield. 

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