Site Michael reaction using

Table 7.6 Cyano-ethoxycarbonylation and Michael reaction using a site-isolated amine catalyst and related compounds [64].

Arai et al. also reported another BINOL-derived two-center phase-transfer catalyst 31 for an asymmetric Michael reaction (Scheme 6.11) [8b]. Based on the fact that BINOL and its derivatives are versatile chiral catalysts, and that bis-ammonium salts are expected to accelerate the reaction due to the two reaction sites - thus preventing an undesired reaction pathway - catalyst 31 was designed and synthesized from the di-MOM ether of (S)-BINOL in six steps. After optimization of the reaction conditions, the use of 1 mol% of catalyst 31a promoted the asymmetric Michael reaction of glycine Schiff base 8 to various Michael acceptors, with up to 75% ee. When catalyst 31b or 31c was used as a catalyst, a lower chemical yield and selectivity were obtained, indicating the importance of the interaction between tt-electrons of the aromatic rings in the catalyst and substrate. In addition, the amine moiety in catalyst 31 had an important role in enantioselectivity (34d and 34e lower yield and selectivity), while catalyst 31a gave the best results. 

While zeolites are mostly used in acid catalysts, there are various procedures to introduce basic sites with variable strength into these materials. Depending on the nature of the active site, one is able to selectively catalyze reactions with different basicity requirements, and this is probably the main virtue of base catalysis with zeolites. For instance, in a classical Knoevenagel condensation, the reaction selectivity can be decreased by a consecutive Michael reaction, since the Knoevenagel product can serve itself as a Michael receptor -. 

This sequence of reactions consists of an alkylation of a 1,3-diketone, followed by a Robinson annulation. The carbon-carbon double bond appears where the second carbonyl group of the diketone used to be and is the site of the ring-forming aldol reaction. A Michael reaction between the diketone and the Michael acceptor 3-buten-2-one adds the carbon atoms used to form the second ring, and an alkylation with CH3I adds the methyl group. 

The substrate 292 was specifically designed to prepare five-membered systems via a sequence of inter- and intramolecular Michael additions. This option is viable when active Michael acceptors such as methyl vinyl ketone are used, otherwise competing Michael reactions between two molecules of 292 are difficult to avoid. The reaction proceeds through intermediate 293, which contains both a Michael donor and acceptor site and undergoes spontaneous conversion into the cyclic product 294. 

The concepts surrounding the dendrimer synthesis have been lucidly presented [15, 22], The general synthetic strategy involves the repetitive alternation of a growth reaction and an activation reaction. Often these reactions have to be performed at many sites on the same molecule simultaneously. The growth reaction dictates the way by which the branching is introduced into a dendrimer. Many dendrimer syntheses rely upon traditional reactions, such as the Michael reaction or the Williamson ether synthesis while others involve the use of solid-phase synthesis or organotransition metal chemistry [1, 24]... 

As described in Sections 2.3.1.2 and 2.2.3, Choudary et al. recently revealed nanocrystalline magnesium oxide (NAP-MgO) as a recyclable heterogeneous catalyst [40, 45]. These authors extended the use of this new type of heterogeneous catalyst for the asymmetric Michael reaction of different acyclic enones with nitromethane and 2-nitropropane [69a]. In a Michael reaction of chalcone with nitromethane in THF solvent at -20°C, NAP-MgO/(lR,2R)-(-)-diaminocyclohexane (DAC) was found to be an excellent catalyst system (96% ee, 95% yield) (Scheme 2.32). This Michael reaction proceeds via the dual activation of both substrates (nucleophiles and electrophiles) by NAP-MgO. The Lewis basic site (O /O ) of the NAP-MgO activates the nitroalkanes, while the Lewis acid moiety (Mg /Mg )... 

The higher activity of primary amines in the reaction involving enones as Michael acceptors has also been extended to the use of different bifunctional catalysts (Scheme 3.19), which usually contain a primary amine functionality connected to a basic site by means of a chiral scaffold, as is the case in the use of 280 and 55. These diamine catalysts have been found to be excellent promoters of the Michael reaction of enones with cyclic 1,3-dicarbonyl compounds and malonates respectively, the tertiary amine basic site present at the catalyst structure being responsible for assisting in the deprotonation of the Michael donor in order to increase the concentration of the nucleophile species. In a different approach, bifunctional thiourea-primary amine catalyst 56a has also... 

When sodium cations in the mont interlayer are exchanged with Sc + using an aqueous solution of Sc(OTf)j, a monomeric aqua complex, [Sc(H20)g] +, was formed in the interlayer space [104]. The Sc " -mont could efHdently catalyze the Michael reaction of 1,3-dicarbonyl compounds with enones in water solvent. The Michael addition reaction of 1,3-dicarbonyl compounds with enones provides access to 1,5-dioxo synthons, which can be transformed easily into cyclohexanone derivatives for use as important intermediates in steroid and terpenoid syntheses. Initially, both the 1,3-dicarbonyl compound and the enone coordinate with the Sc + center, which acts as a Lewis add site. Subsequently, successive carbon-carbon bond formation produces an intermediate Sc-alcoholate, followed by protolysis to afford the Michael adduct and regenerate the initial Sc species, [Sc(H20)g] +. The importance of coordination of both the substrates is evidenced by IR spectrometry. 

In contrast to the extensive use of nitroolefins in asymmetric Michael additions [10], the vinylogous analogues, nitrodienes and nitroenynes, are less frequently utilized in the conjugate addition of enolate equivalents, despite the significant synthetic utility of the resulting products which possess carbonyl, nitro, and olefin functionalities. Likewise, studies on the hetero-Michael reaction with these acceptors have been very limited, possibly because of apprehension of the site-selectivity issue [11]. 

Regioselective reductions of a,P-imsaturated ketones were performed in water containing carbohydrate-derived amphiphiles. Cyclohexenones were converted to allylic alcohols, whereas cyclopentenones gave substantial amounts of 1,4-reduction (Denis et al, 1996). Such a use of concentrated aqueous solutions of carbohydrates as the reaction medium has been described by Lubineau (1993, 1994b) in the context of many different chemical transformations including Diels-Alder, aldol and Michael reactions, as well as reductions of a,p-unsaturated ketones, all dealing with the chemistry of the carbonyl group either as the reaction site or as the activation site (Scheme 4.17). 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

The yields obtained after 10 min in a batch reactor with MgO, CaO, or SrO exceeded 92%, whereas with BaO the yield was lower (72%), probably because of its low surface area (2m /g). When alkaline earth hydroxides were used as basic catalysts, the yields were lower than for the corresponding oxides. The most active hydroxides were Sr(OH)2 8H2O and Ba(OH)2 8H2O, which gave the additional compound in yields of 75% and 70%, respectively, whereas carbonates were characterized by very poor activity. As observed for other reactions, the catalytic activity of MgO strongly depends on the pre-treatment temperature. A maximum in activity was observed when MgO was pre-treated at 673 K. At this temperature, decomposition of Mg(OH)2 to MgO is not complete, and Mg(OH)2 remains in the catalyst. It was suggested that the surface OH groups act as active sites, as for the Michael addition reactions described above. 

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