Cu(ii)-mediated tautomerization for the pyrazole-nitrile coupling reaction†
Abstract
This study investigates the mechanism of prototropic tautomerization in metal-bound asymmetric pyrazole (R-PzH) ligands during Cu(II)-mediated PzH-MeCN coupling reactions. Intrinsic prototropic tautomerization of metal-bound ligands has not been previously documented. Various new bis-pyrazolylamidino Cu(II) complexes, [Cu(R-Pz(HNC(Me)))2(ClO4)2], from the coupling reaction, and tetrakis pyrazole Cu(II) complexes, [Cu(R-PzH)4(ClO4)2], with symmetric and asymmetric C-monosubstituted R-PzH ligands were synthesized and characterized. Kinetic UV-vis studies revealed slower coupling rates with asymmetric R-PzH ligands, further reduced with increasing substituent size due to steric hindrance impeding tautomerization. Structural analysis showed preferential binding of asymmetric 3(5)-R-PzH to Cu(II) ions at the C5 position of PzH, requiring a tautomeric shift to the C3 position for the subsequent coupling reaction. DFT calculations confirmed the greater stability of the C5-tautomeric [Cu(R-PzH)4(ClO4)2] complexes over their C3 counterparts, explaining the rate discrepancies. A mechanism involving counteranion-mediated proton transfer during tautomerization is proposed to account for coupling product formation.