Mechanistic insights into an NH4OAc-promoted imine dance in Rh-catalysed multicomponent double C–H annulations through an N-retention/exchange dual channel

• Published in: Chemical science (Cambridge) 2023-11, Vol.14 (46), p.13446-13452
• Main Authors: Li, Shiqing, Lv, Shihai, Yang, Yanyan, Zhu, Peiyan, Zhao, Dongbing, Ming-Hua Zeng
• Format: Article
• Language: English
• Subjects: Alkynes; Ammonium acetate; Chemical reactions; Chemistry; Controllability; Crystallography; Dance; Diketones; Exchanging; Hydrazines; Iodine; Organic chemistry
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d3sc03861k

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 14N/15N editing in one shot has been developed. Through a combination of isotopic-labeling (2H, 18O, and 15N) 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 15N 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.