Asymmetric phase-transfer Michael

Catalytic Asymmetric Phase-Transfer Michael Addition to a,f -Unsaturated Esters 119... 

Scheme 6.3 Catalytic asymmetric phase-transfer Michael addition and counter anion effects.

Shibuguchi T, Mihara H, Kuramochi A, Ohshima T, Shibasaki M (2007) Catalytic Asymmetric Phase-Transfer Michael Reaction and Mannich-Type Reaction of Glycine SchiffBases with Tartrate-Derived Diammonium Salts. Chem Asian J 2 794... 

Shibuguchi T, Mihara H, Kuromachi A, Ohshima T, Shibasaki M. Catalytic asymmetric phase-transfer Michael reaction and Mannich-type reaction of glycine Schiff gases with tartrate-derived diammonium Salts. Chem. Asian J. 2007 2(6) 794-801. 

The use of chiral crown ethers as asymmetric phase-transfer catalysts is largely due to the studies of Bako and Toke [6], as discussed below. Interestingly, chiral crown ethers have not been widely used for the synthesis of amino acid derivatives, but have been shown to be effective catalysts for asymmetric Michael additions of nitro-alkane enolates, for Darzens condensations, and for asymmetric epoxidations of a,P-unsaturated carbonyl compounds. 

Whilst the use of Taddol as an asymmetric phase-transfer catalyst for asymmetric Michael reactions was only moderately successful, it was much more enantioselec-tive in catalyzing alkylation reactions. For this study, Belokon and Kagan employed alanine derivatives lib and 16a-c as substrates, and investigated their alkylation with benzyl bromide under solid-liquid phase-transfer conditions in the presence of 10 mol % of Taddol to form a-methyl phenylalanine, as shown in Scheme 8.8. The best results were obtained using the isopropyl ester of N-benzylidene alanine 16b as substrate and sodium hydroxide as the base. Under these conditions, (R)-a-methyl phenylalanine 17 could be obtained in 81% yield and with 82% ee [19]. Under the same reaction conditions, substrate 16b reacted with allyl bromide to give (R)-Dimethyl allylglycine in 89% yield and with 69% ee, and with (l-naphthyl)methyl chloride to give (R)-a-methyl (l-naphthyl)alanine in 86% yield and with 71% ee [20]. 

The use ofTaddol as an asymmetric phase-transfer catalyst has been adopted by other research groups. For example, Jaszay has used Taddol for Michael additions to a-aminophosphonate derivative 20, as shown Scheme 8.10 [22]. A range ofTaddol derivatives was investigated, but the best results were again obtained with the same catalyst employed by Belokon and Kagan. Thus, phosphoglutamic acid derivative 21 was obtained in 95% yield and with 72% ee when tert-butyl acrylate was employed as the Michael acceptor. 

The paramount importance of Michael additions as versatile C-C bond forming transformations was discussed in some detail earlier in this volume. Thus, it is not surprising that, besides the use of chiral PTCs in asymmetric a-alkylation reactions, their use for stereoselective Michael additions is one of the most carefully investigated reactions in asymmetric phase-transfer catalysis (328, 329). Accordingly, the additional use of this methodology in asymmetric total synthesis has been reported on several occasions. 

Michael-addition of diethyl(acetylamido) malonate to chalcone using asymmetric phase transfer catalyst (ephedrinium salts) in presence of KOH in the solid state has been carried outJ The yield is 56% with ee of 60% (Scheme 10). 

The catalytic enantioselective synthesis of ( )-paroxetine (69, Paxil GlaxoSmithKline, London, U.K.), which is a selective serotonin reuptake inhibitor being used for the treatment of depression, anxiety, and panic disorders, was executed as an application of the catalytic asymmetric mono -a-alkylation of 1,3-amide esters (Scheme 4.16). The characteristic feature of this protocol is the introduction of the C3-stereocenter first by the asymmetric phase-transfer alkylation before installing the C4-center by a diastereoselective Michael addition. Af,A -Di-p-methoxyphenyl malonamide... 

The introduction of a new catalyst system by Maruoka and coworkers using C2-symmetric binaphthyl-based chiral spiro ammonium salts 6 in 1999, paved the way for a new era in asymmetric phase-transfer catalysis. This PTC system was found to be highly effective for a variety of asymmetric transformations (e.g., Michael additions, a-amino acid syntheses, epoxidations. 

With respect to the application of tartaric acid-derived PTCs [22,23] for natural product synthesis, the work of Shibasaki s group should be highlighted herein. Using his powerful bidentate TaDiAS PTCs, asymmetric phase-transfer-catalyzed alkylations, Michael addition reactions, and Mannich-type reactions have been systematically carried out. 

Azoniaspirocycles have been derived from L-tartrate for use as phase-transfer catalysts <2002TL9535>. Catalyst 158 was synthesized in a straightforward manner (Equation 36), then used for catalytic asymmetric Michael reactions an example is shown (Equation 37). 

The first successful results of the asymmetric Michael addition under phase transfer catalyzed conditions were achieved by use of ingeniously designed chiral crown ethers 13 and 52.1441 The 3-keto ester 49 reacted with methyl vinyl ketone by use of 13 to give the Michael product 50 with excellent enantioselectivity but in moderate yield, as shown in Scheme 18. The Michael addition of methyl 2-phenylpropionate 51 to methyl acrylate afforded the diester 53 by use of another crown ether 52 in good yield with good enantioselectivity.1441 Various chiral crown ethers were studied to... 

Acrylonitrile, polymerization, 120 Activity of phase-transfer catalysts Sjj2 reactions, 170-175 weak-nucleophile Sj.Ar reactions, 175-182 Acyltetracarbonyl cobalt compound, cleavage in the carboxyalkylation of alkyl halides, 150 Addition reactions, Michael, catalytic asymmetric, 69,70f... 

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. 

A chiral quartemary ammonium salt works as a chiral-phase transfer catalyst, and this chemistry has been applied to asymmetric Michael reaction by Corey et al. (Scheme 8D.16) [33]. It has been shown that the cinchonidine salt 28, which has been designed by rigidifying... 

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