Chapter 5 Samarium(II) promoted ketyl olefin cyclizations applied to the total syntheses of (−)-steganone and (+)-isoschizandrin

Abstract

This chapter details the examination process utilized to study the use of samarium (II) iodide in the construction of carbocycles and heterocycles utilizing ketyl-olefin cyclizations. Samarium diiodide is usually featured as a mild, chemoselective reagent for simple functional group transformations employing complex substrates. Therefore, the flexibility introduced in the 8-endo cyclization by varying the olefin substitution can be applied to the construction of many eight-member ring-containing natural products, creating the rings and installing the attendant functionality stereoselectively in a single synthetic operation. Overall, the syntheses of (–)-steganone and ( + )-isoschizandrin illustrate the potential for the samarium (II) iodide-promoted reductive coupling to achieve rapid and efficient access to the dibenzocyclooctadiene lignans. A stereocontrolled 8-endo ketyl-olefin-coupling produces ( + )-isoschizandrin in fine yield with excellent stereo- and regioselectivity. Additionally, this method allows the direct construction of the 8–5 fused ring system of (–)-steganone without the need for multiple functional group manipulations. Steganone is the only diastereomer possible that allows planar alignment of the ketone carbonyl with the neighboring arene ring system. The difficulties associated with constructing the biaryl moiety as a single atropisomer early in the synthesis lies within the arene substitution pattern.