One-Pot Multisubstrate Screening for Asymmetric Catalysis Enabled by ¹⁹F NMR-Based Simultaneous Chiral Analysis.

Area of Science:

• Organic Chemistry
• Catalysis
• Analytical Chemistry

Background:

• Exploring diverse chemical space is crucial for asymmetric synthesis.
• Optimization of chiral processes across multiple substrates is resource-intensive.
• High-throughput screening (HTS) is promising but hampered by complex mixture analysis.

Purpose of the Study:

• To develop a rapid multisubstrate screening workflow for simultaneous chiral analysis.
• To overcome limitations of traditional chromatography-based analysis in complex mixtures.
• To accelerate the evaluation of structure-selectivity relationships in asymmetric synthesis.

Main Methods:

• Utilized 19F NMR spectroscopy for simultaneous chiral analysis.
• Employed an NMR-shifting cobalt reagent to induce dynamic peak shifts and splitting.
• Applied the method to ruthenium-catalyzed asymmetric reductive amination of ketones.

Main Results:

• Accurately determined yields and enantiomeric excesses for up to 21 substrates in a single reaction.
• Achieved precise chiral analysis through 19F NMR peak dynamics.
• Demonstrated a significant acceleration in evaluating structure-selectivity relationships.

Conclusions:

• The presented workflow enables rapid and accurate chiral analysis of complex reaction mixtures.
• This 19F NMR-based method facilitates mechanistic insights into enantio-determining processes.
• The approach significantly enhances efficiency in asymmetric synthesis optimization.