| dc.description.abstract | Design of sustainable synthetic methods for oxidation reactions is one of the fundamental
challenges in chemistry, and both aerobic conditions and electrochemistry provide attractive
means to carry out sustainable oxidation reactions. Biological C–H oxidation catalysis routinely
proceeds via highly reactive oxidized metal sites generated from O₂; similar oxidation reactions
are usually carried out in contemporary synthesis using O₂ surrogates such as hypervalent iodine
reagents. These reagents are often used in stoichiometric quantities leading to poor atom economy. In 2018, we reported the development of aerobic hypervalent iodine catalysis predicated on diverting aldehyde autoxidation intermediates towards the oxidation of aryl iodides for sustainable synthesis of both I(III) and I(V) reagents. Many of the transformations for which hypervalent iodine intermediates have been developed, including a-functionalization of carbonyls and metal-free C–H/N–H cross-coupling reactions, were successfully carried out aerobically. We discovered that aryl iodides with weakly-coordinating 2-substituted groups (such as tert-butylsulfonyl) yielded the corresponding I(V) reagents due to disproportionation of initially formed I(III) derivatives under the autoxidation reaction conditions and leveraged that for aerobic alcohol oxidation chemistry. Under autoxidation conditions, 1,2-diols afforded alcohol oxidation accompanied with C–C bond cleavage — characteristic of Dess-Martin Periodinane (DMP). Thus, this discovery serves as the first example of aerobic oxidation catalysis involving DMP analogue.
Detailed mechanistic studies of the aerobic oxidation chemistry led to identification of facile one-electron oxidation and the development of electrocatalytic hypervalent iodine chemistry. We demonstrated the viability of hypervalent iodine electrocatalysis in the context of both intra- and intermolecular C–H amination reactions, forming carbazole and aromatic hydrazine derivatives, respectively via iodanyl radical catalysis. To expand the scope of amination reactions, we have developed new class of N-aminopyridinium reagents through benzyl C–H aminopyridylation, and utilized in the synthesis of tetrahydroisoquinolines and a-aminated carbonyl compounds.
Finally, a new family of aminating reagents, based on N-aminopyridinium scaffolds, were developed in response to the oxidative lability of many amine precursors under the strongly oxidizing conditions required for iodine-centered oxidation.
Given the breadth of chemistry available for hypervalent iodine compounds, demonstration of strategies to facilitate the aerobic and electrochemical generation of hypervalent iodine species
promises to significantly impact the sustainable use of hypervalent iodine intermediates in
synthesis. | |
