Stereoselective synthesis Nozaki-Hiyama-Kishi

Scheme 3.13 Protecting-group directed stereoselective intramolecular Nozaki-Hiyama-Kishi reaction. A concise and efficient total synthesis of amophidinolactone A.

Mohapatra DK, Das PP, Pattanayak R, Gayatri G, Sastry GN, Yadav, JS. Protecting-group directed stereoselective intramolecular Nozaki-Hiyama-Kishi reactions a concise and efficient synthesis of Amphidinolactone A. Eur. J. Org. Chem. 2010 4775 784. 

Pilli RA, Victor MM. Total synthesis of (—)-Decarestrictine D through a stereoselective intramolecular Nozaki-Hiyama-Kishi reaction. Tetrahedron Lett. 1998 39 4421 1424. 

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. 

This chapter will review the literature up to the end of 2011 on the stereoselective Nozaki-Hiyama-Kishi reaction and applications in natural product synthesis. The transformation of the NHK reaction from using stoichiometric to catalytic amounts of chromium will be addressed initially then the diastereoselective NHK, followed by the enantioselective version (with an emphasis on the different classes of chiral ligands that have been employed in a wide variety of carbon-carbon bond forming processes), and finally, selected examples of the application of the NHK reaction to natural product synthesis will be described. 

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