Enantioselectivities screening conditions

Under the standardized screening conditions, WT YqjM displays only about 3% conversion in the model reaction and moderate enantioselectivity (76% ee) in favor of (J )-8a, which indicates that the substrate is not well accepted. Therefore, in order to evolve active and stereoselective YqjM mutants, screening was focused primarily on activity. Accordingly, mutants were identified by automated gas chromatography (GC) and those active above the WT threshold were checked for enantioselectivity. Since this involved the optimization of two distinct catalytic parameters, the quality of each hit was defined by two numbers, namely, % conversion (0-100%) and % ee for the (J )- or (S)-regime, respectively [37]. Then the total impact (TI) was calculated by multiplying the two parameters (Table 5.5). Such a procedure leads to the... 

A novel Ru precursor and a new reaction system had to be found because the classical Ru complexes and conditions for the hydrogenation of C=C bonds did not work. Besides the enantioselectivity, chemo- and cis-selectivity and activity problems (tetrasubstituted C=C) were solved on a very good level. A broad screening of Ru catalysts (partly in collaboration with Solvias) showed that selected Josiphos ligands and DuPhos satisfied the prerequisites (see Table 37.4). 

When from initial experiments, conditions that indicate the enantioselectivity of the system towards a given enantiomer pair or towards a limited series of substances are known, one might optimize their separation. To obtain optimal conditions, the different chemometric techniques used for method optimization in classic chromatographic or electrophoretic separations can also be applied for the chiral ones. Different experimental design approaches, using both screening and response surface designs can be In Reference 331, for... 

Ricci and co-workers introduced a new class of amino- alcohol- based thiourea derivatives, which were easily accessible in a one-step coupling reaction in nearly quanitative yield from the commercially available chiral amino alcohols and 3,5-bis(trifluoromethyl)phenyl isothiocyanate or isocyanate, respectively (Figure 6.45) [307]. The screening of (thio)urea derivatives 137-140 in the enantioselective Friedel-Crafts reaction of indole with trans-P-nitrostyrene at 20 °C in toluene demonstrated (lR,2S)-cis-l-amino-2-indanol-derived thiourea 139 to be the most active catalyst regarding conversion (95% conv./60h) as well as stereoinduction (35% ee), while the canditates 137, 138, and the urea derivative 140 displayed a lower accelerating effect and poorer asymmetric induction (Figure 6.45). The uncatalyzed reference reaction performed under otherwise identical conditions showed 17% conversion in 65 h reaction time. 

After completing his initial intramolecular cycloaddition, Hodgson utilized conditions that had been optimized for the intermolecular cycloaddition of DMAD with simple cyclic carbonyl ylides used by Hashimoto and co-workers (139). Hodgson et al. (140) found that the reaction indeed gave excellent overall chemical yield, but the enantioselectivity dropped to 1%, giving essentially a racemic mixture. It appeared that ee ratios were sensitive to the electronic nature of the dipole. Hodgson chose to screen several binaphthol derived rhodium catalysts of the type developed by McKervey and Pirrung, due in part to the reports of... 

From the 60 catalysts screened in the first round, four members displayed an enantioselectivity >50% (indicated green and red). Five catalysts of the library provided a conversion of >90% under the conditions applied (displayed in red). 

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

Bolm and Bienewald discovered in 1995 that some chiral vanadium (IV)-Schiff base complexes were efficient catalysts (1 mol %) for sulfoxidation [71a]. The catalyst 20 was prepared in situ by reacting VO(acac)2 with the Schiff base of a fJ-aminoalcohol (Scheme 6C.8). Reactions were conveniently performed in air at room temperature by slow addition of 1.1 mol equiv. of aqueous hydrogen peroxide (30%). Under these experimental conditions the reaction of methyl phenyl sulfide gave the corresponding sulfoxide in 94% yield and 70% ee. The best enantioselectivity was obtained in the formation of sulfoxide 21 (85% ee). Many structural analogues of catalyst 20 were screened for their efficacy, but none of... 

By screening solvent and inorganic bases to establish the optimal reaction conditions for dimeric chiral PTCs, a toluenexhloroform (7 3, v/v) solvent system and a 50% aqueous KOH base were found to afford the best enantioselectivity and chemical yield within a reasonable reaction time. As dimeric cinchona-PTCs are very poorly soluble in toluene (one of the popular solvents in asymmetric alkylation), this might act as an obstacle for the catalyst to show its maximum ability. However, the addition of chloroform to toluene provided better results due to an improved solubility of the dimeric PTC. This difference in ability to dissolve the dimeric PTC might be heavily associated not only with the reaction rate but also with the chemical/ optical yield. However, the use of chloroform alone proved to be inadequate as an optimal solvent [10]. 

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