The Development of Sequential Silylcarbocyclization Silicon-Based Cross-Coupling Reactions and Their Application in the Total Synthesis of Isodomoic Acid H
Liu, Jack Hung-Chang
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https://hdl.handle.net/2142/72256
Description
Title
The Development of Sequential Silylcarbocyclization Silicon-Based Cross-Coupling Reactions and Their Application in the Total Synthesis of Isodomoic Acid H
Author(s)
Liu, Jack Hung-Chang
Issue Date
2009
Doctoral Committee Chair(s)
Denmark, Scott E.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Abstract
A sequential rhodium-catalyzed silylcarbocyclization of enynes parlayed with a palladium-catalyzed, silicon-based cross-coupling reaction has been developed. 1,6-Enynes reacted with benzyldimethylsilane in the presence of rhodium catalysts to afford five-membered rings bearing a (Z)-alkylidenylbenzylsilyl group. A variety of substitution patterns and heteroatom substituents were compatible. These alkylidenylsilanes underwent palladium-catalyzed cross-coupling with aryl iodides promoted by tetra-n-butylammonium fluoride, displaying a broad substrate scope. This catalytic system shows a broad compatibility towards substitution patterns, electronic properties, and heteroatoms. All of the cross-coupling reactions proceeded in high yields under very mild conditions and with complete retention of double bond configuration, resulting in densely functionalized 3-(Z)-benzylidenecyclopentanes and analogous heterocycles. This synthetic method was applied to the total synthesis of a marine natural product of the kanoid family, isodomoic acid H. This total synthesis was achieved via a short twelve step longest linear sequence, in which the key transformations include a diastereoselective rhodium-catalyzed carbonylative silylcarbocyclization reaction of a vinylglycine-derived 1,6-enyne, a desilylative iodination reaction with an inversion of double bond configuration, as well as an alkenyl-alkenyl silicon-based cross-coupling reaction uniting the core alkenyl iodide and the side-chain silanol. The mechanistic insight garnered during the investigation of the invertive desilylative iodination reaction enabled the accomplishment of a desilylative iodination reaction with an inversion of double bond configuration, thus opening up a promising synthetic route leading towards the total synthesis of isodomoic acid G, a congener of isodomoic acid H.
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