Michael reaction enantioselective

The enantioselective Michael reaction of malonates to nitroolefins catalysed by bifunctional amino-thioureas has recently been reported by Take-moto [161]. Excellent ee (75-93%) were obtained with diethylmalonate after solvent optimisation, toluene being the best solvent both for the activity and for the selectivity. Substituted malonates were then reacted with various nitroolefins under the same conditions. Excellent enantioselectivities were observed (Scheme 45). 

Bifunctional thiourea-catalysed enantioselective Michael reaction has been achieved. The thiourea moiety and an amino group of the catalyst activated a nitroolefin and a 1,3-dicarbonyl compound, respectively afford the Michael adduct with high enantioselectivity.177,178 Thioureas work as one of the most effective and general enantioselective nitro-Mannich reaction and carbonyl cyanation catalyst.179,180... 

Enantioselective Michael reactions have been achieved using both the Rh-based CATHy catalysts [89 a] and the Ru-based Noyori catalysts [89 b]. 

Sodeoka and coworkers reported a chiral Pd-catalyzed enantioselective Michael reaction of 1,3-diketones and (3-ketoesters to enones, [Eq. (13.18)]. It was proposed that the catalyst 29 exists in equilibrium with 30 through liberating H2O... 

A chiral phase transfer catalyst was dissolved in ionic liquid media for the enantioselective Michael reaction of dimethyl malonate with l,3-diphenylprop-2-en-l-one with K2CO3 203). The phase-transfer catalyst was a chiral quininium bromide (Scheme 20). The reaction proceeded rapidly with good yield and good enantioselectivity at room temperature in all three ionic liquids investigated, [BMIM]PF6, [BMIM]BF4 and [BPy]BF4. In the asymmetric Michael addition, the enantioselectivity or the reaction in [BPy]Bp4 was the same as in conventional organic solvents. 

With respect to the site at which the new asymmetric carbon center is created, the catalytic enantioselective Michael reaction can be categorized into two groups (Fig. 1) in Type I an asymmetric center is generated on the Michael donor side in Type II an asymmetric center is generated on the Michael acceptor side. 

Figure 2. Types of catalyst for enantioselective Michael reactions.

Activation of enones by formation of an iminium cation is an interesting strategy that has been highlighted for organocatalysis in recent publications. A similar concept has been investigated for the enantioselective Michael reaction of malo-... 

Corma, A., Iborra, S., Rodriguez, I., Iglesias, M. and Sanchez, F.MCM-41 heterogenized chiral amines as base catalysts for enantioselective Michael reaction, Catal. Lett., 2002, 82, 231-242. 

Asymmetric 1,4-addition of RCu-BF,. Chiral a,(3-unsaturated esters (2) derived from (IR)-l undergo a highly enantioselective Michael reaction with CH,Cu-BF particularly when stabilized with tri-n-butylphosphinc or cyano group (equation I). 

In recent years, many chiral catalysts for the enantioselective synthesis of optical active 1,5-dicarbonyl compounds have been developed, such as chiral crown ethers with potassium salt bases and chiral palladium complexes, including bimetallic systems. Nakajima and coworkers reported on enantioselective Michael reactions of S-keto esters to a,/3-unsaturated carbonyl compounds in the presence of a chiral biquinoline N,N dioxide-scandium complex, which catalyzed the additions in high yields and with enan-tioselectivities up to 84% ee . Kobayashi and coworkers found that the combination of Sc(OTf)3 with the chiral bipyridine ligand 149 (equation 41) was also effective as a chiral catalyst for asymmetric Michael additions of 1,3-dicarbonyl compounds 147 to a,/3-unsaturated ketones 148. The corresponding Michael adducts 150 were obtained in good to high yields with excellent enantiomeric excesses in most cases (Table 10). 

Krause, N. Hoffmann-Roder, A. Recent Advances in Catalytic Enantioselective Michael Reactions, Synthesis 2001,171-196. 

