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.






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Figure 1


Ruthenium polypyridyl complexes: versatile visible light photocatalysts.

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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

(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.

The highly efficient and diastereoselective synthesis of E dienes has been accomplished through radical cyclization of bromoallyl hydrazones. This methodology has been further extended to generate these products through a one-pot condensation/radical cyclization/cycloreversion cascade from simple aldehyde starting materials in high yields (>75 %) and high diastereoselectivities (>95:5). Mechanistic investigations suggest that the cascade reaction proceeds through a cyclic diazene intermediate prior to the cycloreversion.

Single-Electron/Pericyclic Cascade for the Synthesis of Dienes.

Facile synthesis of sulfonyl fluorides from sulfonic acids

Tetrahydrocannabinol
acid (THCA) and cannabidiol acid (CBDA), the two crucial organic components in
cannabis and hemp, decarboxylate at different rates to their more active
neutral forms. Theoretical calculations are used herein to analyze how the
remote annulated ring or pendant substituent influences the rate determining steps
of the decarboxylation processes. The uncatalyzed keto-enol tautomerization
that precedes decarboxylation is found to be extremely slow in both cases
albeit with a ten-fold preference for CBDA. A single molecule of methanol
dramatically enhances the reaction rates by allowing for tautomerization
through a more favorable six-membered ring transition state. Methanol-catalyzed
tautomerization is found to be faster in THCA than in CBDA. This difference
results from both the larger dipole moment of the THCA scaffold as well as its
greater rigidity relative to CBDA. The greater dipole moment leads to a
somewhat better binding of methanol. The lower entropic penalty in THCA towards
tautomerization leads to faster decarboxylation.

Why Is THCA Decarboxylation Faster than CBDA? an in Silico Perspective

Radical cascades reactions have been extensively used in organic synthesis for the rapid construction of molecular complexity, and have shown to be particularly effective in the assembly of polycyclic cores. Through careful substrate design, their application has extended from carbocyclic to heterocyclic frameworks. In this chapter, we describe radical cascade processes that generate oxygen- and nitrogen-containing polycyclic structures in the context of total synthesis. The radical cascades either directly form the heterocycle or incorporate/modify preexisting heterocycles to further elaborate the target’s core. Total syntheses where the radical cascade had no impact on the formation or modification of the heterocyclic moiety are not included in this review.

Glenn M. Sammis

Papers

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

Single-Electron/Pericyclic Cascade for the Synthesis of Dienes.

Facile synthesis of sulfonyl fluorides from sulfonic acids

Why Is THCA Decarboxylation Faster than CBDA? an in Silico Perspective

Radical Cascades in the Total Synthesis of Complex Naturally Occurring Heterocycles