Asymmetric Aldol and Michael Reactions

1 Direct catalytic asymmetric aldol reaction ofaoc-hydroxyketone promoted by an 

Masakatsu Smbasaki, Shigeki Matsunaga and Naoya Kumagai. 202 

2 Synthesis of (2R,3S)-3-cyclohexyl-2,3-dihydroxy-1 -(2-methoxyphenyl)-1-propanone by the second generation Et2Zn/linked-BINOL = 4/1 complex 

2 Highly enanttoselecitve direct aldol reaction catalysed by a novel small organic MOLECULE 

Zhuo Tang, Liu-Zhu Gong, Ai-Qiao Mi and Yao-Zhong Jiang. 208 

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Between 2011 and 2012 Schitzer et al. introduced the sulfate anion of the ionic compounds 31 (Figure 11.5) as a catalyst for the asymmetric aldol" " and Michael reactions in the ionic liquid [bmim][NTf2] (buthyl-methyl-imidazolium bis-trifluorosulfonylimide), with good yields but only moderate... 

Figure 11.5 Ionic organocatalysts 31 for the asymmetric aldol and Michael reactions in ionic liquids.

The basic character of lanthanide alkoxides such as Lu3(Of-Bu)9 seem to effect aldol, cyanosilylation, aldol, and Michael reactions [111]. Complexes 2 and 22, abbreviated as LnMB (Ln = lanthanide, M = alkali metal, B = BR IOL) [112] were thoroughly studied in the catalytic, asymmetric nitroaldol reaction (Henry reaction eq. (10)) [113]. 

As a different family of heteroaromatic-substituted organocatalysts, imidazole-and triazole-based compounds have been known to be quite effective for asymmetric aldol and Michael addition reactions. Figure 1.6 Usts representative examples of these catalysts. 

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... 

Notz W, Tanaka F, Barbas CF (2004) Enamine-based organocatalysis with proline and diamines the development of direct catalytic asymmetric aldol, Mannich, Michael, and Diels-Alder reactions. Acc Chem Res 37(8) 580-591... 

Aldol reactions using a quaternary chinchona alkaloid-based ammonium salt as orga-nocatalyst Several quaternary ammonium salts derived from cinchona alkaloids have proven to be excellent organocatalysts for asymmetric nucleophilic substitutions, Michael reactions and other syntheses. As described in more detail in, e.g., Chapters 3 and 4, those salts act as chiral phase-transfer catalysts. It is, therefore, not surprising that catalysts of type 31 have been also applied in the asymmetric aldol reaction [65, 66], The aldol reactions were performed with the aromatic enolate 30a and benzaldehyde in the presence of ammonium fluoride salts derived from cinchonidine and cinchonine, respectively, as a phase-transfer catalyst (10 mol%). For example, in the presence of the cinchonine-derived catalyst 31 the desired product (S)-32a was formed in 65% yield (Scheme 6.16). The enantioselectivity, however, was low (39% ee) [65],... 

In this chapter, we present the contributions of computational chemistry toward understanding the mechanism and chemistry for three reactions involving nucleophilic attack. The 8 2 reaction, with emphasis on the gas versus solution phase, is presented first Next we describe the critical contribution that computational chemists made in developing the theory of asymmetric induction at carbonyl and vinyl compounds. The chapter concludes with a discussion on the collaborative efforts of synthetic and computational chemists in developing organic catalysts, especially proline and proline-related molecules, for the aldol, Mannich and Michael reaction, and other related reactions. 

Notz, W., Tanaka, F., Barbas, C. F., III. Enamine-Based Organocatalysis with Proline and Diamines The Development of Direct Catalytic Asymmetric Aldol, Mannich, Michael, and Diels-Alder Reactions. Acc. Chem. Res. 2004, 37, 580-591. 

General comments about the Michael reaction procedures are analogous to those developed in the aldol and Mannich reactions.For example, the O-TMS-protected diphenylprolinol compound 20 in cooperation with benzoic acid catalyses the asymmetric Michael addition of aldehydes to nitroalkenes, in a simple, practical and efficient procedure. Benzoic acid promotes the rapid formation of the enamine intermediate and the reaction takes place in the highly concentrated organic phase of the aqueous biphasic system. 

The book comprises 8 chapters. The first provides background, introduces the topic of asymmetric synthesis, outlines principles of transition state theory as applied to stereoselective reactions, and includes the glossary. The second chapter details methods for analysis of mixtures of stereoisomers, including an important section on sample preparation. Then follow four chapters on carbon-carbon bond forming reactions, organized by reaction type and presented in order of increasing mechanistic complexity Chapter 3 is about enolate alkylations. Chapter 4 nucleophilic additions to carbonyls. Chapter 5 is on aldol and Michael additions (2 new stereocenters), while Chapter 6 covers rearrangements and cycloadditions. The last two chapters cover reductions and oxidations. 

Asymmetric aldol reaction of silyl enol ethers. (16,221-222). The use of TiCI4 as promoter of aldol condensation of silyl enol ethers with aldehydes, first reported in 1973 (6,590-591), has seen wide use, but has the drawbacks that 1 cquiv. of the Lewis acid is required and that an asymmetric version requires use of chiral aldehydes or chiral silyl enol ethers. More recently, the combination of a salt and a weak Lewis acid, neither effective catalysts themselves, was found to be effective in catalytic (5-10 mol %) amounts. Further research showed that tin(ll) triflatc when coordinated with a chiral diamine can effect catalytic asymmetric allylation of aldehydes (13,302) and Michael reactions (15,313-314), even though this complex cannot promote aldol condensation. Eventually the combination of tin(Il) triflatc, a chiral diamine,... 

Transition metal enolate complexes have been prepared with most or all transition metals, and the enolate ligands have been shown to adopt a variety of bonding modes. Bofli early and late transition metal enolate complexes are intermediates in a number of important catalytic processes. Early transition metal enolates are important intermediates in asymmetric aldol reactions that exploit the Lewis acidic character of early metals. Late transition metal enolates are intermediates in aldol and Michael addition processes, -Saegusa oxidations,Heck-type processes, catalytic asymmetric conjugate additions, - and cross coupling of enolate nucleophiles. - ... 

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