Importance of monodentate mono-ligand designs in developing N-stabilized Pd catalysts for efficient ambient temperature C[sbnd]C coupling: Donor strengths and steric features

Abstract

Unfriendly temperature profiles and costs of carbon coupling catalysis, which pose challenge to both synthetic organic chemists as well as industrial applicability, motivated our design of new monodentate N-donors as support ligands for the purpose of constructing ambient temperature precatalysts that are molecularly close to the hypothetical active forms. Therefore, a series of sterically varied monodentate N-donor imidazoles (1–7) and oxazoles (8–9) have been synthesized and their N-donor strengths, which were estimated as pKas, are systematically varied from 0.9 to 8.5 by substituent variations. Eleven target mono-ligand complexes (1-PdCl2MeCN – 9-PdCl2MeCN, 6-PdCl2PhCN and 7-PdCl2PhCN) and six trans-bis-ligand complexes (12-PdCl2, 22-PdCl2, 32-PdCl2, 62-PdCl2, 12-Pd(OAc)2 and 22-Pd(OAc)2) were isolated and catalytically studied along with PdI2(PPh3)2. Results of coupling reactions, which were conducted both via in situ ‘Pd(II) salt + ligand’ approach and by use of the precatalysts, show that the mono-ligand precatalyst designs (1-PdCl2MeCN – 9-PdCl2MeCN, 6-PdCl2PhCN and 7-PdCl2PhCN) represent a true catalyst improvement initiative among the phosphine-free catalyst community; i.e. yields approaching 100% (TOF ≈ 2000) at 0.2 mol % catalyst loading, 45 °C and within 15 min. On the other hand, the complexes with trans-bis-ligand coordination were inactive at ambient temperatures. Therefore, it was concluded that coordinative saturation, which results from implementing two or more ligand equivalents or use of polydentate ligands on palladium, should be strongly discouraged. Such saturation necessitates the undesirable and avoidable high temperature necessities, long reflux durations and needlessly high catalyst loadings. Correlation between catalyst activity and donor strengths or steric properties were analysed leading to important conclusions. The catalyst design also supported coupling of activated aryl chlorides from 60 °C while Heck coupling activities were observed only at the early minutes of reactions.