Synthesis of jiadifenin using Mizoroki–Heck and Tsuji–Trost reactions

Abstract

The formal synthesis of jiadifenin, which has potent neurotrophic activity, was accomplished using intramolecular Mizoroki–Heck reaction and tandem Tsuji–Trost cyclization/lactonization reaction as key steps. Intramolecular Mizoroki–Heck reaction was employed for the construction of the A ring moiety accompanied with the formation of C9 quaternary center, which was dramatically promoted by protic solvent. Tandem Tsuji–Trost cyclization/lactonization reaction was applied to the successive cyclization of the BC ring system to elaborate under conditions, Pd(OAc)2, (±)-BINAP, and LiOAc in t-BuOH, leading to Theodorakis's intermediate followed by a few functionalizations.