Copper-bispidine catalyzed aziridination – a new twist in small molecule activation

Copper(I) and in particular (for practical reasons) copper(II) are among the preferred metal centers for metal ion catalyzed aziridination, and bispidine complexes have been shown to lead to efficient catalysts. It is known that the efficiency shows a moderate dependence on the Cu II/I redox potential, and this is used to optimize the catalyst system. The highlight of the present study, however, is that ligands, where a particular tertiary amine is replaced by a secondary amine in the supporting bispidine ligand leads to an up to 1000-fold increase of the catalytic efficiency. This is shown to be due to a deprotonation equilibrium, and the p K a value of the coordinated amine has been determined to around 9.5, which shows that the Cu II center in the particular geometry of the complex leads to a very strong activation of the coordinated secondary amine, and this has important consequences for the activation of the nitrene. Described are copper(I) and copper(II) complexes of a series of tetradentate bispidine ligands together with their structural, spectroscopic and electrochemical properties. These complexes are efficient catalysts for the aziridination of styrene, and the efficiency is shown to be correlated to the Cu II/I redox potential. While variation of the redox potential only leads to relatively small changes of the catalytic properties, it is shown that replacement of the in-plane tertiary amine of the bispidine scaffold by a secondary amine leads to an up to 1000-fold increase of the catalytic efficiency. In contrast, no significant increase of the catalytic performance is observed when the axial tertiary amine is replaced by a secondary amine. The effect of the in-plane substitution of the tertiary amine is shown to be related to a deprotonation at the secondary amine in presence of a base. This is demonstrated with a Cu II acetonitrile complex for which a p K a value in MeCN of approx. 17.5 (corresponding to an approx. p K a value of 9.5 in H 2 O) was determined by spectrophotometric titration. It is proposed that the enhanced catalytic efficiency is due to deprotonation of the amine at the high-valent part of the catalytic cycle. This may lead to a stabilization of the nitrene form, but most important to a drastic improvement of the catalytic performance.