Development of Iodanyl Radical Electrocatalysis

Abstract

Development of sustainable oxidation methods remains a major synthetic challenge and demands strategies that utilize new, more environmentally attractive, catalyst platforms and employ terminal oxidants that produce environmentally benign byproducts. Hypervalent iodine reagents have garnered significant interest in recent years as environmentally benign, and broadly synthetically applicable, alternatives to traditional metal-based oxidants. Several hypervalent iodine-catalyzed methods, based on two-electron I(I)/I(III) redox cycles, have been developed with a variety of terminal oxidants including peroxides, oxygen, and applied potential (i.e., electrochemistry). However, challenges such as (1) the harsh oxidants required for the synthesis of I(III) species, (2) selectively oxidizing aryl iodide catalysts over oxidatively labile substrates, (3) the instability of odd-electron iodine compounds (i.e. iodanyl radicals, I(II)), and (4) carefully choreographing multi-electron bond-breaking and -forming reactions necessary for organic chemistry have plagued hypervalent iodine catalysis in high catalyst loading and limited substrate scope.

In 2020, we reported the development of hypervalent iodine electrocatalysis predicated on intercepting reactive iodanyl radical intermediates towards C–H amination chemistry. Additional catalyst optimization provided an aryl iodide which upon one-electron oxidation results in an isolable and characterizable iodanyl radical. Spectroscopic and computational studies suggest the critical importance of the ortho-iodine functional group in stabilizing the iodanyl radical via a two-centered three-electron (2c-3e) bonding motif. This allowed for catalysis at as low as 0.5 mol% loading and over 100 mV lower applied oxidation potential compared to the original report. The improved catalyst also allowed for additional C–H/E–H coupling reactions.

Detailed mechanistic studies of the electrochemical oxidation chemistry led to the identification of facile one-electron oxidation of aryl iodides to form the active I(II) oxidants. Spectroscopic and computational studies suggest the role of iodanyl radicals, and exogenous base, in a bidirectional proton coupled electron transfer (PCET) mechanism.

The development of strategies to selectively synthesize and control the reactivity of iodanyl radicals provides a platform for hypervalent iodine reactivity that may be complementary to traditionally targeted two-electron cycles. Furthermore, methods based on the successful marriage of electrochemistry with iodanyl radical reactivity promises a sustainable and broadly applicable synthetic method.