Mastering the Potential of Well-defined ML 1 L 2 Species in Asymmetric Catalysis through Ligand Immobilization (ML het L hom ). Use in Highly Enantioselective Pd-catalyzed Spiroannulation

Abstract

Catalytic complexes involving different monodentate ligands coordinated to the same metal center offer considerable interest towards the development of new processes and the improvement of the characteristics of known ones. However, one of the major drawbacks in using mixtures of monodentate ligands in asymmetric metal catalysis lies in the difficulty of controlling the formation of active species containing both of the desired ligands coordinated at the same time to the metal center (ML1L2). Herein, we present a straightforward methodology to overcome this long-standing major limitation. Thus, we demonstrate that the formation of well-defined ML1L2 species can be attained by combining an immobilized ligand and a homogeneous ligand. This concept has been successfully applied to a synthetically relevant Pd-catalyzed [3+2] spiroannulation. The use of a polystyrene supported chiral binaphthyl-based phosphoramidite in combination with an achiral cheap biphenyl monophosphoramidite led to the sole formation of highly enantioselective active species containing both ligands coordinated to Pd, as demonstrated by gel-phase, high resolution 31P NMR. In addition, we have also studied the continuous flow spiroannulation, which further demonstrated that the reaction occurs in the heterogenous phase. The advantages associated to the use of well-defined PdLhetLhom in catalysis are further demonstrated in asymmetric allylic alkylation reactions, illustrating the potential of this methodology in asymmetric catalysis.