Nickel-Catalyzed Asymmetric Synthesis of Ambiphilic Secondary Phosphine Oxides

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 P-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 P-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 P-stereogenic compounds.