Calixarene-supported Pd–NHC complexes as efficient catalysts for scalable Suzuki–Miyaura cross-couplings

Benzyloxycalix[8]arene is reported as a suitable macrocyclic support for Pd-NHC complexes, which catalyses C-C cross-coupling reactions with high efficiency. Resulting PEPPSI-derived complexes, issued from a scalable synthetic procedure avoiding any tedious purification, are indeed used as heterogeneous catalysts in ethanol to promote the Suzuki-Miyaura coupling between various aryl halides and aryl boronic acids (or esters). Optimisation of the reaction conditions allowed the use of only a slight excess of base (K3PO4, 1.2 equivalents) and boronic acid (1.1 equivalents), and these conditions were also successfully applied to a large scale benchmark reaction (1 mole of substrate) using a low palladium loading (0.001 mol %). Furthermore, target products were easily isolated after simple filtration procedures with low residual Pd traces (down to 3 ppm) thanks to the insoluble nature of the macrocyclic catalyst in ethanol, thus proving the usefulness of this support to promote coupling reactions relevant to the fine chemical industry.