Time-dependent enantiodivergent synthesis via sequential kinetic resolution

• Published in: Nature chemistry 2020-09, Vol.12 (9), p.838-844
• Main Authors: Tu, Hang-Fei, Yang, Pusu, Lin, Zi-Hua, Zheng, Chao, You, Shu-Li
• Format: Article
• Language: English
• Subjects: 639/638/403/933; 639/638/549/933; 639/638/549/972; 639/638/77/883; Absolute configuration; Analytical Chemistry; Biochemistry; Catalysts; Chemical synthesis; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Configurations; Enantiomers; Inorganic Chemistry; Materials science; Organic Chemistry; Permutations; Physical Chemistry; Reaction time; Reaction time task; Substitution reactions; Time dependence
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/s41557-020-0489-1

The preparation of both enantiomers of chiral molecules is among the most fundamental tasks in organic synthesis, medicinal chemistry and materials science. Achieving this goal typically requires reversing the absolute configuration of the chiral component employed in the reaction system that is being used. The task becomes challenging when the natural source of the chiral component is not available in both configurations. Herein, we report a time-dependent enantiodivergent synthesis, in which an Ir-catalysed allylic substitution reaction uses one catalyst sequentially to promote two kinetic resolution reactions, enabling the synthesis of both enantiomers of the product using the same enantiomer of a chiral catalyst. The appropriate permutation of individual reaction rates is essential for the isolation of the chiral products in opposite configurations with high enantiopurity when quenched at different reaction times. This work provides an alternative solution for the preparation of both enantiomers of chiral molecules. Access to both enantiomers of a chiral target compound typically relies on reversing the absolute configuration of the chiral component in the reaction system that is used to make them. A time-dependent enantiodivergent synthesis is reported in which the same enantiomer of a chiral catalyst can give both enantiomers of the product, depending on the reaction time.