Transition metal-catalyzed cross-coupling of silicon electrophiles for the synthesis of vinyl and alkyl silanes
Date
2017
Authors
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Publisher
University of Delaware
Abstract
Vinyl and alkyl silanes are important molecules in organic synthesis, medicinal chemistry, and materials chemistry. The ability of vinyl silanes to participate in Hiyama-Denmark cross-coupling, oxidations, and desilylative halogenations make them highly versatile intermediates. Alkyl silanes engage in similar oxidations and Peterson olefinations. The material properties of alkyl silanes are still under exploration, but they display a profound propensity for freezing point depression when compared to hydrocarbon congeners and amplified lipophilicity of bioactive molecules. I sought to develop methods that could synthesize vinyl and alkyl silanes through transition metal catalysis. Prior to this work, there were limited methods to access vinyl silanes from silyl triflates and secondary alkyl silanes from halosilanes and an organometallic nucleophile. ☐ This dissertation describes the discovery and development of transition metal catalyzed methods to form vinyl and alkyl silanes. We have developed a nickel-catalyzed silyl Heck reaction capable of activating silyl triflates with iodide additives. This methodology allows the first access to silyl triflate electrophiles in cross-coupling, greatly expanding the scope and capabilities of the silyl-Heck reaction. ☐ Advancing the utility of transition metal-catalyzed cross-coupling of halosilanes, I was able to develop a high yielding methodology for the synthesis of secondary alkyl silanes from organozinc halides and iodosilanes; formally a silyl-Negishi reaction. This alkylation strategy was then improved upon by the discovery and development of chlorosilane cross-coupling of Grignard reagents. Exploration of this unprecedented chlorosilane cross-coupling revealed that highly sterically hindered secondary alkyl silanes were capable of being accessed with this methodology. Additionally, mechanistic studies suggest against a typical Kumada cross-coupling mechanism and favor the formation of anionic palladium to perform a substitution at the silicon center.
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Keywords
Pure sciences, Alkyl silane, Cross coupling, Silane, Silicon, Transition metal, Vinyl silane