Synthesis of nordihydroguaiaretic acid derivatives via suzuki and stille cross-coupling reactions and subsequent raney nickel desulfurization and reduction

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Ladd, James Michael
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Middle Tennessee State University
The predictability of selectivity in organopalladium chemistry employed to generate carbon-carbon bonds between polyhalogenated heteroaromatic compounds and their cross-coupling partners allow for efficient production of NDGA derivatives. Suzuki couplings between tetrabromo thiophene and arylboronic acids reliably generate substrates for Stille carbon-carbon bond forming reactions. Several methods for desulfurization and reduction of tetra-substituted thiophenes have been published, and a number of these methods were evaluated toward producing the desired end products. Raney
nickel under an atmosphere of hydrogen gas in a Parr hydrogenator, highly activated Raney nickel in alcohol, and nickel boride generated in-situ from nickel chloride and sodium borohydride in a number
of solvent systems were each tested en route to manufacturing substituted NDGA. The primary focus of this research is the synthesis of NDGA derivatives from tetrabromo thiophene.
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Desulfurization, NDGA, Nordihydroquaiaretic, Raney, Stille, Suzuki