Photochemistry holds immense promise as a tool for chemical synthesis. When molecules absorb light, they can access electronically excited states ~40–90 kcal/mol higher in energy than their closed-shell, ground-state configurations. The high-energy reactive intermediates characteristic of photochemical activation can engage in remarkable transformations that would be difficult to accomplish in any other way. The ability to control the outcomes of their reactions, however, has been a long-standing challenge with few comprehensive solutions. The central goal of research in the Yoon laboratory is to develop strategies for the controlled photochemical synthesis of complex molecules.
Research Theme 1: Enantioselective catalysis of photochemical reactions
Research in our laboratory aims to achieve comprehensive control over the chemoselectivity, regioselectivity, and stereoselectivity of photochemical reactions. While we are interested in all of these aspects, our primary focus lies on achieving stereocontrol. Prior to 2005, when we began to investigate this topic, only a handful of highly enantioselective catalytic photoreactions were known, and few of these proof-of-principle studies could be considered synthetically practical. Over the past two decades, we have contributed several innovative, generalizable strategies for highly enantioselective catalytic photochemistry.
New photocatalyst structures. We have designed novel chiral asymmetric photocatalysts. These complexes are based upon Ir-centered chromophores with exceptional photocatalytic efficiency. We introduce hydrogen-bonding domains that bind to Lewis basic organic substrates and position them in a well-defined orientation relative to the metal stereocenter. This class of catalysts have proven to be among the most efficient asymmetric photocatalysts reported to date: highly enantioselective photocycloadditions occur with loadings as low as 0.2 mol %. Current efforts in our laboratory are aimed towards applying this design towards other classes of important photoreactions.
Dual catalysis of asymmetric photoreactions. Arguably our most influential strategy for asymmetric photochemistry has involved the use of Ru or Ir photocatalysts in tandem with chiral Lewis or Brønsted acidic co-catalysts. These dual catalytic systems have been enabled by the discovery that acid coordination can dramatically accelerate photoinduced electron- and energy-transfer processes. Notably, these reactions utilize the same families of privileged chiral Lewis and Brønsted acid catalyst structures that have proven to be so general in ground-state asymmetric reactions, and whose stereocontrol features are consequently well understood.
Research Theme 2: Novel strategies for photochemically enabled synthesis
Our understanding of photochemical reaction mechanisms has developed rapidly over the past two decades. We have recently begun to apply these insights to develop projects in which synthetic utility is a primary design criterion.
• Oxidative photochemical transformations. A surprising observation from the recent surge of interest in photoredox catalysis has been that net-oxidative photochemical reactions are surprisingly difficult to develop compared to net-reductive or redox-neutral photoreactions. We have argued that this discrepancy could be attributed in part to the characteristic odd-electron mechanisms of photoredox reactions. The conventional terminal oxidants most common in ground-state catalytic oxidations (e.g., molecular oxygen, peroxides) are incompatible with these mechanisms because they undergo one-electron reduction to generate highly reactive heteroatom-centered radical species (e.g., superoxide, oxyl radicals). Many terrestrially abundant first-row transition metals, in contrast, more readily accommodate one-electron oxidation-state changes. We have shown that inexpensive base-metal oxidants are an attractive alternative solution and provide a versatile means to design useful new net-oxidative photoreactions with synthetic capabilities that complement the state of the art.
Decarboxylative functionalization reactions. Carboxylic acids are among the most common functional groups present in commercial libraries of compounds for drug discovery. Versatile methods for decarboxylative functionalization of these diverse building block sets, consequently, are of substantial contemporary interest in the pharmaceutical industry. Modern photocatalytic strategies can be leveraged towards innovative new transformations of these structurally diverse feedstocks. For example, we have recently reported a method for the preparation of unsymmetrical ketones by chemoselective cross-coupling of two different carboxylic acid feedstocks. Our method takes advantage of the complementary selectivity of the catalytic cycles in metallaphotoredox reactions: the generation of Ni(II) acyl intermediates is sensitive to steric bulk, while the selectivity of photoredox decarboxylation is governed by electronic considerations.
We have also become interested in the native photochemistry of metal-carboxylate coordination complexes. The use of Cu(II) and Fe(III) salts both as light-absorbing species and as terminal oxidants has enabled us to design highly modular methods to couple carboxylic acid feedstocks with diverse nucleophilic reaction partners to forge carbon–oxygen, carbon–nitrogen, and carbon–carbon bonds.
Research Theme 3: Investigation of photochemical reaction mechanisms.
Our approach to research is premised on the view that deeply interrogating mechanism can have greater impact than new reaction methods alone. We have contributed several insights into the mechanisms of photocatalytic reactions that have significantly influenced the development of the field. The comprehensive elucidation of photochemical reaction mechanisms is challenging, and we have found it beneficial to engage collaborators with complementary expertise in time-resolved spectroscopy and in computation to fully rationalize the outcomes of reactions developed in our laboratory.
The integration of multiple analytical techniques is a consistent theme throughout our research. We take great pride in the scholarly contributions that have emerged from our work, which provide fundamental insights into the principles that underpin controlled photocatalytic synthesis.