Samarium(II) iodide promoted 8-endo ketyl-olefin couplings: New methods in total synthesis

The samarium(II) iodide (SmI₂)-promoted 8-endo ketyl-olefin coupling has been successfully applied to the synthesis of natural products. The required condition that the olefin be substituted with an electron-withdrawing group or a conjugated group was used to advantage to install functional groups required in the target natural products. For example, the total synthesis of isoschizandrin featured, as a key step, an 8-endo ketyl-olefin coupling utilizing an aryl-substituted olefin. The aryl group provides a portion of the biaryl carbon framework of isoschizandrin. Furthermore, the high oxophilicity of the tightly-associated Sm(III) metal center produced upon reduction of the carbonyl group generated noteworthy stereochemical consequences, leading to the desired stereochemical outcome in the samarium(II) iodide-promoted transformation.; Similarly, the total synthesis of steganone utilized a butenolide as the olefin component to simultaneously generate the five- and eight-membered ring of the fused 8-5 ring system present in the natural product. The direct product of the samarium(II) iodide-promoted cyclization in this case produced a novel congener that was closely related to congeners exhibiting in vivo and in vitro inhibition of tubulin polymerization.; During studies directed toward the synthesis of a third natural product, spartidienedione, an olefin doubly activated by a silyl group and an allylic acetate was utilized. This mode of activition yielded an alkenyl silane contained within the product eight-membered ring that can be elaborated by a variety of transformations.