Harnessing Dpp-Imine as a Powerful Achiral Cocatalyst to Dramatically Increase the Efficiency and Stereoselectivity in a Magnesium-Mediated Oxa-Michael Reaction.

Abstract

Listen

Translate article

Dpp-imines are classic model substrates for synthetic method studies. Here, we disclose their powerful use as achiral coligands in metal-catalyzed reactions. It is highly interesting to find that the Dpp-imine can not only act as powerful ligand to create excellent chiral pockets with magnesium complexes but also, more importantly, this coligand can dramatically enhance the catalytic ability of the metal catalyst. The underlying reaction mechanism was extensively explored by conducting a series of experiments, including 31P NMR studies of the coordination complex between the Dpp-imine coligand and magnesium complexes, ESI capture results, multiple control experiments, studies and comparison of different coligands, 1H NMR studies on the relationship between the substrate and Dpp-imine coligand, as well as the relationship between the substrate and the full complexes. Furthermore, DFT calculation provided valuable insights in the role of the imine additive and demonstrated that adding the Dpp-imine coligand in the magnesium catalyst can switch the deprotonation/nucleophilic addition steps from a stepwise mechanism to a concerted process during the oxa-cyclization reaction. The crucial factors responsible for the excellent enantioselectivity and enhanced reaction efficiency brought by Dpp-imine have been extracted from the calculation model. These mechanistic experiments and DFT calculation data clearly disclose and prove the powerful and interesting functions of the Dpp-imine coligand, which also direct a novel application of this type of active imine as useful ligands in metal-catalyzed asymmetric reactions.