Developing Asymmetric Gold Redox Catalysis for Challenging Chemical Transformations

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Project Summary/Abstract The proposed project’s goal is to develop organic synthesis methodologies for potential applications in biochemistry and medicinal science to solve important problems (optimizing API production process and providing new methods for lead compound preparation etc.), which could ultimately benefit human health. Previous work by this project’s research team has focused on developing new transition metal catalysts with applications for challenging chemical transformation to reach an efficient synthesis of diverse chemicals for medicinal and biological research. Recently, with the employment of strong oxidants or photoactivation conditions, gold(I) oxidation to gold(III) were realized, despite the intrinsic high oxidation potential. These discoveries further advanced the field of gold catalysis, adding redox chemistry as an alternative path into the catalytic cycle. However, major hurdles in the current gold catalytic system exist that limit its full utility to promote some typical chemical synthesis such as asymmetric transformations in redox chemistry, accessing vinyl-gold intermediate without rapid protodeauration, and integration of gold p- acid reactivity with redox chemistry, etc. The proposed project will address these hurdles by developing new strategies and catalysts and by providing new medicinally important avenues toward structures which are often difficult to access. The project aim will address two fundamental questions in the gold catalysis: 1) Can asymmetric gold redox catalysis be achieved through chiral ligand control with gold(I) as the resting state? and 2) Will the integration of multiple gold catalysis reaction modes (p-acid, vinyl-gold and redox chemistry) be integrated in one cycle to achieve highly efficient transformations with good stereoselectivity. Our research program will focus on the following four specific directions: 1) developing new oxidation conditions to achieve gold oxidation for a broader scope of substrates for gold redox catalysis; 2) applying gold/iron dual catalytic system to access vinyl-gold reactivity for direct C-C and C-X bond construction and macrocyclic compound synthesis; 3) applying chiral N,P ligand to achieve enantioselective alkene di- functionalization to provide the key factors that might influence asymmetric gold redox catalysis; and 4) developing new triazole-based chiral ligands systems to achieve gold(III) asymmetric catalysis for rapid and stereoselective C-C and C-X bond constructions. The research’s expected outcomes will result in new strategies and methods for alternative approaches toward biomedically important molecules and new building blocks as molecular probes or potential therapeutic solution.