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

This manuscript is dedicated to Professor David A. Evans.

Abstract

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

Key words

transfer hydrogenation - chiral phosphoric acid - continuous flow - enantioselectivity - heterocycles

Publikationsverlauf

Eingereicht: 11. März 2023

Angenommen nach Revision: 03. Mai 2023

Accepted Manuscript online:
03. Mai 2023

Artikel online veröffentlicht:
29. Juni 2023

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