Synthesis, Application and Kinetic Studies of Chiral Phosphite‐Oxazoline Palladium Complexes as Active and Selective Catalysts in Intermolecular Heck Reactions

Abstract

AbstractThis study identifies new phosphite‐oxazoline ligands that have been successfully applied in the palladium‐catalyzed intermolecular asymmetric Heck reaction. The design of the new phosphite‐oxazoline ligands derives from a previous successful generation of phosphine‐oxazoline ligands, by replacing the phosphine group with several π‐acceptor biaryl phosphite moieties. With these simple modifications, the new phosphite‐based ligands, unlike previous phosphine‐oxazoline, not only present a modular design with numerous potential phosphite groups available, but they are also air‐stable solids, which can be made in the same number of synthetic steps as the phosphine analogues. The substitution of the phosphine by a biaryl phosphite group extended the range of substrates and triflates sources that can be coupled with regio‐, enantioselectivities and activities comparable to the few best ones reported. In addition, the ligands that provided the best selectivities contained an isopropyl oxazoline moiety instead of the tert‐butyl group found in the related phosphine‐oxazoline ligands, which is made from a much more expensive precursor. In this paper we have also carried out kinetic studies and a Hammett plot analysis to determine the rate determining step of this system in the regime of interest. We suggest a likely explanation for the fast Heck reaction of the phosphite‐oxazoline catalysts.magnified image