P-chirogenic phosphorus compounds by stereoselective Pd-catalysed arylation of phosphoramidites

The phosphorus stereocentre, present in a diversity of compounds ranging from phosphonates to phosphines, plays a crucial role in various fields, in particular catalysis, materials science, agrochemistry and drug development. The unique structural and stereochemical features of intrinsically homochiral phosphorus units form the incentive for major current efforts towards developing stereoselective synthesis methodology of P-chirogenic compounds. Despite advances in metal-catalysed C–P bond formation, generating homochiral phosphorus stereocentres remains challenging. Here we present an efficient and flexible method for the synthesis of various classes of P-chirogenic compounds through the functionalization of phosphonamidates with excellent stereoselectivity. Key to this is an asymmetric C–P cross-coupling reaction between phosphoramidites and aryl halides with axial-to-central transfer of chirality and the use of 1,1′-bi-2-naphthol as an inexpensive chiral auxiliary. Preliminary mechanistic studies revealed the formation of an unexplored chiral amino–phosphonium intermediate. This transformation sets the stage for ready access to P-chirogenic phosphinates, phosphine oxides and phosphines. General and efficient methodologies for the construction of homochiral phosphorus stereocentres are sought-after. Now, merging Pd-catalysed cross-coupling with phosphorus arylation of phosphoramidites provides access to a broad array of asymmetric P-compounds by axial-to-central chirality transfer from BINOL.