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.