Nozaki-Hiyama-Kishi coupling strategy

We selected the natural product thyrsiferol as an ideal target to test our ideas. Its total synthesis was envisioned to proceed as illustrated in the Scheme 28. The successful coupling between aldehyde 84 and vinyl iodide 82 via a Nozaki-Hiyama-Kishi (NHK) reaction [66] had been demonstrated previously [29]. We therefore sought to model our final steps after precedence presented by Forsyth for the union of these two fragments. The focus of our synthetic strategy centered around the stereoselective synthesis of the ABC framework (84) of thyrsiferol (1) as a scaffold to validate the scope of the Cp2TiCl reaction with epoxides toward the assembly of Q-C-glycosides and cyclic ethers. 

The first total synthesis of pinnatoxin A (104) was completed by Kishi s group in 1998 [67,68]. Their synthetic strategy is shown in Scheme 13. They planned to make the seven-membered iminium ring at the last stage, and the key macrocyclization was carried out by an intramolecular Diels-Alder reaction. Fragments 138-141 were coupled using the Nozaki-Hiyama-Kishi reaction, Juba coupling reaction etc. 

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