Convergent Synthesis of Tetradentate Aminopyridine C-H Oxidation Catalysts

Controlling the oxidation of unactivated C-(sp³)-H bonds through supramolecular catalyst-substrate interactions has recently enabled site-selective transformations previously considered inaccessible. However, progress has been hampered by lengthy linear syntheses of supramolecular catalysts. Here we present a convergent strategy that directly cross-couples preformed tetradentate aminopyridine ligands with recognition motifs, streamlining access to functional catalysts. Using this approach, we prepared four catalysts, two featuring resorcin[4]-arene (RS) and two bearing calix[4]-arene (CX) units, for substrate recognition using the solvophobic effect in 2,2,2-trifluoroethanol. This convergent synthesis reduces the longest linear sequence from 5 steps to 2 steps (starting from the recognition motif) by shifting from a linear, catalyst-specific synthesis to a modular platform that allows rapid assembly of catalyst libraries using premade, interchangeable building blocks.