Inexpensive Cobalt Salts Catalyzed C-H Activation/Annulation Assisted By Bidentate Traceless Directing Group

Isoquinolinone derivatives are important nitrogen-containing heterocyclic compound which are widely present in natural products and bioactive molecules.In recent years,its extraordinary pharmacological activity in anti-cancer and antihypertensive has drawn great attention.Transition metal-catalyzed direct functionalization of C-H bond has emerged as a practical,atomically economical synthesis method for providing a new approach to the synthesis of isoquinolinone derivatives.Based on previous research in the laboratory,we have designed O-(pyridin-2-ylmethyl)hydroxylamine bidentate guiding group with easily broken N-O bonds.Isoquinolines synthesis is described via cobalt-catalyzed C-H activation/annulation with internal alkynes.In this reaction,the target product was obtained in trifluoroethanol at 100 oC for 10 hours while Co(OAc)2?4H2O was used as the catalyst,Ag OAc was used as the oxidant and Piv OH was used as the additive.In the catalysis process,the O-(pyridin-2-ylmethyl)hydroxylamine guiding group participated in coordination and could be automatically removed after completing the reaction.This operationally simple approach shows a broad substrate scope with 36 isoquinolinones obtained in good to excellent yields.When 7-oxabenzonorbornadiene was used as the coupling reagent,an unexpected five-membered [3+2] cyclization product was obtained.In addition,according to relevant literature reports and experimental studies of the mechanism,a possible reaction course of this reaction is proposed.