Cp*Co(III)-Catalyzed C(8)-Nucleophilic Cascade Cyclization of Quinoline N-Oxide with 1,6-Enyne

The C(8)-selective nucleophilic cascade cyclization of quinoline N-oxide with easily derived 1,6-enyne from phenol derivatives is demonstrated. A variety of quinoline N-oxide and alkynes are discovered to be suitable for producing a library of quinoline N-oxide tethered cis-hydrobenzofurans with high yields and excellent functional group tolerance. The utility of the protocol has been accomplished by post-synthetic modification of the cyclized product. The mechanistic studies indicate a base-assisted internal electrophilic-type substitution (BIES)-type pathway for C-H bond activation, and electrospray ionization mass spectrometry (ESI-MS) analysis of the stoichiometric reaction confirmed the formation of a key five-membered cobaltacycle.

Automated summary

This study demonstrates the C(8)-selective nucleophilic cascade cyclization of quinoline N-oxide with easily derived 1,6-enyne from phenol derivatives. Various quinoline N-oxide and alkynes are found to be suitable for producing a library of quinoline N-oxide tethered cis-hydrobenzofurans with high yields and excellent functional group tolerance. The utility of the protocol has been achieved through post-synthetic modification of the cyclized product. Mechanistic studies reveal a base-assisted internal electrophilic-type substitution (BIES)-type pathway for C-H bond activation, and electrospray ionization mass spectrometry (ESI-MS) analysis confirms the formation of a key five-membered cobaltacycle.