Total Synthesis of (+)-Cylindricine C Using an Organocatalytic Michael Reaction

Significance

A total synthesis of (+)-cylindricine C (1) using an organocatalytic asymmetric Michael reaction has been developed. Addition of imine 2 to dienone 3 in the presence of 10 mol% of TaDiAS (tartrate-derived diammonium salt) 4 and Cs₂CO₃ provides intermediate 5 in good yield and enantioselectivity. Subsequent tandem cyclization mediated by camphersulfonic acid and MgCl₂ gives tricyclic compound 6 in moderate yield and diastereoselectivity. Additional functional group interconversions complete the synthesis of natural product 1 in six overall steps.