Visible-light photocatalysis has evolved over the last decade into a widely used method in organic synthesis. Photocatalytic variants have been reported for many important transformations, such as cross-coupling reactions, α-amino functionalizations, cycloadditions, ATRA reactions, or fluorinations. To help chemists select photocatalytic methods for their synthesis, we compare in this Review classical and photocatalytic procedures for selected classes of reactions and highlight their advantages and limitations. In many cases, the photocatalytic reactions proceed under milder reaction conditions, typically at room temperature, and stoichiometric reagents are replaced by simple oxidants or reductants, such as air, oxygen, or amines. Does visible-light photocatalysis make a difference in organic synthesis? The prospect of shuttling electrons back and forth to substrates and intermediates or to selectively transfer energy through a visible-light-absorbing photocatalyst holds the promise to improve current procedures in radical chemistry and to open up new avenues by accessing reactive species hitherto unknown, especially by merging photocatalysis with organo- or metal catalysis.

Visible-Light Photocatalysis: Does It Make a Difference in Organic Synthesis?

Research and industrial interest in radical C–H activation/radical cross-coupling chemistry has continuously grown over the past few decades. These reactions offer fascinating and unconventional approaches toward connecting molecular fragments with high atom- and step-economy that are often complementary to traditional methods. Success in this area of research was made possible through the development of photocatalysis and first-row transition metal catalysis along with the use of peroxides as radical initiators. This Review provides a brief and concise overview of the current status and latest methodologies using radicals or radical cations as key intermediates produced via radical C–H activation. This Review includes radical addition, radical cascade cyclization, radical/radical cross-coupling, coupling of radicals with M–R groups, and coupling of radical cations with nucleophiles (Nu).

Recent Advances in Radical C-H Activation/Radical Cross-Coupling.

Photokatalyse mit sichtbarem Licht: Welche Bedeutung hat sie für die organische Synthese?

A room-temperature, visible-light-driven N-centered iminyl radical-mediated and redox-neutral C-C single bond cleavage/radical addition cascade reaction of oxime esters and unsaturated systems has been accomplished. The strategy tolerates a wide range of O-acyl oximes and unsaturated systems, such as alkenes, silyl enol ethers, alkynes, and isonitrile, enabling highly selective formation of various chemical bonds. This method thus provides an efficient approach to various diversely substituted cyano-containing alkenes, ketones, carbocycles, and heterocycles.

A Visible-Light-Driven Iminyl Radical-Mediated C-C Single Bond Cleavage/Radical Addition Cascade of Oxime Esters.

An unprecedented and challenging radical-radical cross-coupling of α-aminoalkyl radicals with monofluoroalkenyl radicals derived from gem-difluoroalkenes was achieved. This first example of tandem C(sp(3) )-H and C(sp(2) )-F bond functionalization through visible-light photoredox catalysis offers a facile and flexible access to privileged tetrasubstituted monofluoroalkenes under very mild reaction conditions. The striking features of this redox-neutral method in terms of scope, functional-group tolerance, and regioselectivity are illustrated by the late-stage fluoroalkenylation of complex molecular architectures such as bioactive (+)-diltiazem, rosiglitazone, dihydroartemisinin, oleanic acid, and androsterone derivatives, which represent important new α-amino C-H monofluoroalkenylations.

Monofluoroalkenylation of Dimethylamino Compounds through Radical-Radical Cross-Coupling.

The selective radical/radical cross-coupling of two different organic radicals is a great challenge due to the inherent activity of radicals. In this paper, a copper-catalyzed radical/radical C sp 3 H/P H cross-coupling has been developed. It provides a radical/radical cross-coupling in a selective manner. This work offers a simple way toward β-ketophosphonates by oxidative coupling of aryl ketone o -acetyloximes with phosphine oxides using CuCl as catalyst and PCy 3 as ligand in dioxane under N 2 atmosphere at 130 °C for 5 h, and yields ranging from 47 % to 86 %. The preliminary mechanistic studies by electron paramagnetic resonance (EPR) showed that, 1) the reduction of ketone o -acetyloximes generates iminium radicals, which could isomerize to -sp 3 -carbon radical species; 2) phosphorus radicals were generated from the oxidation of phosphine oxides. Various aryl ketone o -acetyloximes and phosphine oxides were suitable for this transformation.

Copper-Catalyzed Radical/Radical C(sp 3)-H/P-H Cross-Coupling: α-Phosphorylation of Aryl Ketone O-Acetyloximes.

The selective radical/radical cross-coupling of two different organic radicals is a great challenge due to the inherent activity of radicals. In this paper, a copper-catalyzed radical/radical C sp 3H/PH cross-coupling has been developed. It provides a radical/radical cross-coupling in a selective manner. This work offers a simple way toward β-ketophosphonates by oxidative coupling of aryl ketone o-acetyloximes with phosphine oxides using CuCl as catalyst and PCy3 as ligand in dioxane under N2 atmosphere at 130 °C for 5 h, and yields ranging from 47 % to 86 %. The preliminary mechanistic studies by electron paramagnetic resonance (EPR) showed that, 1) the reduction of ketone o-acetyloximes generates iminium radicals, which could isomerize to α-sp3-carbon radical species; 2) phosphorus radicals were generated from the oxidation of phosphine oxides. Various aryl ketone o-acetyloximes and phosphine oxides were suitable for this transformation.

Yongde Cheng

Papers

Copper-Catalyzed Radical/Radical C(sp 3)-H/P-H Cross-Coupling: α-Phosphorylation of Aryl Ketone O-Acetyloximes.

Copper-Catalyzed Radical/Radical C sp 3H/PH Cross-Coupling: α-Phosphorylation of Aryl Ketone O-Acetyloximes†

Copper-Catalyzed Radical/Radical C(sp3)—H/P—H Cross-Coupling: α-Phosphorylation of Aryl Ketone O-Acetyloximes.