Steric evaluation of Pyox ligands for asymmetric intermolecular Heck-Matsuda reaction

Abstract

A structure selectivity relationship was established by systematically increasing the steric of the ligands from phenyl substituent to mesityl on the pyridine ring of Pyox and isopropyl to tert-butyl group on the oxazoline ring. The ligand 6MesPyoxsBu bearing a sterically demanding mesityl group at position 6 of the pyridine ring showed optimum catalytic activity for Heck-Matsuda desymmetrization reaction of non-activated cyclopentene using Pd(tfa)2 as the catalyst. A wide range of arenediazonium salts bearing electronically distinct substituents was evaluated in Heck-Matsuda coupling, which resulted in good to excellent isolated yields (67–92 %), excellent enantio- and diastereoselectivity (up to 96 % ee, >20:1 dr).