Nickel-Catalyzed Asymmetric Synthesis of Ambiphilic Secondary Phosphine Oxides

Abstract

The synthesis of ambiphilic compounds, which possess both strong nucleophilic and electrophilic functional groups, presents a significant challenge due to their propensity to self-react, forming oligomers or polymers. We have successfully achieved the nickel-catalyzed asymmetric synthesis of ambiphilic <i>P</i>-stereogenic alkenyl secondary phosphine oxides from a tailored primary phosphine oxide by leveraging their controversial stability and reactivity. This method demonstrates remarkable tolerance toward a wide range of unactivated alkynes, including those derived from natural products and medicinally relevant molecules, thus providing a universal synthon for <i>P</i>-stereogenic phosphines with high enantioselectivity and regioselectivity. The ambiphilic product exhibits interesting orthogonal reactivities with both nucleophiles and electrophiles and can be easily converted to a variety of medicinally relevant <i>P</i>-stereogenic compounds.