Macrocyclization via remote meta-selective C-H olefination using a practical indolyl template

The synthesis of macrocyclic compounds with different sizes and linkages remains a great challenge via transition metal-catalysed intramolecular C-H activation. Herein, we disclose an efficient macrocyclization strategy via Pd-catalysed remote meta-C-H olefination using a practical indolyl template. This approach was successfully employed to access macrolides and coumarins. In addition, the intermolecular meta-C-H olefination also worked well and was exemplified by the synthesis of antitumor drug belinostat from inexpensive and readily available benzenesulfonyl chloride. Notably, catalytic copper acetate and molecular oxygen were used in place of silver salts as oxidants. Furthermore, for the first time, the formation of a macrocyclophane cyclopalladated intermediate was detected through in situ Fourier-transform infrared monitoring experiments and ESI-MS.

Automated summary

An efficient macrocyclization strategy via Pd-catalysed remote meta-C-H olefination using an indolyl template is disclosed, enabling the synthesis of macrocyclic compounds such as macrolides and coumarins. The intermolecular meta-C-H olefination is also demonstrated, achieving the synthesis of the antitumor drug belinostat from readily available benzenesulfonyl chloride. Furthermore, the formation of a macrocyclophane cyclopalladated intermediate is detected through in situ Fourier-transform infrared monitoring experiments and ESI-MS.