Dual Metalation in a Two-Dimensional Covalent Organic Framework for Photocatalytic C-N Cross-Coupling Reactions

Covalent organic frameworks (COFs) are promisinghosts in heterogeneous catalysis. Herein, we report a dual metalationstrategy in a single two-dimensional-COF TpBpy for performing avariety of C-N cross-coupling reactions. [Ir(ppy)2(CH3CN)2]PF6[ppy = 2-phenylpyridine], containing two labile CH3CN groups, andNiCl2are used as iridium and nickel-metal precursors, respectively, forpostsynthetic decoration of the TpBpy COF. Moving from thetraditional approach, we focus on the COF-backbone host for visible-light-mediated nickel-catalyzed C-N coupling reactions. Thecontrolled metalation and recyclability without deactivation of bothcatalytic centers are unique with respect to previously reportedcoupling strategies. We performed various photoluminescence,electrochemical, kinetic, and Hammett correlation studies to under-stand the salient features of the catalyst and reaction mechanism. Furthermore, theoretical calculations delineated the feasibility ofelectron transfer from the Ir center to the Ni center inside the confined pore of the TpBpy COF. The dual metal anchoring withinthe COF backbone prevented nickel-black formation. The developed protocol enables selective and reproducible coupling of adiverse range of amines (aryl, heteroaryl, and alkyl), carbamides, and sulfonamides with electron-rich, neutral, and poor (hetero) aryliodides up to 94% isolated yield. The reaction can also be performed on a gram scale. Furthermore, to establish the practicalimplementation of this approach, we have applied the synthetic strategy for the late-stage diversification of the derivatives ofibuprofen, naproxen, gemfibrozil, helional, and amino acids. The methodology could also be applied to synthesize pharmacophoreN,5-diphenyloxazol-2-amine and Food and Drug Administration-approved drugs, includingflufenamic acid,flibanserin, andtripelennamine.

Automated summary

This study presents a dual metalation strategy using a COF TpBpy for C-N cross-coupling reactions. The strategy demonstrates controlled metalation, recyclability, and visible-light-mediated catalysis. Experimental and theoretical studies provide insights into the catalyst and reaction mechanism.