Modular Synthesis of Chiral Phosphine‐Phosphite‐Ligands from Phenolic Precursors: A New Approach to Bidentate Chelate Ligands Exploiting a PO to PC Migration Rearrangement

An efficient and modular approach to bidentate phosphine‐phosphite ligands formally derived from a 6‐alkyl‐2‐phosphanylphenol, a chiral diol and phosphorus trichloride has been developed. In a key step, a borane‐protected phosphinite, prepared from an o‐bromophenol by O‐phosphanylation, is reacted with n‐butyllithium to afford the corresponding ortho‐phosphanylphenol (as the stable borane adduct) through bromine‐lithium exchange and anionic migration rearrangement. Treatment with phosphorus trichloride in the presence of a base and subsequent reaction of the in situ formed dichlorophosphite with a chiral diol (such as TADDOL or BINOL) affords the target P,P ligands in good overall yield (up to 60% over 4 steps). In contrast to an earlier approach, the new methodology is very general and tolerates bulky ortho‐substituents. The reliability of the operationally convenient protocol was demonstrated in the synthesis of a library of 16 new phosphine‐phosphite ligands, starting from different ortho‐alkylphenols. The modular concept opens a rapid access to a broad variety of ligands and might be useful in the search for and structural optimization of suitable ligands for specific chirogenic transition metal‐catalyzed transformations.