Access To P-Chiral Phosphine Oxides Enabled By Palladium/Xiao-Phos Catalytic System

P-chiral phosphines have been found to have wide spectrum of practical applications in various fields,however,the lack of concise and effective synthetic methods inhibits it to continue their early promising applications.Despite tremendous efforts have been devoted to develop asymmetric catalysis reactions for their preparation over the past decades,the realization of distinct strategies and successful application of it to the versatile construction of important P-chiral phosphines remains an ongoing challenge in chemical synthesis.This dissertation focuses on the palladium/Xiao-Phos catalytic system,which serves as a new reactivity platform for the construction of P-chiral tertiary phosphine oxides and further expands the application scope of the Sadphos ligand.By virtue of this reactivity platform,the enantioselective P–C cross-coupling strategy was achieved by using of secondary phosphine oxides?SPOs?and aryl bromides,which provides a rapid access to highly enantioenriched P-chiral tertiary phosphine oxides.Due to the relatively weak oxidative addition rate of aryl bromides,the competitive coordination between SPO and the palladium is of priority,which largely ensures the high enantioselectivity of the reaction.The method has mild reaction conditions,wide reaction partners and good application prospect.In particular,the enantioenriched tertiary methylphosphine oxides obtained by this method provides a convenient method for modifying the branched chain of aromatic ring of DIPAMP ligands.Further exploration of this catalytic system lead to the development of the highly selective hydrophosphinylation of alkynes.SPOs and alkynes can be coupled to furnish P-chiral alkenylphosphine oxides in high chemo-,regio-,and enantioselectivities.The enantioenriched SPO can also be recovered in the kinetic resolution system.The subsequent synthetic transformations of the two P-chiral scaffolds have shown good flexibility and practicability.In addition,based on some specific experimental results,we preliminarily determine that the insertion of alkynes undergoes the hydropalladation process,and that the reaction may undergo the same intermediate transition state as in the asymmetric P–C cross-coupling reaction.Preliminary mechanism studies showed that the reactivity platform was based on the combination of SPO and the Pd/Xiao-Phos chiral monomeric species to generate the active intermediate,which is equivalent in the form of putative R₂?OH?P-Pd intermediate or its Pd-H species tautomer.The hydrogen-bond interactions between the sulfinamide NH and the oxygen of the SPO should be invoked to account for the observed high enantioselectivity.