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

Abstract

Abstract 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.