A fundamental aim in the field of catalysis is the development of new modes of small molecule activation. One approach toward the catalytic activation of organic molecules that has received much attention recently is visible light photoredox catalysis. In a general sense, this approach relies on the ability of metal complexes and organic dyes to engage in single-electron-transfer (SET) processes with organic substrates upon photoexcitation with visible light.

Many of the most commonly employed visible light photocatalysts are polypyridyl complexes of ruthenium and iridium, and are typified by the complex tris(2,2′-bipyridine) ruthenium(II), or Ru(bpy)32+ (Figure 1). These complexes absorb light in the visible region of the electromagnetic spectrum to give stable, long-lived photoexcited states.1,2 The lifetime of the excited species is sufficiently long (1100 ns for Ru(bpy)32+) that it may engage in bimolecular electron-transfer reactions in competition with deactivation pathways.3 Although these species are poor single-electron oxidants and reductants in the ground state, excitation of an electron affords excited states that are very potent single-electron-transfer reagents. Importantly, the conversion of these bench stable, benign catalysts to redox-active species upon irradiation with simple household lightbulbs represents a remarkably chemoselective trigger to induce unique and valuable catalytic processes.






Open in a separate window


Figure 1


Ruthenium polypyridyl complexes: versatile visible light photocatalysts.

/pdf/visible-light-photoredox-catalysis-with-transition-metal-5d1oxrsczo.pdf

Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis

In this review, we highlight the use of organic photoredox catalysts in a myriad of synthetic transformations with a range of applications. This overview is arranged by catalyst class where the photophysics and electrochemical characteristics of each is discussed to underscore the differences and advantages to each type of single electron redox agent. We highlight both net reductive and oxidative as well as redox neutral transformations that can be accomplished using purely organic photoredox-active catalysts. An overview of the basic photophysics and electron transfer theory is presented in order to provide a comprehensive guide for employing this class of catalysts in photoredox manifolds.

Organic Photoredox Catalysis

Asymmetric enamine catalysis.

Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo- and transition-metal catalysis. The most challenging transformation remains the formation of the parent C-F bond, primarily as a consequence of the high hydration energy of fluoride, strong metal-fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost-efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.

/pdf/introduction-of-fluorine-and-fluorine-containing-functional-1i8kwiad20.pdf

Introduction of Fluorine and Fluorine-Containing Functional Groups

In recent years, photoredox catalysis has come to the forefront in organic chemistry as a powerful strategy for the activation of small molecules. In a general sense, these approaches rely on the ability of metal complexes and organic dyes to convert visible light into chemical energy by engaging in single-electron transfer with organic substrates, thereby generating reactive intermediates. In this Perspective, we highlight the unique ability of photoredox catalysis to expedite the development of completely new reaction mechanisms, with particular emphasis placed on multicatalytic strategies that enable the construction of challenging carbon–carbon and carbon–heteroatom bonds.

http://pubs.acs.org/doi/pdf/10.1021/acs.joc.6b01449

Photoredox Catalysis in Organic Chemistry

Cooperative heterobimetallic catalysis was used as a design principle to achieve a highly reactive system for the enantioselective conjugate addition of cyanide to α,β-unsaturated imides. A dual-catalyst pathway involving chiral (salen)Al complex 1b and chiral (pybox)Er complex 4b provides measurable improvements in rates and enantioselectivities relative to single-catalyst systems. Mechanistic studies point to a cooperative bimetallic mechanism involving activation of the imide by the Al complex and activation of cyanide by the Er complex.

Cooperative dual catalysis: application to the highly enantioselective conjugate cyanation of unsaturated imides.

The development of new synthetic technologies for the selective fluorination of organic compounds has increased with the escalating importance of fluorine-containing pharmaceuticals. Traditional methods potentially applicable to drug synthesis rely on the use of ionic forms of fluorine (F– or F+). Radical methods, while potentially attractive as a complementary approach, are hindered by a paucity of safe sources of atomic fluorine (F•). A new approach to alkyl fluorination has been developed that utilizes the reagent N-fluorobenzenesulfonimide as a fluorine transfer agent to alkyl radicals. This approach is successful for a broad range of alkyl radicals, including primary, secondary, tertiary, benzylic, and heteroatom-stabilized radicals. Furthermore, calculations reveal that fluorine-containing ionic reagents are likely candidates for further expansion of this approach to polar reaction media. The use of these reagents in alkyl radical fluorination has the potential to enable powerful new transformations...

Fluorine Transfer to Alkyl Radicals

(Salen)Al−Cl complex 1a catalyzes the asymmetric conjugate addition of hydrogen cyanide to α,β-unsaturated imides in high yields and enantioselectivities. The cyanide adducts can readily be converted into a variety of useful chiral building blocks, including α-substituted-β-amino acids and β-substituted-γ-aminobutyric acids. Mechanistic data obtained thus far point to a cooperative bimetallic mechanism for nucleophile and electrophile activation.

Highly Enantioselective, Catalytic Conjugate Addition of Cyanide to α,β-Unsaturated Imides

We have developed the first example of a photoredox catalytic method for the formation of carbon–fluorine (C–F) bonds. The mechanism has been studied using transient absorption spectroscopy and involves a key single-electron transfer from the 3MLCT (triplet metal-to-ligand charge transfer) state of Ru(bpy)32+ to Selectfluor. Not only does this represent a new reaction for photoredox catalysis, but the mild reaction conditions and use of visible light also make it a practical improvement over previously developed UV-mediated decarboxylative fluorinations.

Direct C-F bond formation using photoredox catalysis.

A three-component carboetherification of unactivated alkenes has been developed allowing the rapid building of complexity from simple starting materials. A wide range of α-substituted styrenes underwent smooth reactions with unactivated alkyl nitriles and alcohols to afford γ-alkoxy alkyl nitriles with concomitant generation of a quaternary carbon center. A radical clock experiment provided clear-cut evidence that the reaction proceeds through a tertiary alkyl radical intermediate.

Glenn M. Sammis

Papers

Cooperative dual catalysis: application to the highly enantioselective conjugate cyanation of unsaturated imides.

Fluorine Transfer to Alkyl Radicals

Highly Enantioselective, Catalytic Conjugate Addition of Cyanide to α,β-Unsaturated Imides

Direct C-F bond formation using photoredox catalysis.

Copper‐Catalyzed Intermolecular Carboetherification of Unactivated Alkenes by Alkyl Nitriles and Alcohols