Development of a One-Step Synthesis of oxa-Spirocyclic Diphosphine Ligands Driven by Their Application in the Industrial Synthesis of Sacubitril.

Herein we have developed a highly practical and efficient one-step coupling protocol for the synthesis of chiral spiro diphosphine ligands, especially for the oxa-spiro diphosphine ligands O-SDP, which showed excellent reactivity and diastereoselectivity in the asymmetric hydrogenation of a key intermediate of Sacubitril. It should be noted that the one-step coupling protocol could be operated on a kilogram scale, and the resulting ruthenium catalyst of O-SDP could hydrogenate the key intermediate of Sacubitril on an industrial scale.