Modular synthesis of chiral phosphine-phosphite-ligands from phenolic precursors: A new approach to bidentate chelate ligands exploiting a P-O to P-C 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.