Catalyst-driven enantioselective

On the basis of the observed stereoinduction trend, the addition of HCN took place over the diaminocyclohexane portion of the catalyst away from the amino acid and amide unit. The last hypothesis led to the prediction that a more sterically demanding amino acid or amide unit (Figure 6.14) could additionally favor the cyanide attack compared to the less bulky diaminocyclohexane unit and thus making the Schiff base catalyst more enantioselective in Strecker reactions of aldimines and ketimines. To evaluate this perspechve, the authors performed a model-(mechanism-) driven systematic structure optimizations by stepwise modification of the amide, the amino acid, and the (thio)urea unit of catalyst 42 and examined these derivatives of 42 (lmol% loading ) in the model Strecker reaction (toluene ... 

Dynamic kinetic resolution (DKR) is an extension to the kinetic resolution process, in which an enantioselective catalyst is usually used in tandem with a chemoselective catalyst. The chemoselective catalyst is used to racemize the starting material of the kinetic resolution process whilst leaving the product unchanged. As a consequence, the enantioselective catalyst is constantly supplied with fresh fast-reacting enantiomer so that the process can be driven to theoretical yields of up to 100 %. There are special cases where the starting material spontaneously racemizes under the reaction conditions and so a second catalyst is not required. 

Very recently further optimization was achieved on the basis of rational mechanism-driven optimization (for this mechanistic study [12], see the corresponding section below). The resulting, further improved catalyst 10b was found to be superior to 9 and 10a, and is the most enantioselective Strecker catalyst yet prepared [12]. Starting from both aliphatic and aromatic aldimines, excellent enantioselectivity in the range 96-99.3% ee was obtained even in the presence of only 1 mol% 10b. An overview of the excellent enantioselectivity obtained with 10b, and comparison with ee values obtained in the presence of catalyst 10a, are given in Scheme... 

A 3D-structure of the substrate-catalyst complex, which was supported by molecular modeling, revealed that the large group of the imine is directed away from the catalyst. This complex of the catalyst with the Z imine, and a solution structure of the organocatalyst, are shown in Figure 5.1 [12]. This explains the broad substrate tolerance which is independent of steric or electronic properties. A further important hypothesis is that addition of HCN occurs over the diaminocyclohexane framework in 10a this led to the prediction that a more bulky amino acid/amide portion should give a further improved catalyst. This conclusion led to (model-driven) optimization which resulted in the improved and highly enantioselective Strecker catalyst 10b (for preparative results with this catalyst see Scheme 5.8 and related text) [12]. 

The Michael reaction is known to be driven by basic catalysts, and accordingly, the surface OH and sites of these oxide crystals are expected to trigger the reaction. Although both NAP-MgO and NA-MgO possess defined shapes and the same average concentrations of surface OH groups, a possible rationale for the higher rate of reaction by NAP-MgO is the presence of more surface Mg (Lewis acid) ions (20%)." The acid-base interactions of the Mg + ions (Lewis acid) of NAP-MgO and the basic chiral auxiliary may also influence the enantioselectivity. 

Very recently, driven by the curiosity of how DNA induces enantioselectivity, Sugiyama and co-workers performed an intramolecular AFC alkylation with a DNA-based hybrid catalyst (Scheme 6.41). In their studies, an elemental binding model was proposed based on their experimental results. These investigations show promise for understanding relationships between the helical chirality of DNA and the enantioselectivity of the chemical reaction. 

Asymmetric transfer hydrogenation (ATH) reactions of 2-substituted a-alko gr-p-ketophosphonates (602) driven by dynamic kinetic resolution, afforded the corresponding 2-substituted a-alko gr-p-hydroxyphos-phonates (603) with excellent levels of diastereo- and enantioselectivity (Scheme 175). The reactions have been promoted by using chiral ruthenium catalyst (604) and a 0.2 1 mixture of formic acid and triethylamine as the hydrogen source and solvent. ... 

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