Palladium-Catalyzed Modular Assembly of P-Stereogenic and Axially Chiral Phosphinooxazoles (PHOX) Ligands by C–P Bond Cleavage/Intermolecular C(sp²)–H Bond Functionalization

Abstract

Chiral P,N-ligands are of great interest and importance in the fields of metal-catalyzed enantioselective transformations and have found numerous applications spanning drug and polymer synthesis. Here, modular assembly of diverse P-stereogenic and axially chiral phosphinooxazoles ligands is achieved through palladium-catalyzed asymmetric cleavage of C–P bond/intermolecular C–H bond functionalization in high atroposelectivities and diastereoselectivities of up to >99% ee and >25:1 dr. This protocol features broad substrate scope and provides an avenue for facile construction of new P-stereogenic and axially chiral phosphinooxazoles ligands directly from the phosphonium salts and benzoxazoles/benzothiazoles. Evaluation of the synthesized P-stereogenic and axially chiral phosphinooxazoles ligands in two model catalytic asymmetric reactions illustrates the potential of our strategy to access valuable chiral molecules.

P-Stereogenic Phosphorus Ligands in Asymmetric Catalysis

“…From 2001 to 2023, a great number of P-stereogenic phosphorus ligands with structural diversity have been designed, synthesized, and applied in numerous catalytic asymmetric reactions. This remarkable advancement is largely ascribed to the development of many efficient methods for the synthesis of P-stereogenic organophosphorus compounds including novel chiral phosphorus ligands. − ,,,,− In addition, breakthrough results obtained by the use of P-stereogenic phosphorus ligands have encouraged researchers to devote their efforts to this area.…”

“…Figure presents all the P-stereogenic monophosphorus ligands reported from 2001 to 2023. ,,,,,,,,,,− …”

“…Most of these ligands possess functional groups that are capable of forming cyclic metal complexes by coordination. Typically, the ligands with nitrogen functional groups such as oxazolines ( L92 , L95 , LalithPhos, MaxPHOX, , L133 , Mengphos, and L141 ), pyridyl groups ( L109 and BoQPhos), a dimethylamino group ( L91 ), an imino group ( L93 ), a pyrrole group ( L119 ), a triazole group ( L131 ), and a benzoxazole group ( L136 ) have been used in the Ir-catalyzed asymmetric hydrogenation of alkenes or the Pd-catalyzed C–C bond-forming reactions. Other P,N-ligands ( L101 , L129 , L137 , L138 , L139 , and L140 ) are also expected to show characteristic reactivities in asymmetric metal catalysis.…”

Dithiophosphinylation of Allenyl Acetates: Access to 1,2-Bis(diphenylphosphino)ethane-Type Bidentate Ligands

“…However, to the best of our knowledge, the direct transition-metal-free diphosphinylation of allenes to achieve DPPE-type ligands remains elusive. Given the great importance of DPPE-type ligands in synthetic organic chemistry and our interests for constructing phosphine ligands, herein, we report the straightforward dithiophosphinylation of readily available allenyl acetates to give 1,2-bisphosphinoethane derivatives with high yields and regioselectivity (Scheme b). This protocol features a broad substrate scope and mild conditions avoiding the use of transition metals or air-sensitive sources of phosphorus.…”