Liu Li, Jiang Qi, Tang Long, Liu Chao, Wang Yanzhao, Wu Fanhong, Wu Jingjing
School of Chemical and Environmental Engineering and Shanghai Engineering Research Center of Green Fluoropharmaceutical Technology, Shanghai Institute of Technology, Shanghai 201418, P. R. China.
Org Lett. 2024 Dec 20;26(50):10833-10839. doi: 10.1021/acs.orglett.4c03914. Epub 2024 Dec 10.
The construction of chiral tetrasubstituted α-fluoro-α-cyano carbonyl compounds remains a key challenge in synthetic organic chemistry because of their popularity in multiple disciplines. In this paper, we report the copper-catalyzed asymmetric fluorinated tertiary radical cyanation reaction of cyclic α-iodo-α-fluoroindanones with TMSCN to achieve chiral nitriles with carbon-fluorine quaternary stereogenic centers. Thus, an array of optically active tetrasubstituted monofluoroacyl nitriles were synthesized with high reaction efficiency and excellent enantioselectivities (up to 91% yield, 99% ee). Moreover, mechanistic investigations, including experiments, were conducted to clarify the reaction pathway and stereochemical outcomes.
