Total Synthesis of (-)-Fasicularin and (-)-Lepadiformine A Based on Zn-Mediated Allylation of Chiral N-tert-Butanesulfinyl Ketimine

摘要

The stereoselective total synthesis of fasicularin (1) and lepadiformine A (2) is described, which features the utilization of a Zn-mediated allylation of a chiral, aliphatic, N-tert-butanesulfinyl ketimine to construct the amino-substituted quaternary carbon center in good yield and with excellent diastereoselectivity. The azaspirocyclic scaffold was installed sequentially by a Sharp less dihydroxylation and an internal epoxide-opening reaction, and this scaffold was further converted into common intermediate 5. Removing the tosyl (Ts) protecting group of 5 and reductively aminating using Luche's reagent completed the synthesis of (-)-fasicularin (1), while reducing 5 using L-selectride, deprotecting the Ts group, and finishing with an intramolecular amino alcohol cyclocondensation completed the total synthesis of (-)-lepadiformine A (2).