Bifunctional Bronsted bases

Br0nsted Base-Derived Thiourea Catalysts 353 Chiral Bifunctional Bronsted Base Thiourea Catalyst... 

CHIRAL BRONSTED BASE-LEWIS ACID BIFUNCTIONAL CATALYSIS... 

Trost s group reported direct catalytic enantioselective aldol reaction of unmodified ketones using dinuclear Zn complex 21 [Eq. (13.10)]. This reaction is noteworthy because products from linear aliphatic aldehydes were also obtained in reasonable chemical yields and enantioselectivity, in addition to secondary and tertiary alkyl-substituted aldehydes. Primary alkyl-substituted aldehydes are normally problematic substrates for direct aldol reaction because self-aldol condensation of the aldehydes complicates the reaction. Bifunctional Zn catalysis 22 was proposed, in which one Zn atom acts as a Lewis acid to activate an aldehyde and the other Zn-alkoxide acts as a Bronsted base to generate a Zn-enolate. The... 

Snapper and Hoveyda reported a catalytic enantioselective Strecker reaction of aldimines using peptide-based chiral titanium complex [Eq. (13.11)]. Rapid and combinatorial tuning of the catalyst structure is possible in their approach. Based on kinetic studies, bifunctional transition state model 24 was proposed, in which titanium acts as a Lewis acid to activate an imine and an amide carbonyl oxygen acts as a Bronsted base to deprotonate HCN. Related catalyst is also effective in an enantioselective epoxide opening by cyanide "... 

Finally in Chapters 11-13, some of the more recent discoveries that have led to a renaissance in the field of organocatalysis are described. Included in this section are the development of chiral Brdnsted acids and Lewis acidic metals bearing the conjugate base of the Bronsted acids as the ligands and the chiral bifunctional acid-base catalysts. 

This reaction encompasses a number of interesting features (general Brpnsted acid/Bronsted-based catalysis, bifunctional catalysis, enantioselective organoca-talysis, very short hydrogen bonds, similarity to serine protease mechanism, oxyanion hole), and we were able to obtain a complete set of DFT-based data for the entire reaction path, from the starting catalyst-substrate complex to the product complex. 

Mg-Al mixed oxides obtained by thermal decomposition of anionic clays of hydrotalcite structure, present acidic or basic surface properties depending on their chemical composition [1]. These materials contain the metal components in close interaction thereby promoting bifunctional reactions that are catalyzed by Bronsted base-Lewis acid pairs. Among others, hydrotalcite-derived mixed oxides promote aldol condensations [2], alkylations [3] and alcohol eliminations reactions [1]. In particular, we have reported that Mg-Al mixed oxides efficiently catalyze the gas-phase self-condensation of acetone to a,P-unsaturated ketones such as mesityl oxides and isophorone [4]. Unfortunately, in coupling reactions like aldol condensations, basic catalysts are often deactivated either by the presence of byproducts such as water in the gas phase or by coke build up through secondary side reactions. Deactivation has traditionally limited the potential of solid basic catalysts to replace environmentally problematic and corrosive liquid bases. However, few works in the literature deal with the deactivation of solid bases under reaction conditions. Studies relating the concerted and sequential pathways required in the deactivation mechanism with the acid-base properties of the catalyst surface are specially lacking. 

Bronsted Base/Brensted Acid Bifunctional Catalysts... 

Taking the advantage of the reactivity of alkylideneindolones, Bencivenni and Bartoli developed the nitrocyclopropanation of oxindoles (Scheme 10.15) [21]. The reaction of 1-bromonitromethane (47) with 17c was catalyzed by the bifunctional Bronsted acid-Lewis base cinchona derivative IX. The reaction required 1 equiv of Na2C03 to trap the bromhydric acid released during the last cyclization step. The reaction started with Michael addition of the nitromethane, which was followed by intramolecular alkylation to afford the spirocyclic nitropropanes 48. 

The proposed mechanism presents the nucleophile undergoing a formal Bronsted base interachon with the guanidine catalyst, thus activating the hydro-cyanate for addition to the stabilized electrophile. In comparison to bifunctional catalysts, the guanidines are basic enough to activate and stabiUze both nucleophile and electrophile without assistance from other types of hydrogen-bond interachons. 

The synthetic utility of the bifunctional catalysts in various organic transformations with chiral cyclohexane-diamine derived thioureas was established through the works of Jacobsen, Takemoto, Johnston, Li, Wang, and Tsogoeva. In the last decade, asymmetric conjugate-type reactions have become popular with cinchona alkaloid derived thioureas. The next section presents non-traditional asymmetric reactions of nitroolefins, enones, imines, and cycloadditions to highlight the role of chiral Bronsted base derived thiourea catalysts. 

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