Hemilabile Diamidophosphite-Thioether Ligands with a β-Hydroxy Sulfide Backbone: Palladium(II) Complexes and Asymmetric Allylic Substitution

Abstract

A series of structurally diverse diamidophosphite-sulfides were synthesized from 1,2-thioether alcohols. With respect to Pd(II), these hemilabile ligands showed the ability to form both P,S-chelates and complexes with two ligands connected to the metal P-monodentately. The structures of the ligands and complexes were confirmed by two-dimensional (2D) NMR spectroscopy and single-crystal X-ray diffraction. These stereoselectors provided up to 98% ee in the Pd-catalyzed asymmetric allylic substitution of (E)-1,3-diphenylallyl acetate with C- and N-nucleophiles and up to 78% ee in the Pd-mediated allylic alkylation of cinnamyl acetate with β-ketoesters. Furthermore, up to 71% ee was achieved in the rare reaction between 2-(diethoxyphosphoryl)-1-phenylallyl acetate and aniline. The effects of the structural parameters, reaction conditions, and ligand-to-metal ratio on the catalytic results are discussed. Due to the ability of the ligands to form structurally different catalytic species, a pronounced dependence of the asymmetric induction on the ligand-to-metal ratio is shown.

TADDOL-based P,S-bidentate phosphoramidite ligands in palladium-catalyzed asymmetric allylic substitution

“…This is in good agreement with the statement that the measurement of enantiomeric excess as a function of the L /M molar ratio should be an important experiment upon testing chiral heterobidentate ligands. 21 (iii) In the allylic alkylation of cinnamyl substrates 12a and 12b , where achieving a high asymmetric induction is a formidable task, 10 f – h ,19 c ee values of up to 90–94% for both enantiomers of product 14 were obtained. (iv) In such challenging asymmetric allylic substitution reactions as the dearomatization of pyrrole 17 and the amination of phosphonate 19 , ligands L5b and L3a are comparable in terms of catalytic results to the most efficient diphosphines, Segphos and SKP, respectively, and superior to some privileged chiral inducers, namely Difluorphos, BINAP, SDP and Trost ligand.…”