Photoinduced, copper-catalysed direct perfluoroalkylation of heteroarenes.

An efficient and general process is reported for the photoinduced, copper-catalysed direct perfluoroalkylation of C-H bonds in a broad range of heteroarenes with commercially available perfluoroalkyl iodides. This redox neutral process is simply based on the use of [Cu(bcp)DPEPhos]PF6 as the photoredox catalyst in the presence of potassium acetate and smoothly operates at room temperature.

Direct Perfluoroalkylation of C-H Bonds in (Hetero)arenes.

Perfluoroalkylated (hetero)arenes represent an extremely important family of molecules commonly utilized in many areas such as medicinal chemistry, agrochemistry and material sciences. Due to their unique properties, they have attracted significant interest from synthetic chemists and various methods have been developed for their synthesis. Among them, the direct perfluoroalkylation of C(sp2 )-H bonds in (hetero)arenes is one of the most attractive and straightforward ones, provided that it proceeds with high levels of regioselectivity. In this review article, a comprehensive overview of advances in this field is presented, with a special focus on the reaction mechanisms involved in these transformations and their regioselectivity. All methods available have been classified according to the nature of the perfluoroalkyl chain introduced, trifluoromethylation reactions being overviewed in a separate section, and to the nature of the reagents/catalysts required.

A general synthesis of azetidines by copper-catalysed photoinduced anti-Baldwin radical cyclization of ynamides.

A general anti-Baldwin radical 4-exo-dig cyclization from nitrogen-substituted alkynes is reported. Upon reaction with a heteroleptic copper complex in the presence of an amine and under visible light irradiation, a range of ynamides were shown to smoothly cyclize to the corresponding azetidines, useful building blocks in natural product synthesis and medicinal chemistry, with full control of the regioselectivity of the cyclization resulting from a unique and underrated radical 4-exo-dig pathway.

Copper-Catalyzed Direct Perfluoroalkylation of Heteroarenes.

An efficient and broadly applicable process is reported for the copper-catalyzed direct perfluoroalkylation of C-H bonds in heteroarenes with commercially available perfluoroalkyl iodides. This reaction is based on a simple combination of copper(I) iodide and 1,10-phenanthroline enabling the easy reduction of perfluoroalkyl iodides to the corresponding radical species that add to a wide range of heteroarenes including benzofurans, benzothiophenes, (aza)indoles, furans and pyrroles. High levels of regioselectivity were obtained in all cases and the efficiency and robustness of this process was highlighted by the direct perfluoroalkylation of furan-containing peptides.

[(DPEPhos)(bcp)Cu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst.

Our group recently reported the use of [(DPEPhos)(bcp)Cu]PF6 as a general copper-based photoredox catalyst which proved efficient to promote the activation of a broad variety of organic halides, including unactivated ones. These can then participate in various radical transformations such as reduction and cyclization reactions, as well as in the direct arylation of several (hetero)arenes. These transformations provide a straightforward access to a range of small molecules of interest in synthetic chemistry, as well as to biologically active natural products. Altogether, [(DPEPhos)(bcp)Cu]PF6 acts as a convenient photoredox catalyst which appears to be an attractive, cheap and complementary alternative to the state-of-the-art iridium- and ruthenium-based photoredox catalysts. Here, we report a detailed protocol for the synthesis of [(DPEPhos)(bcp)Cu]PF6, as well as NMR and spectroscopic characterizations, and we illustrate its use in synthetic chemistry for the direct arylation of (hetero)arenes and radical cyclization of organic halides. In particular, the direct arylation of N-methylpyrrole with 4-iodobenzonitrile to afford 4-(1-methyl-1H-pyrrol-2-yl)benzonitrile and the radical cyclization of N-benzoyl-N-[(2-iodoquinolin-3-yl)methyl]cyanamide to afford natural product luotonin A are detailed. The scope and limitations of this copper-based photoredox catalyst are also briefly discussed.

A General Copper-based Photoredox Catalyst for Organic Synthesis: Scope, Application in Natural Product Synthesis and Mechanistic Insights.

Organic transformations can broadly be classified into four categories including cationic, anionic, pericyclic and radical reactions. While the last category has been known for decades to provide remarkably efficient synthetic pathways, it has long been hampered by the need for toxic reagents, which considerably limited its impact on chemical synthesis. This situation has come to an end with the introduction of new concepts for the generation of radical species, photoredox catalysis - which simply relies on the use of a catalyst that can be activated upon visible light irradiation - certainly being the most efficient one. The state-of-the-art catalysts mostly rely on the use of ruthenium and iridium complexes and organic dyes, which still considerably limits their broad implementation in chemical processes: alternative readily available catalysts based on inexpensive, environmentally benign base metals are therefore strongly needed. Furthermore, expanding the toolbox of methods based on photoredox catalysis will facilitate the discovery of new light-mediated transformations. This article details the use of a simple copper complex which, upon activation with blue light, can initiate a broad range of radical reactions.