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Mechanistic insights into an NH 4 OAc-promoted imine dance in Rh-catalysed multicomponent double C-H annulations through an N-retention/exchange dual channel.

Shiqing LiShihai LvYanyan YangPeiyan ZhuDongbing ZhaoMing-Hua Zeng
Published in: Chemical science (2023)
Developing new and understanding multicomponent reactions (MCRs) is an appealing but challenging task. Herein, Rh(iii)-catalyzed multicomponent double C-H annulations of cyclic diimines (or diketones and acetone), alkynes, and ammonium acetate to assemble functionalized 1,1'-biisoquinolines and C-bridged 1,1'-bisisoquinolines with controllable 14 N/ 15 N editing in one shot has been developed. Through a combination of isotopic-labeling ( 2 H, 18 O, and 15 N) experiments, crystallography, and time-dependent ESI-MS, the reaction process was studied in detail. Ammonium acetate accounts for two rounds of Hofmann elimination and iminization, thus leading to an unprecedented imine dance, cyclic imine → N -alkenyl imine → NH imine. The N -alkenyl imine can immediately guide a C-H annulation (N-retention channel), and some of it is converted into NH-imine to trigger another annulation (N-exchange channel). The channels and 15 N ratios can be regulated by the reaction mode and acidity. Moreover, the resulting 1,1'-biisoquinolines are a privileged ligand scaffold which is exemplified herein by a hydrazine-iodine exchange reaction to form drug-like benzo[ c ]cinnolines.
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