Building Catalytic Reactions One Electron at a Time

ConspectusClassical education in organic chemistry and catalysis, not the least my own, has centered on two-electron transformations, from nucleophilic attack to oxidative addition. The focus on two-electron chemistry is well-founded, as this brand of chemistry has enabled incredible feats of synthesis, from the development of life-saving pharmaceuticals to the production of ubiquitous commodity chemicals. With that said, this approach is in many ways complementary to the approach of nature, where enzymes frequently make use of single-electron "radical" steps to achieve challenging reactions with exceptional selectivity, including light detection and C-H hydroxylation. While the power of radical elementary steps is undeniable, the fundamental understanding of─and ability to apply─these in catalysis remains underdeveloped, constraining the palette with which chemists can make new reactions.Motivation to remedy this traditional underemphasis on radical catalysis has been intensified by the runaway success of outer-sphere photoredox catalysis, not only confirming the versatility of radicals in anthropogenic catalysis but also teaching the value of robust and well-understood catalytic cycles for reaction design. Indeed, I would argue the success of outer-sphere photoredox catalysis has been fueled by strong fundamental understanding of its underlying radical elementary steps, with consideration of single-electron transfer (SET) energetics allowing new reactions to be designed