CD-Monitored HTS of Chiral Catalysts

Significance

High-throughput screening (HTS) of chiral catalysts was performed with flow-CD detector. A combinatorial library of chiral diamine-copper catalysts (12 members) was prepared on polystyrene support (beads). Catalytic efficiency was examined for the Henry reaction of 2-nitrobenz­aldehyde with nitromethane and evaluated by the asymmetric conversion yield (ACY) value. Signal intensity obtained via analysis using the CD detector provided the ACY value in which the information of both asymmetric induction ability and catalytic activity were combined in one signal data. Catalyst D1 was identified to be an effective lead catalyst for the asymmetric Henry reaction. Through the lead optimization, L*-CuCl was found to promote the Henry reaction with high enantioselectivity and high catalytic activity (8 examples with 6 aldehydes).