High-Throughput Screening of Chiral Ligands and Activators

7 High-Throughput Screening of Chiral Ligands and Activators 

The activation effect was really observed in random screening of chiral ligand/ activator combinations. Enantioselectivity of the reaction is also increased by matched eombination of diol ligands and nitrogen activators. The replacement of 3- and 3 -positions with bulky phenyl groups, 3,3 -diphenyl-l,l -bi-2-naphthol (L ), may further prevent the aggregation of binolato-Zn and increase the enantioselectivity, because of their steric demand to provide (S)-l-phenylpropanol in up to 65% ee and quantitative yields. 

On the basis of the results collected from the primary combinatorial library, we then create the next generation library of diimines (activators) with 12 members 

AH library members significantly activate the L -Zn complex and produce 1-phenylpropanol in higher yields and enantioselectivities than those obtained by only using the ligands themselves. The steric hindrance of the chiral activators is crucial, and hence the activator A provides the best results. The reaction catalyzed by the best combination L /A is further optimized by tuning the lower reaction temperature. (5)-l-phenylpropanol is obtained in 99% ee and quantitative yield (Eq. (7.28)). Even if 2 mol % of L /A is used for the reaction, (5)-phe-nylpropanol can be obtained in 97% ee and 100% yield. 

The best combination of chiral ligands and activators can easily be found out in an efficient way by super high throughput screening (SHTS) employing CO-HPLC with achiral stationary phase for affording the most enantioselective activated catalyst to give excellent yields and enantioselectivities. 

---