<i>P</i>‑Stereogenic β‑Aminophosphines: Preparation and Applications in Enantioselective Organocatalysis

The synthesis of stereodefined β-aminophosphines having both carbon- and phosphorus-based chirality centers is described. The method involves resolution of a mixture of β-aminophosphine oxide diastereomers accessed by ring-opening of an amino alcohol-derived cyclic sulfamidate. A stereospecific, borane-promoted reduction of β-aminophosphine oxides, which occurs under mild conditions and with inversion of configuration at phosphorus, is a key step in this process. The products obtained are new building blocks for the synthesis of <i>P</i>-chiral ligands and organocatalysts. In a proof-of-concept application in organocatalysis, the diastereomeric <i>P</i>-chiral β-aminophosphine-based bifunctional thioureas displayed significantly different activities in the Morita–Baylis–Hillman reaction of methyl acrylate with benzaldehyde derivatives