Enantioselective Michael Additions. Amine 1 has also been used as an effective ligand for enantioselective Michael reactions of ketone lithium enolate donors with various benzylidene acceptors. As representative examples, the lithium enolates of aryl methyl ketones were reacted with dimethyl benzylidene-malonate in the presence of 1 (eq 9). The lithium enolate was generated from the corresponding ketone by treatment with hex-amethyldisilazide in the presence of lithium bromide in toluene. The resulting enolate was then exposed to 1 and allowed to stir for 30 min to form the desired ternary complex. After addition of the benzylidene acceptor, the desired products were isolated in acceptable yields and with high % ee. 

Christoffers J, Baro A. Construction of quaternary stereocenters new perspectives through enantioselective Michael reactions. Angew. Chem., Int. Ed. 2003 42 1688-1690. 

Okino T, Hoashi Y, Takemoto Y (2003) Enantioselective michael reaction of malonates to nitroolefins catalyzed by bifunctional organocatalysts. J Am Chem Soc 125 12672... 

Sevin, A., Masure, D., Giessner-Prettre, C., Pfau, M. A theoretical investigation of enantioselectivity Michael reaction of secondary enamines with enones. Helv. Chim. Acta 1990, 73, 552-573. 

The simple chiral lithium alkoxide 5 was applied to the Michael reaction of methyl phenylacetate with methyl acrylate to give the corresponding adduct in 84% ee (Eq, (12.6)) [19]. The catalytic enantioselective Michael reaction was also effected by the chiral alkoxide 5. 

A variety of nucleophiles can be added in a conjugate manner to a,p-unsaturated ketones. The reaction is reversible, so the main difficulty is finding conditions that drive the equilibrium to the right. For catalytic enantioselective Michael reactions, see Krause, N. Hoffinann-Roder, A. Synthesis 2001,171-196. For intramolecular Michael reactions see Little, R.D. Masjedizadeh, M. R. Wallquist, O. Mcloughlin, J. 1. Org. React. 1995, 47, 315-552. 

This catalyst has also been successfully employed for enantioselective Michael reaction" (Scheme 5.6). 

CATALYTIC ENANTIOSELECTIVE MICHAEL REACTION CATALYSED BY WELL-DEFINED CHIRAL RUTHENIUM-AMIDO COMPLEXES... 

Michael reactions. A BINOL complex prepared from (i-PrO)jLa promotes enantioselective Michael reactions with excellent results. 

There are also examples of enantioselective Michael reactions on helerogcni/ed chiral amines (cinchonidine and cinchonine) (Figure 20d) [I65. Further examples ol Michael additions use nitromcthane, maloniirile. diethyl malonaie. cyanoaceianiide or thiols as donors and methyl vinyl ketone, methyl aciylaic and simple and substituted chalconcs as acceptors 70. 81. 114. 245. 265, 266). As for the catalysts, they can be cation-promoted Ba(OM) [70], hydroxyapatite 1245]. supported KF (114). alkaline carbiuiaies (I02. hydrolalciies (2(>51... 

Ye, W., Jiang, Z., Zhao, Y. et a/. (2007) Chiral bicyclic guanidine as a versatile Brdnsted base catalyst for the enantioselective Michael reactions of dithiomalonates and P-keto thioesters. Advanced Synthesis and Catalysis, 349, 2454-2458. 

D. Coquiere, B. L. Feringa, G. Roelfes, DNA-based catalytic enantioselective Michael reactions in water, Angew. Chem. Int. Ed., 2008, 46, 9308-9311. 

Enantioselective Michael reaction of propanal to frans-p-nitrostyrene. 

Table 2.26 Enantioselective Michael Reaction of Propanal to Trans-p-N itrostyrene ...

Table 2.27 Enantioselective Michael Reaction of Nitroalkenes and Aldehydes ...

Scheme 1.2 The enantioselective addition of MeOH to methyl phenyl ketene reported by Pracejus and the quinine-catalyzed enantioselective Michael reaction reported by Wynberg.

Scheme 2.5 Enantioselective Michael reactions of ketones with nitroalkenes catalyzed by proline and proline-tetrazole analogues.

Scheme 2.7 Enantioselective Michael reactions of a-hydroxy- and a-aminoketones with nitroalkenes catalyzed by 15a.

Scheme 2.22 Enantioselective Michael reaction between cyclic ketones and 1,4-diaryl...

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