Pd-PEPPSI catalysts bearing N-heterocyclic carbene ligands derived from caffeine and theophylline for Mizoroki–Heck and C(sp2)–H arylation reactions

The activity of three Pd-PEPPSI catalyst precursors bearing N-heterocyclic carbene (NHC) ligands derived from caffeine and theophylline was tested in Mizoroki–Heck reactions between styrene and five different aryl bromides bearing electron-donating or withdrawing substituents. Moderate to excellent conversions (44–98%) were achieved within 3 h at 100°C with K2CO3 as the base and 1 mol% of catalyst in a green water/isopropanol mixture under a normal atmosphere. Electron-withdrawing groups favored the reaction and led to the highest yields of stilbene products (up to 85% after chromatographic purification). The activity of the three [PdX2(NHC)(Py)] complexes (X = Cl, I) was also probed in the C(sp2)–H arylation of two heterocyclic substrates using the same set of five representative aryl bromides. Experimental conditions were further optimized on a model reaction (1 mol% of catalyst in DMA at 120°C for 4 h with KOAc as the base). Gratifyingly, 1-methyl-2-pyrrolecarboxaldehyde afforded high conversions (59–99%) and yields of isolated products (49–85%), with the best results obtained again under the influence of electron-withdrawing substituents. When a more challenging substrate, viz., 3,5-dimethylisoxazole was used, modest to satisfactory conversions (41–80%) and yields (30–69%) could still be reached with the best catalyst for each reaction. The structural properties of the complexes under investigation were compared using X-ray crystallography and Hirshfeld surface analysis.