Lewis Michael reactions

Conditions for effecting conjugate addition of neutral enolate equivalents such as silyl enol ethers in the presence of Lewis acids have been developed and are called Mukaiyama-Michael reactions. Trimethylsilyl enol ethers can be caused to react with electrophilic alkenes by use of TiCl4. These reactions proceed rapidly even at -78° C.308... 

Jenner investigated the kinetic pressure effect on some specific Michael and Henry reactions and found that the observed activation volumes of the Michael reaction between nitromethane and methyl vinyl ketone are largely dependent on the magnitude of the electrostriction effect, which is highest in the lanthanide-catalyzed reaction and lowest in the base-catalyzed version. In the latter case, the reverse reaction is insensitive to pressure.52 Recently, Kobayashi and co-workers reported a highly efficient Lewis-acid-catalyzed asymmetric Michael addition in water.53 A variety of unsaturated carbonyl derivatives gave selective Michael additions with a-nitrocycloalkanones in water, at room temperature without any added catalyst or in a very dilute aqueous solution of potassium carbonate (Eq. 10.24).54... 

Heterobimetallic asymmetric complexes contain both Bronsted basic and Lewis acidic functionalities. These complexes have been developed by Shibasaki and coworkers and have proved to be highly efficient catalysts for many types of asymmetric reactions, including catalytic asymmetric nitro-aldol reaction (see Section 3.3) and Michael reaction. They have reported that the multifunctional catalyst (f )-LPB [LaK3tris(f )-binaphthoxide] controls the Michael addition of nitromethane to chalcones with >95% ee (Eq. 4.140).205... 

Mukaiyama reaction (Lewis acid-catalyzed Michael reaction) with electron-poor olefins, ketals and acetals, and enones 32... 

Michael reactions of silyl enol ethers.1 2 3 The silyl enol ether of 1-acetylcy-clohexene (1) undergoes two consecutive Michael reactions with an a,p-enone or -enal in the presence of this Lewis acid to form 1-decalones. 

It is significant to note that this reaction is highly unusual since the prochiral element resides entirely on the nucleophile. The chiral Lewis acid exerts control of en-antiofacial selectivity by proctor through tight control of the presumed heterocycloaddition transition state, Scheme 27. In effect, extremely high fidelity is necessary to orient the 2n component with respect to the 4ji component coordinated to the chiral Lewis acid. The factors that control the diastereoselectivity in the Mukaiyama Michael reaction of crotonylimides could also control enantioselectivity in the amination reaction. That selectivities on the order of 99% ee are observed in this reaction is testament to the level of control exerted by these catalysts. 

There are only few examples of organic reactions catalysed effectively by Lewis acids which can be carried out in pure water without any organic co-solvent. While water can be used successfully for the uncatalysed Michael addition of 1,3-diketones (Table 4, entry D)22, the corresponding reaction of /i-kctocsters does not give satisfactory results. On the other hand, the Yb(OTf)3 catalysed Michael reaction of various /i-ketoesters (Table 21, entry A)257 and a-nitroesters (Table 21, entry B)258 takes place. 

By 1989 Mukaiyama had already explored the behaviour of phosphonium salts as Lewis acid catalysts. It was possible to show that the aldol-type reaction of aldehydes or acetals with several nucleophiles and the Michael reaction of a,j3-unsatu-rated ketones or acetals with silyl nucleophiles gave the products in good yields with a phosphonium salt catalyst [116]. In addition, the same group applied bisphosphonium salts as shown in Scheme 45 in the synthesis of ]3-aminoesters [117]. High yields up to 98% were obtained in the reaction of A-benzylideneaniline and the ketene silyl acetal of methyl isobutyrate. Various analogues of the reaction parteers gave similar results. The bisphosphonium salt was found to be superior to Lewis acids like TiCl and SnCl, which are deactivated by the resulting amines. 

Hydroamination of Alkenes Kobayashi et at. found that several transition metal salts displayed high catalytic activity in aza-Michael reactions of enones with carbamates, while conventional Lewis acids (BF3-OEt2, A1C13, TiCl4...) were much less active. 

The application of diazo coupling is somewhat limited by the availability of the p-aminophenyl glycosides, particularly of those of the oligosaccharides. Their precursors, the p-nitrophenyl glycosides, are usually obtained by the condensation of a per-O-acetylated glycosyl halide with p-nitrophenol in ethanol (Michael reaction)19,20 or by the reaction of a per-O-acetylated sugar with p-nitrophenol in the presence of a Lewis acid catalyst (Helferich reaction).21 p-Nitrobenzyl 1-thioglycosides have also been prepared by the condensation of the... 

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). 

Table 3. Lewis Acid Promoted Michael Reaction of q2-Pyrrole...

With the exception of Yb(OTf)3 3H2O, indium salts and Bronsted acids, there are several metal-based Lewis acid catalysts available for these Michael reactions, such as a CeCl3 7H20-NaI combination supported on... 

Molecular iodine-promoted Michael addition is a simple and efficient method for generating 2-pyrrolyl-2-phenyl-l-nitroalkanes in good yields (Scheme 67) [86]. Cr+3-Catsan (Cr+3 exchanged commercially available montmorillonite clay) and ZnCl2, which were first used as Lewis acids for Michael reactions of pyrrole, showed different selectivity under the same conditions [221], In general, while the reactions catalyzed by Cr+3-Catsan... 

The second part of the chapter deals with several kinds of asymmetric reactions catalyzed by unique heterobimetallic complexes. These reagents are lanthanoid-alkali metal hybrids which form BINOL derivative complexes (LnMB, where Ln = lanthanoid, M = alkali metal, and B = BINOL derivative). These complexes efficiently promote asymmetric aldol-type reactions as well as asymmetric hydrophosphonylations of aldehydes (catalyzed by LnLB, where L = lithium), asymmetric Michael reactions (catalyzed by LnSB, where S = sodium), and asymmetric hydrophosphonylations of imines (catalyzed by LnPB, where P = potassium) to give the corresponding desired products in up to 98% ee. Spectroscopic analysis and computer simulations of these asymmetric reactions have revealed the synergistic cooperation of the two different metals in the complexes. These complexes are believed to function as both Brpnsted bases and as Lewis acids may prove to be applicable to a variety of new asymmetric catalytic reactions.1,2... 

Michael reactions. This system promotes a Michael addition of silyl enol ethers to a,(3-unsaturated thiolesters, which are excellent Michael acceptors. Trityl salts are less effective, as are Lewis acids in combination with SnCl2. 

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