The Development of Sequential Silylcarbocyclization Silicon-Based Cross-Coupling Reactions and Their Application in the Total Synthesis of Isodomoic Acid H

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Liu, Jack Hung-Chang

Contributors dc:contributor

• Denmark, Scott E.

• Chemistry, Organic

Identifier

(UMI)AAI3392195

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/72256