Asymmetric Catalytic Double Michael Additions for the Synthesis of Spirooxindoles

Asymmetric cascade double Michael additions to construct 2′‐substituted 3,3′‐spirooxindoles by using a chiral guanidine organocatalyst has been developed. A series of spirooxindole derivatives containing dihydrofuran or pyrrolidine subunits were obtained with good to excellent diastereo‐ and enantioselectivities. The method showed great tolerance of a number of aromatic and aliphatic alkynones. The strategy gave access to the asymmetric synthesis of (−)‐salacin for the first time. Michael additions go chiral: The title reaction was realized by using guanidine catalyst. The present working model functions well for a variety of aryl‐ and alkyl‐substituted alkynes as well as substituted oxindoles with good enantioselectivities (up to 97.5:2.5 er). The first catalytic asymmetric synthesis of (−)‐salacin is also reported. The desired spirooxindoles are found as core structures in numerous bioactive compounds.