Enantioselective Synthesis of Versatile Stereogenic-at-P(V) Building Blocks via Hydrogen-Bond-Donor Catalysis

Abstract

The stereoselective synthesis of molecules bearing stereogenic phosphorus(V) centers represents an enduring challenge in organic chemistry. While stereospecific nucleophilic substitution at P(V) provides a general strategy for elaborating optically active P(V) compounds, existing methods for accessing the requisite chiral building blocks rely almost entirely on diastereocontrol using chiral auxiliaries. Catalytic, enantioselective methods for the synthesis of synthetically versatile stereogenic P(V) building blocks offer an alternative approach to stereogenic-at-P(V) targets without requiring stoichiometric quantities of chiral controlling elements. Herein, we report an enantioselective hydrogen-bond-donor-catalyzed synthesis of chlorophosphonamidates, and the development of these products as versatile chiral P(V) building blocks. We demonstrate that chlorophosphonamidates possess two leaving groups that can be displaced sequentially and stereospecifically to access a wide variety of stereogenic-at-P(V) compounds featuring diverse substitution patterns.