Asymmetric Organocatalyzed Synthesis of α-Aminophosphinates via Thiourea Anion-Binding Catalysis

Thioureas catalyze the reaction of phosphonites with in situ-generated isoquinolinium salts to give C and P-stereogenic alpha-aminophosphinates in high enantioselectivity (up to 96 %) and yield (up to 95 %). Low diastereoselectivity was obtained and this is rationalized in the context of a mechanistic proposal involving anion-binding catalysis of the P-C bond formation step followed by uncatalyzed Arbuzov collapse. The scope of the reaction, including a g-scale example, was demonstrated. P-Stereogenic alpha-aminophosphinates were obtained in high enantioselectivity via anion-binding catalysis with thiourea catalysts, further expanding the range of nucleophiles that can be used in this type of catalysis.+ image