Enantioselective Preparation of P -Chirogenic SPOs from Phosphinous Acid Boranes Applied in Non-Atropoisomeric Biarylphosphine and Derivative Syntheses

An efficient enantioselective synthesis of P-chirogenic phosphine(oxide)s with a non-atropoisomeric biaryl substituent or bridge was reported. The method was based on two key steps. First, the enantioselective synthesis of P-chirogenic o-halogenophenylphosphine oxides was achieved with complete retention of configuration at the P atom, by one-pot reaction of secondary phosphine oxides (SPOs) with benzyne, in situ generated from 1,2-dibromo- or -diiodobenzene. The P-chirogenic SPOs were enantioselectively prepared by successive acid hydrolysis of aminophosphine boranes derived from (+)- or (-)-ephedrine and then decomplexation of the phosphinous acid borane intermediate by CF₃SO₃H or HBF₄. The high enantioselectivity of the SPO preparation was herein improved by neutralization at low temperature after acid decomplexation of the phosphinous acid borane. Second, the arylation of the P-chirogenic o-halogenophenylphosphine oxides into o-biaryl derivatives was enantioselectively achieved using a Pd-catalyzed cross-coupling reactions with boron reagents. The stereoselective deoxygenation of biarylphosphine oxides was demonstrated using a mixture of polymethylhydrosiloxane and titanium(IV)isopropoxide as a reductive agent. At the end, the homocoupling of o-iodophenylphosphine oxide into non-atropoisomeric P-chirogenic diphosphine oxide borne by a simple biphenyl bridge was demonstrated using the Ullmann reaction in the presence of copper. Indeed, this enantioselective synthesis of P-chirogenic o-halogenophenylphosphine oxides from SPOs opens up an efficient new way to afford numerous classes of chiral phosphorus compounds, notably bearing a non-atropoisomeric biaryl substituent or bridge.