Catalytic Aldol–Cyclization Cascade of 3‑Isothiocyanato Oxindoles with α‑Ketophosphonates for the Enantioselective Synthesis of β‑Amino-α-hydroxyphosphonates

A cascade aldol–cyclization reaction between 3-isothiocyanato oxindoles and α-ketophosphonates has been developed for the synthesis of β-amino-α-hydroxyphosphonate derivatives. Catalyzed by a quinine-based tertiary amino-thiourea derivative, this reaction delivers 2-thioxooxazolidinyl phosphonates based on a spirooxindole scaffold bearing two contiguous quaternary stereogenic centers in high yields with excellent diastereo- (up to >20:1 dr) and enantioselectivities (up to >99:1 er).本研究开发了一种3-异硫氰酸根取代氧化吲哚（3-isothiocyanato oxindoles）与α-酮膦酸酯（α-ketophosphonates）之间的级联羟醛-环化反应，用于β-氨基-α-羟基膦酸酯衍生物的合成。该反应以奎宁衍生的叔胺-硫脲衍生物为催化剂，可得到带有两个连续季碳立体中心的螺环氧化吲哚（spirooxindole）骨架修饰的2-硫代恶唑烷基膦酸酯（2-thioxooxazolidinyl phosphonates）产物，反应收率优异，同时展现出极佳的非对映选择性（最高可达>20:1 dr）与对映选择性（最高可达>99:1 er）。