Transition Metal-Catalyzed Asymmetric C-P Cross-coupling for Accessing P‑Stereogenic phosphorus ligands

The world is full of chirality. Chiral molecules play an enormous role in medicine, agricultural chemistry and material science. The classical synthetic method of these useful chiral molecules is organic synthesis, more specifically, asymmetric synthesis. Among various asymmetric synthetic strategies, asymmetric catalysis is most effective and attractive. Numerous new opportunities and challenges would emerge with the development of previously underdeveloped catalytic asymmetric reactions.

Asymmetric catalysis is a very broad and exciting field in organic synthesis. The Nobel Prize in Chemistry in 2001 was awarded to William S. Knowles, Ryoji Noyori, and K. Barry Sharpless for asymmetric catalysis with metal catalysts. This year, Benjamin List and David MacMillan are awarded the Nobel Prize in Chemistry 2021 because of asymmetric organocatalysis. The development of efficient chiral catalysts has played an important role in the field of asymmetric catalysis. Compared with other chiral ligands like carbenes, dienes and bisoxazolines, chiral organophosphorus ligands are the most powerful and frequently used in transition metal-catalyzed and organocatalyzed asymmetric reactions. With the exceptionally high demand of P-chiral ligands, it is significant to develop novel methods for achieving these optically pure P‑Stereogenic organophosphorus compounds.

Transition metal-catalyzed enantioselective C-P cross-coupling reactions of secondary phosphine oxides with aryl or alkyl electrophiles are attractive and effective strategies providing convenient access to structurally diversified P-chiral and C-chiral phosphorus compounds. Nevertheless, the catalytic asymmetric P−C cross-coupling reactions are less explored and remain highly challenging, which is probably caused by competitive coordination of excess phosphines substrate to transition metals inhibiting or poisoning the catalyst and eroding the enantioselectivity. Thus, the investigation of novel and efficient catalyst system for driving asymmetric P−C cross-coupling of secondary phosphine oxides with aryl or alkyl electrophiles is of significant demand. The easy accessibility and modular structure of P-chiral organophosphorus products will offer us opportunity to solve other challenging and unprecedented asymmetric catalysis in fundamental study. In this way, asymmetric C-P Cross-coupling for accessing P‑Stereogenic organophosphorus molecules will contribute significantly to asymmetric catalysts which are bringing the greatest benefit to humankind.