Catalysis Michael reaction

A-methoxy-carbonyl-2-pyrroline 235 Michael reactions, nickel catalysis 97-8 monophospholanes with pendant f-BuS group 17,19... 

Verkade and co-workers have shown the usefulness of their phosphazanes in various stoichiometric as well as catalytic reactions <1999PS(144)101>. Compound 290 was used to promote the cyanohydration of benzaldehyde with trimethylsilyl cyanide (TMSCN). The cyanohydrin was isolated in 95% yield, but no enantioselectivity was noticed <2002JOM(646)161>. Compounds 291 and 292 were attached to dendrimers and shown to be effective in the catalysis of Michael reactions, nitroaldol reactions, and aryl isocyanate trimerizations <2004ASC1093>. 

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. 

Takemoto and co-workers designed a small hbrary of thiourea cyclohexane-diamine derived catalysts for the Michael reaction of malonates to nitrolefins [15]. The authors observed an interesting trend in catalysis the reaction only proceeded enantioselectively and in decent yields when the catalyst possessed both thiourea... 

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). 

Monoalkylation of a-isocyano esters by using tert-butyl isocyano acetate (R = fBu) has been reported by Schollkopf [28, 33]. Besides successful examples using primary halides, 2-iodopropane has been reported to produce the a-alkylated product (1) as well by this method (KOfBu in THF). In the years 1987-1991, Ito reported several methods for the monoalkylation of isocyano esters, including the Michael reaction under TBAF catalysis as described earlier [31], Claisen rearrangements [34], and asymmetric Pd-catalyzed allylation [35]. Finally, Zhu recently reported the first example of the introduction of an aromatic substituent by means of a nucleophilic aromatic substitution (Cs0H-H20, MeCN, 0°C) in the synthesis of methyl ot-isocyano p-nitrophenylacetate [36]. 

A bifunctional mechanism involving enamine catalysis [55, 58, 77] was clearly indicated in the Michael reactions promoted by catalyst 101. The observed... 

The utility of C9-epi-DHQ thiourea 122 for the catalysis of asymmetric Michael reactions [149-152] was further demonstrated by the Wang group [282] in 2006. 

Scheme 6.139) [293]. Ricci and co-workers explained the outcome of their aza-Michael reaction with the mechanistic picture visualized in Scheme 6.140 C9-epi-QN -derived thiourea 121 displayed a bifunctional mode of catalysis, which simultaneously activated both the chalcone Michael acceptor and the donor O-benzylhydroxylamine through explicit hydrogen bonding. 

Another significant development in oxazoline chemistry is the application of oxazoline-containing ligands for asymmetric catalysis, such as palladium-catalyzed allylic substimtions, Heck reactions, hydrogenations, dialkylzinc additions to aldehydes, and Michael reactions. The discovery of diastereoselective metalation of chiral ferrocenyloxazolines has further expanded the availability of chiral ligands for metal-catalytic reactions. 

Catalysis of Michael reactions.5 Michael reactions proceed at 25° in THF when catalyzed by potassium f-butoxide absorbed on xonotlite, Ca6Si6017(0H)2,6 or by KF adsorbed on alumina. 

The iron catalysis of vinylogous Michael reactions is not only restricted to dimerizations. The y-donor 46b can be converted with MVK (41a) to give the 1,7-dioxo-constituted product 49 when the catalyst is Fe(III) (Scheme 8.21) [75]. If NaOMe in MeOH is applied as the catalyst, reaction of the dienolate of donor 46b in the a-position with acceptor 41a proceeds via a normal Michael reaction and 1,5-dioxo-constituted product 50 is obtained. 

Asymmetric catalysis with chiral ligands [82] is commonly considered to be advantageous instead of using chiral auxiliaries. Catalytic asymmetric Michael reactions are known [83], but not with iron as the catalytically active metal. Only two reports on iron catalyzed catalytic asymmetric Michael reaction with dipeptides [84] or diamino thioethers [85] exist, but the enantioselectivities were disappointing (18% ee and 10% ee, respectively). 

Michael Reactions in Ionic Liquids and Heterogeneous Catalysis... 

A biphenyl and ct-methylnaphthylamine-derived chiral quaternary ammonium salt 23d, which was shown by Lygo to be effective for the asymmetric alkylation of Schiffs base 20, was also effective in the Michael reaction (Scheme 7.12) [43]. Notably, the enantioselectivity was highly dependent on the reaction conditions and substrates used. The Michael reaction of imine esters such as benzhydryl and benzyl esters with a,p-unsaturated ketones under solid-liquid phase-transfer catalysis conditions afforded the Michael adduct in up to 94% ee and 91% ee, respectively, while the tert-butyl ester showed moderate enantioselectivity (Scheme 7.12). Interestingly, in contrast to earlier reports, acrylate [42] and acrylamides failed to undergo the Michael reaction under these optimized conditions. 

Stereoselective formation of carbon carbon and carbon heteroatom bonds remains an important goal in synthetic chemistry. Very recently lanthanide alkoxides were successfully utilized in enantioselective C-C bond forming reactions. Catalysis of aldol, cyanosilylation, nitroaldol and Michael reactions has been ascribed to the basic character of lanthanide alkoxides [158, 250, 251]. Ln3(OfBu)9 was successfully employed in test runs and subsequently optically active bidentate ligands were used (Fig. 35) [250a]. 

Scheme 1. Catalysis ofthe reaction of indanone 2-carboxylate with methyl vinyl ketone to afford Michael adduct 2...

By simulating evolution in vitro it has become possible to isolate artificial ribozymes from synthetic combinatorial RNA libraries [1, 2]. This approach has great potential for many reasons. First, this strategy enables generation of catalysts that accelerate a variety of chemical reactions, e.g. amide bond formation, N-glycosidic bond formation, or Michael reactions. This combinatorial approach is a powerful tool for catalysis research, because neither prior knowledge of structural prerequisites or reaction mechanisms nor laborious trial-and-error syntheses are necessary (also for non-enzymatic reactions, as discussed in Chapter 5.4). The iterative procedure of in-vitro selection enables handling of up to 1016 different compounds... 

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 %). 

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