Three-Component Bisannulation for the Synthesis of Trifluoromethylated Tetracyclic Aza-Aromatics through Six C(sp³)−F Bond Cleavage and Four C−N Bond Formation

Qing-Dong Wang,*^a,b Ya-Wen Wang,^a Ting Xie,^a Yan-Ying Cui,^a Mengtao Ma,^c Zhi-Liang Shen,^a and Xue-Qiang Chu*^a

^a Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.

^b School of Pharmacy, Yancheng Teachers University, Yancheng 224007, China.

^c Department of Chemistry and Materials Science, College of Science, Nanjing Forestry University, Nanjing 210037, China.

Abstract: An unprecedented and expeditious tandem bisannulation of polyfluoroalkylated tetralones with benzamidines to access various fluoroalkyl tetracyclic [1,3]-diazepines through multiple C-N bond formation and C(sp³)-F bond cleavage is reported. The process features high regio/chemoselectivities, broad substrate scope, good functional group tolerance, procedural simplicity, mild reaction conditions, and scale-up synthesis. Mechanistic studies showed that the distinctive fluorine-effect of polyfluoroalkyl tetralone plays a vital role for the aza-tetracycle construction.

J. Org. Chem. 2021, 86, 8236-8247. (Impact factor: 4.35)

论文链接：https://pubs.acs.org/doi/10.1021/acs.joc.1c00695.