Organocatalysis asymmetric Michael reactions

Hayashi, Y., Gotoh, H., Hayashi, T., Shoji, M. (2005). Diphenylprolinol silyl ethers as efficient organocatalysis for the asymmetric Michael reaction of aldehydes and nitroalkenes. Angewandte Chemie International Edition, 44, 4212-4215. 

Even if organocatalysis is a common activation process in biological transformations, this concept has only recently been developed for chemical applications. During the last decade, achiral ureas and thioureas have been used in allylation reactions [146], the Bayhs-Hillman reaction [147] and the Claisen rearrangement [148]. Chiral organocatalysis can be achieved with optically active ureas and thioureas for asymmetric C - C bond-forming reactions such as the Strecker reaction (Sect. 5.1), Mannich reactions (Sect. 5.2), phosphorylation reactions (Sect. 5.3), Michael reactions (Sect. 5.4) and Diels-Alder cyclisations (Sect. 5.6). Finally, deprotonated chiral thioureas were used as chiral bases (Sect. 5.7). 

Figure 1.15 Supramolecular catalysts for organocatalysis (a) Route to catalyst libraries (b) asymmetric nitro-Michael reaction.

Other reviews deal with aldol additions of group 1 and 2 enolates,103 direct catalytic asymmetric aldol reactions catalysed by chiral metal complexes,104 the exploitation of multi-point recognition in catalytic asymmetric aldols,105 and recent progress in asymmetric organocatalysis of aldol, Mannich, Michael, and other reactions.106... 

The asymmetric Michael addition is one of the most frequently studied reactions in asymmetric organocatalysis, and impressive levels of conversion and enantiose-... 

By aiming at BRMs within MBFTs and organocatalysis, this section is limited to a small field of research. Nonetheless, the method is very productive, and the number of interesting examples extends far beyond the number that will be discussed in this section. Therefore, we will start, without further introduction, with the first example by Itoh and coworkers, who reported a proline-catalyzed asymmetric addition reaction for the synthesis of mf-dihydrocomynantheol in 2006 [6]. The reaction commences with activation of methyl vinyl ketone derivative 1 to form the intermediate enamine 4. Simultaneously, the acidic carboxyl group allows activation of the imine 2 and directs the newly formed nucleophile to add stereoselectively on iminium ion 5. The resulting o,p-unsaturated iminium is prone to diastereoselective cyclization by aza-Michael addition of the liberated secondary amine (Scheme 14.1). 

Chiral secondary amines are another important class of privileged functional component in dual organocatalysis that has been widely used in asymmetric catalysis [39]. For example, in 2008, Cordova et al. [40] reported the combinational use of (S)-diphenylprolinol TMS ether (127) and Br0nsted base DABCO (128) as dual organocatalysts to promote the asymmetric domino double Michael addition reaction (nitro-Michael/Michael reaction) of 5-nitropentenoate (125) to a,(i-unsaturated aldehydes (Scheme 43.26), which gave the corresponding nitrogen-,... 

Organocatalysis Continuing efforts to harness the cooperative activity of bifunctional organocatalysts have led to the examinations of chiral calix[4]arenes containing amino phenol stractures and chiral per-6-amino-P-cyclodextrin in the asymmetric sulfa-Michael reactions to cyclic and acylic enones.The preliminary results indicated that further structural modification would be required to allow more efficient asymmetric catalyst systems. 

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... 

Cobb, A.J.A., Shaw, D.M., Longbottom, D.A., Gold, J.B. and Ley, S.V. (2005) Organocatalysis with proline derivatives improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions. Org. Biomol. Chem., 3, 84. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

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. 

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