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.
ABSTRACT
Chiral monodentate biaryl phosphines (MOPs) have attracted intense attention as chiral ligands over the past decades. However, the creation of structurally diverse chiral MOPs with both P- and axial chirality is still in high demand but challenging. Here, we show a distinct strategy for diversity-oriented synthesis of structurally diverse MOPs containing both P- and axial chirality enabled by enantioselective C-P bond cleavage. The key chiral PdII intermediates, generated through the stereoselective oxidative addition of C-P bond, could be trapped by alkynes, R3Si-Bpin, diboron esters or reduced by H2O/B2pin2, leading to enantioenriched structurally diverse MOPs in excellent diastereo- and enantioselectivities. Based on the outstanding properties of the parent scaffolds, the P- and axially chiral monodentate biaryl phosphines serve as excellent catalysts in asymmetric [3 + 2] annulation of MBH carbonate affording the chiral functionalized bicyclic imide.
ABSTRACT
The transition-metal-catalyzed C-P bond cleavage has emerged as a powerful tool for the formation of both C-C and C-P bond. However, the transition-metal-catalyzed stereoselective cleavage of C-P bond is still undeveloped. Herein, we report a palladium-catalyzed stereoselective cleavage of C-P bond for the construction of P-stereogenic phosphines and stereogenic axis. This protocol enables the quick synthesis of atropisomers bearing a P-stereogenic center in high yields, diastereo- and enantioselectivities of up to 98 % ee, >25 : 1 dr. The product is able to serve as chiral catalyst in phosphine catalyzed [3+2] cycloaddition of allenoates to imines, showing the great potential of the present methodology.