（来源：康龙化成）
转自：康龙化成
Light-Driven Crystallization-Induced Dynamic Resolution of Amines
Jonathan M. Meinhardt 1, Diane D. Kim 1, Emily J. Wu 1, Philip R. D. Murray1, Daniel P. Walker 2, and Robert R. Knowles*1
1 Department of Chemistry, Princetonb University, Princeton, New Jersey 08544, United States
2 Synthetic Molecule Design and Development, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, United States
—J. Am. Chem. Soc, 2025, DOI: 10.1021/jacs.5c07676
Recommended by Yuquan Liu_PT
KEY WORDS:Photo chemistry, Dynamic Resolution (反应类型),amines(底物), chiral amines(产物)
ABSTRACT:The authors reported a method for the dynamic resolution of racemic amines enabled by catalytic photoredox-mediated racemization coupled to in situ diastereomeric crystallization. In this design, anexcited-state iridium chromophore and an achiral thiol cocatalyst mediate the racemization of α-chiral amines under mild, redox-neutral conditions. In the presence of commercially available chiral resolving acids, the desired amine enantiomer is continually precipitated from solution as an insoluble diastereomeric salt. They demonstrated the utility of this method across several structurally distinct families of secondary and tertiary amines with high yields and high levels of enantioselectivity. Given the widespread importance of α-stereogenicamines in the synthesis of fine chemicals, they anticipated that this approach may find further applications that streamline the preparation of these valuable chiral compounds.
Previous Work
This Work
Kinetic resolution development and CIDR optimization
Substrate scope
Stereoinversion experiment and reaction scaleup
Prof. Robert R. Knowleset al have developed a platform for light-driven crystallization-induced dynamic resolution of α-chiral amines which combines the selectivity of diastereomeric crystallization in conjunction with catalyticphotoredox-mediated amine racemization.They demonstrate that this method is applicable across secondary and tertiary amines of significant structural diversity, spanning examples from several classes of medicinally relevant amines. They anticipate that the results presented herein may find additional applications that streamline the preparation of enantioenriched amines, both in the context of chiral amine building blocks as well as in more complex molecular architectures containing amine stereocenters. Moreover, they hope that this work will form the basis for additional advances in CIDR designs, further expanding the impact of this technology.
