HIGH-THROUGHPUT ELECTROSYNTHESIS AND THE GENERALITY-ORIENTED DEVELOPMENT OF OXOAMMONIUM CATALYSIS
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Redox transformations are of fundamental importance to organic chemistry and are the basis for the conversion of hydrocarbon feedstocks to value added (oxidized) densely functionalized pharmaceuticals, agrochemicals, or materials. This dissertation covers two distinct modes or redox chemistry: (1) Chapters 1–3 discuss the development of technological solutions to enable high-throughput electrosynthesis. (2) Chapters 4–7 discuss the development of oxoammonium catalysis for the oxidative desymmetrization diols and the racemic and asymmetric C–H oxidation of N-protected amines.(1) In the recent decade electrochemistry has emerged as an enabling green technology in organic synthesis. Concurrently, high-throughput experimentation (HTE) has seen broad applications in many areas of organic chemistry, accelerating academic and industrial chemical research in reaction development and drug discovery. However, application of HTE in electrosynthesis has been limited by a dearth of suitable standardized reactors. Herein, we report the development of HTe-Chem: a standardized well plate-based reactor for 24 well parallel electrosynthesis, capable of supporting virtually any electrosynthetic reaction condition (chapter 2). We also report the development of SPECS, microscale electronic devices that enable wireless electrosynthesis with up to 384 parallel reactions, using light as an energy source (chapter 3). (2) The hydroxylamine/aminoxyl radical/oxoammonium cation redox couples are privileged organocatalysts for redox chemistry due to their stability in all three oxidation states, most notably leading to their application as ppm level catalysts for alcohol oxidation. Despite this, asymmetric variants remain rare. Herein, we report a novel aminoxyl-peptide platform for the desymmetrization of meso-diols (chapter 5). We also developed a broadly applicable oxoammonium catalyzed C–H oxidation of N-protected amines via a unique hydride abstraction mechanism (chapter 6). By combining both methods, we achieved the oxidative desymmetrization of N-protected heterocycles (chapter 7 and chapter 8). Notably, three works apply a generality-oriented optimization, employing screening of every catalyst against every substrate as an enabling strategy to achieve a broad substrate scope.