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Abstract Amides are among the most important and ubiquitous functional groups in organic chemistry and process development. In this Practical Synthetic Procedure, a protocol for the Suzuki–Miyaura cross-coupling of amides by selective N–C(O) bond activation catalyzed by commercially available, air- and moisture-stable palladium/N-heterocyclic carbene (NHC) complexes is described. The procedure described involves [Pd(IPr)(cin)Cl] [IPr = 2,6-(diisopropylphenyl)imidazol-2-ylidene, cin = cinnamyl] at 0.10 mol% at room temperature and is performed on decagram scale. Furthermore, a procedure for the synthesis of amide starting materials is accomplished via selective N-tert-butoxycarbonylation, which is the preferred method over N-acylation. The present protocol carries advantages of operational simplicity, commercial availability of catalysts, and excellent conversions at low catalyst loadings. The method is generally useful for activation of N–C(O) amide bonds in a broad spectrum of amide precursors. The protocol should facilitate the implementation of amide cross-coupling reactions. 

A Pd-PEPPSI-catalyzed (Pd = Palladium, PEPPSI = pyridine-enhanced precatalyst preparation stabilization and initiation) Suzuki-Miyaura cross-coupling of aryl esters via selective C–O cleavage at room temperature is reported. The developed catalyst system displays broad substrate scope with respect to both components under practical ambient reaction conditions using readily-available, cheap, modular, air- and moisturestable Pd-NHC precatalyst (NHC = N-heterocyclic carbene). The use of water proved crucial for achieving high reactivity in this coupling. The catalyst system represents the mildest conditions for the Suzuki-Miyaura cross-coupling of aryl esters reported to date. The protocol also allowed for achieving TON >1,000 (TON = turnover number) in the Suzuki-Miyaura ester coupling for the first time.