Novel Pd(PN,S)-complexes: Highly active catalysts designed for asymmetric allylic etherification

Article abstract of DOI:10.1016/j.mcat.2021.111763

Six novel thioether-aminophosphine type ligands with a general formula (Ar¹)₂PN(R¹)CHR²(CH₂)_nCH(R³)SAr² has been synthesized. The modular structure of the ligands and the new methodologies developed for their preparation enabled the systematic variation of their bridge length (n = 0 or 1), the substitution pattern of the backbone (R², R³ = H or Me) as well as the P-, N- and S-substituents (Ar¹ = Ph or 3,5-Me₂C₆H₃, R¹ = Et or iPr and Ar² = Ph, 4-MeC₆H₄, or 4-MeOC₆H₄, respectively). The ligands proved to be effective in Pd-catalyzed asymmetric allylic etherification reactions providing the products in high yields (up to 95%) and with good enantioselectivities (up to 86%) using unprecedentedly low (0.2 mol%) loadings of the chiral Pd-catalyst. Based on these findings, a new scalable protocol has been developed for the preparation of chiral allylic ethers. Furthermore, the Pd(II) coordination chemistry of the ligands was thoroughly investigated by 1D and 2D NMR methods as well as by X-ray crystallography with special attention to the conformation of the chelate ring and the stereoselectivity of the sulfur coordination. Based on these studies, the main factors determining activity and selectivity of the catalytic system have been identified.