Ultra-High-Throughput Mapping of the Chemical Space of Asymmetric Catalysis Enables Accelerated Reaction Discovery

ABSTRACT: The discovery of highly enantioselective catalysts and elucidating their generality face great challenges due to the complex multidimensional chemical space of asymmetric catalysis and inefficient screening methods. Here, we develop a general strategy for ultra-high-throughput mapping the chemical space of asymmetric catalysis by escaping the time-consuming chiral chromatography separation. The ultrafast (~1000 reactions/day) and accurate (median error < ±1%) analysis of enantiomeric excess are achieved through the ion mobility-mass spectrometry combines with the diastereoisomerization strategy. A workflow for accelerated asymmetric reaction screening is established and verified by mapping the large-scale chemical space of more than 1600 reactions of α-asymmetric alkylation of aldehyde with organocatalysis and photocatalysis. Importantly, a class of high-enantioselectivity primary amine organocatalysts of 1,2-diphenylethane-1,2-diamine-based sulfonamides is discovered by the accelerated screening, and the mechanism for high-selectivity is demonstrated by computational chemistry. This study provides a practical and robust solution for large-scale screening and discovery of asymmetric reactions.

ORGANISM(S): Acyrthosiphon Pisum

SUBMITTER: Suming Chen  

PROVIDER: PXD045953 | iProX | Wed Oct 18 00:00:00 BST 2023

REPOSITORIES: iProX