Remote Construction of Diverse Heteropolycycles via 1,4-Pd or 1,4/1,5-Pd Migration-Mediated Intermolecular Double C–H Annulation

Abstract

Although 1,4-Pd migration has been widely used for the functionalization of remote C−H bonds, intermolecular double C−H annulation via this strategy remains elusive. Furthermore, catalytic reactions involving 1,5-Pd migration are scarce due to competitive reductive elimination pathway. Herein, we report an intermolecular double C–H annulation of N-(2-bromophenyl)-2-phenylacrylamides with 1,n-diynes mediated by 1,4-Pd or sequential 1,4/1,5-Pd migrations. The reaction proceeds through sequential Heck cyclization, alkyl-to-aryl 1,4-Pd migration (or alkyl-to-aryl 1,4-Pd migration followed by aryl-to-aryl 1,5-Pd migration), dual alkyne insertion, and C–H activation, providing efficient access to both indolinone-substituted tricyclic frameworks and tetracyclic indolinones. The method exhibits excellent regioselectivity, and preliminary mechanistic studies support the proposed pathway.

Keywords

1,4-Pd migration / 1,5-Pd migration / C–H activation / Domino reactions / Annulation / Acrylamides / 1,n-Diynes / Heteropolycycles

RIGHTS & PERMISSIONS

2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH