Aldol and α-Amination Reactions with Proline-Functionalized Reactors

Significance

Proline-functionalized silica 1 was synthesized and the packed-bed reactor A was developed by filling with 1. Continuous-flow aldol reaction of cyclohexanone 2 with 4-nitrobenzaldehyde 3 proceeded at 5 mL min^-¹ flow rate to give 4 with 4:1 dr (anti/syn) and 78% ee of the anti isomer. The α-amination reaction of isovaleraldehyde 5 with dibenzylazodicarboxylate 6 was also performed using the reactor A at 25 mL min^-¹ flow rate to give 7 with >95% conversion, 55% ee, and 3.60 mmol h^-¹ mmol_cat ^-¹ productivity.