Asymmetric Transfer Hydrogenation of Heterocyclic Compounds in Continuous Flow Using an Immobilized Chiral Phosphoric Acid as the Catalyst

This manuscript describes transfer hydrogenation of bicyclic nitrogen containing heterocyclic compounds using immobilized chiral phosphoric acid (R)-PS-AdTRIP catalyst 3a in batch and continuous flow. It was discovered that significant improvement in enantioselectivities was achieved in continuous flow with a fluidized bed reactor packed with (R)-PS-AdTRIP when the flow rate was increased from 0.2 mL/min to 2.0-2.5 mL/min. The optimized continuous flow conditions consistently provided 4-6% ee higher selectivity than transfer hydrogenation in batch with 2 mol% of (R)-PS-AdTRIP (3a) and were used to generate multiple chiral products with the same fluidized bed reactor.