P-chiral Ligands

P-chiral ligands (i.e. ligands where the chirality resides on the phosphorus atoms) can offer significant advantages over their C-chiral (i.e. chirality on the carbon skeleton) cousins.

This is due to the proximity of the stereogenic phosphorus atoms to the “metal pocket” of the ligand thus allowing maximum stereoinduction in the catalysed reaction. (See Lipkowitz et al. J. Am. Chem. Soc. 2002, 124, 14255-14267)

The potential of P-chiral phosphorus ligands inducing high enantioselectivity in catalytic asymmetric reactions is well understood having been established in the literature across a broad range of transformations including hydrogenation, transfer hydrogenation, hydroformylation, hydrosilylation, vinylation, isomerisation etc.

To date however, - with the notable exceptions of DiPAMP (Monsanto) and “Trichickenfootphos” (Pfizer) - the considerable synthetic difficulties associated with making these P-chiral compounds has mitigated against their use in anything other than laboratory scale reactions.