The area of catalysis of radical reactions has recently flourished. Various reaction conditions have been discovered and explained in terms of catalytic cycles. These cycles rarely stand alone as unique paths from substrates to products. Instead, most radical reactions have innate chains which form products without any catalyst. How do we know if a species added in "catalytic amounts" is a catalyst, an initiator, or something else? Herein we critically address both catalyst-free and catalytic radical reactions through the lens of radical chemistry. Basic principles of kinetics and thermodynamics are used to address problems of initiation, propagation, and inhibition of radical chains. The catalysis of radical reactions differs from other areas of catalysis. Whereas efficient innate chain reactions are difficult to catalyze because individual steps are fast, both inefficient chain processes and non-chain processes afford diverse opportunities for catalysis, as illustrated with selected examples.

Catalysis of Radical Reactions: A Radical Chemistry Perspective.

Herein, the development of visible light-mediated atom transfer radical addition (ATRA) of haloalkanes onto alkenes and alkynes using the reductive and oxidative quenching of [Ir{dF(CF3)ppy}2(dtbbpy)]PF6 and [Ru(bpy)3]Cl2 is presented. Initial investigations indicated that the oxidative quenching of photocatalysts could effectively be utilized for ATRA, and since that report, the protocol has been expanded by broadening the scope of the reaction in terms of the photocatalysts, substrates, and solvents. In addition, further modifications of the reaction conditions allowed for the efficient ATRA of perfluoroalkyl iodides onto alkenes and alkynes utilizing the reductive quenching cycle of [Ru(bpy)3]Cl2 with sodium ascorbate as the sacrificial electron donor. These results signify the complementary nature of the oxidative and reductive quenching pathways of photocatalysts and the ability to predictably direct reaction outcome through modification of the reaction conditions.

Visible light-mediated atom transfer radical addition via oxidative and reductive quenching of photocatalysts.

Katalyse von Radikalreaktionen: Konzepte aus Sicht der Radikalchemie

Olefin difunctionalizations via visible light photocatalysis

This article reports on recent advances in the area of catalyst regeneration in copper mediated atom transfer radical addition (ATRA) and cyclization (ATRC) reactions using free‐radical diazo initiators as reducing agents. The role of reducing agent in both processes is to continuously regenerate the activator (copper(I) complex) from the deactivator (copper(II) complex). As a result, single addition adducts in ATRA and ATRC reactions can be synthesized using very low concentrations of copper catalysts (5–100 pm). Previously, efficient catalysis for both processes required as much as several thousands ppm of copper. It is envisioned that the recent developments in this area could have important industrial implications on the synthesis of small organic molecules, natural products and pharmaceutical drugs.

Copper Catalyzed Atom Transfer Radical Addition (ATRA) and Cyclization (ATRC) Reactions in the Presence of Reducing Agents

The synthesis, characterization and exceptional activity of Cu I (TPMA)Br [TPMA = tris(2-pyridylmethyl)amine] and [Cu II (TPMA)Br][Br] complexes in ATRA reactions of polybrominated compounds to alkenes in the presence of reducing agent (AIBN) was reported. [Cu II (TPMA)Br][Br], in conjunction with AIBN, effectively catalyzed ATRA reactions of CBr 4 and CHBr 3 to alkenes with concentrations between 5 and 100 ppm, which is the lowest number achieved in copper-mediated ATRA. The molecular structure of Cu I (TPMA)Br indicated that the complex was pseudo-pentacoordinate in the solid state due to the coordination of TPMA [Cu I -N: 2.1024(15), 2.0753(15), 2.0709(15) and 2.4397(14) A] and bromide anion to the copper(I) center [CU I -Br 2.5088(3) A]. Variable temperature 1 H NMR and cyclic voltammetry studies confirmed the equilibrium between Cu I (TPMA)Br and [Cu I -(TPMA)(CH 3 CN)][Br], indicating some degree of halide anion dissociation in solution. The coordination of the bromide anion to the [Cu I (TPMA)] + cation resulted in a formation of much more reducing Cu I (TPMA)Br complex (E 1/2 = -720 mV vs. Fc/Fc + ) than the corresponding ClO 4 - (E 1/2 = -422 mV vs. Fc/Fc + ) and PF 6 - (E 1/2 = -421 mV vs. Fc/Fc + ) analogues. In [Cu II (TPMA)Br][Br], the Cu II atom was coordinated by four nitrogen atoms [Cu II -N eq 2.073(2) A and Cu II -N ax 2.040(3) A] from TPMA ligand and a bromine atom [Cu II -Br 2.3836(6) A]. The overall geometry of the complex was distorted trigonal bipyramidal. Cu I (TPMA)Br and [Cu II (TPMA)-Br][Br] complexes showed similar structural features from the point of view of TPMA coordination. The only more pronounced difference in the TPMA coordination to the copper center was observed in the shortening of Cu-N ax bond length by approximately 0.400 A on going from Cu I (TPMA)Br to [Cu II (TPMA)Br][Br].

Sean T. Garrity

Papers

Highly Efficient Copper-Mediated Atom-Transfer Radical Addition (ATRA) in the Presence of Reducing Agent