Modular <i>P</i>‑Chirogenic Phosphine-Sulfide Ligands: Clear Evidence for Both Electronic Effect and <i>P</i>‑Chirality Driving Enantioselectivity in Palladium-Catalyzed Allylations

Using the ephedrine methodology, modular stereoselective syntheses of a new class of <i>P</i>-chirogenic phosphines bearing a sulfur-chelating arm (P*,S-hybrid ligand) are described. A first series of syntheses based on a Fries-like rearrangement of <i>P</i>-chirogenic phosphinite-boranes, which are prepared from 2-bromobenzyl or 2-bromophenethyl alcohol and are mediated by metal–halide exchange, have been performed. This rearrangement affords phosphine-boranes stereospecifically with an <i>o</i>-hydroxy­alkylphenyl substituent. The latter residue is subsequently converted into a sulfur-containing group. In a second series, the stereoselective syntheses were achieved according to a new strategy involving a reaction of a thiophenyllithium reagent with a <i>P</i>-chirogenic phosphinite. The X-ray structures of the P*,S ligands and their palladium complexes allow us to address the absolute configuration at both the phosphorus and sulfur centers. The P*,S ligands were used in palladium-catalyzed allylic alkylations, as tests, affording asymmetric inductions up to 96% ee. Computer modeling corroborates the regio- and enantioselectivity of the Pd-catalyzed allylations and the low influence of the substituent carried by the sulfur moiety, particularly when the chelate forms a six-membered ring with the metal