P‑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 P-chiral ligands and organocatalysts. In a proof-of-concept application in organocatalysis, the diastereomeric P-chiral β-aminophosphine-based bifunctional thioureas displayed significantly different activities in the Morita–Baylis–Hillman reaction of methyl acrylate with benzaldehyde derivatives.

本研究报道了同时兼具碳手性中心与磷手性中心的立体规整β-氨基膦(β-aminophosphines)的合成方法。该方法通过对氨基醇衍生的环状磺酰胺酯(cyclic sulfamidate)开环得到的β-氨基膦氧化物(β-aminophosphine oxide)非对映异构体混合物进行拆分来实现。其中，在温和条件下发生、且伴随磷中心构型翻转的硼烷(borane)促进的立体专一性β-氨基膦氧化物还原反应，是该流程的关键步骤。所得产物为合成磷手性配体与有机催化剂的新型合成砌块。在有机催化的概念验证应用中，基于非对映异构磷手性β-氨基膦的双功能硫脲催化剂，在丙烯酸甲酯与苯甲醛衍生物的Morita–Baylis–Hillman反应中展现出显著不同的催化活性。