Burkhard König

The photocatalyzed Meerwein arylation: classic reaction of aryl diazonium salts in a new light.

The use of diazonium salts for aryl radical generation and C-H arylation processes has been known since 1896 when Pschorr first used the reaction for intramolecular cyclizations. Meerwein developed it further in the early 1900s into a general arylation method. However, this reaction could not compete with the transition-metal-mediated formation of C(sp(2))-C(sp(2)) bonds. The replacement of the copper catalyst with iron and titanium compounds improved the situation, but the use of photocatalysis to induce the one-electron reduction and activation of the diazonium salts is even more advantageous. The first photocatalyzed Pschorr cyclization was published in 1984, and just last year a series of papers described applications of photocatalytic Meerwein arylations leading to aryl-alkene coupling products. In this Minireview we summarize the origins of this reaction and its scope and applications.

Metal-Free, Cooperative Asymmetric Organophotoredox Catalysis with Visible Light†

The dawn of old stars: Classic xanthene dyes like eosin Y (gr. eoς=goddess of dawn) and green-light irradiation can replace precious metal complexes for the organocatalytic asymmetric -alkylation of aldehydes rendering the process purely organic.

Metal-Free, Visible-Light-Mediated Direct C–H Arylation of Heteroarenes with Aryl Diazonium Salts

Visible light along with 1 mol % eosin Y catalyzes the direct C-H bond arylation of heteroarenes with aryl diazonium salts by a photoredox process. We have investigated the scope of the reaction for several aryl diazonium salts and heteroarenes. The general and easy procedure provides a transition-metal-free alternative for the formation of aryl-heteroaryl bonds.

Eosin Y catalyzed visible light oxidative C-C and C-P bond formation.

Eosin Y catalyzes efficiently the visible light mediated coupling of sp(3) C-H bonds adjacent to the nitrogen atom in tetrahydroisoquinoline derivatives in the absence of an external oxidant. Nitroalkanes, dialkyl malonates, malononitrile, and dialkyl phophonates were used as pronucleophiles in this metal-free, visible light oxidative coupling reaction.

Low melting mixtures in organic synthesis – an alternative to ionic liquids?

There is a pressing need to replace hazardous and harmful solvents with “green” or “sustainable” media. Natural compounds have recently been used to produce deep eutectic solvents, sugar melts, or ionic liquids. This review presents physicochemical data of these reaction media and highlights recent advances in their use in organic synthesis and biotransformations.

Reduction of aryl halides by consecutive visible light-induced electron transfer processes

Doubling up on optically driven catalysis During photosynthesis, plants absorb light from the Sun four consecutive times before they accumulate enough energy to make oxygen from water. In contrast, when chemists harness light energy to promote reactivity, they tend to rely on single discrete absorption events. Ghosh et al. now show that a particular dye molecule can channel the combined energy from two absorbed photons to the reduction and subsequent coupling reactions of aryl halide molecules. The method expands the reach of photocatalysis to a broader range of compounds, such as chlorides, which are too stable to breach with a single photon. Science, this issue p. 725 A dye molecule channels the energy of two visible photons into aryl substitution reactions. Biological photosynthesis uses the energy of several visible light photons for the challenging oxidation of water, whereas chemical photocatalysis typically involves only single-photon excitation. Perylene bisimide is reduced by visible light photoinduced electron transfer (PET) to its stable and colored radical anion. We report here that subsequent excitation of the radical anion accumulates sufficient energy for the reduction of stable aryl chlorides giving aryl radicals, which were trapped by hydrogen atom donors or used in carbon-carbon bond formation. This consecutive PET (conPET) overcomes the current energetic limitation of visible light photoredox catalysis and allows the photocatalytic conversion of less reactive chemical bonds in organic synthesis.

Conversion of carbohydrates into 5-hydroxymethylfurfural in highly concentrated low melting mixtures

Highly concentrated melt systems consisting of choline chloride (ChCl) and up to 50 wt% of carbohydrates, corresponding to carbohydrate concentrations of 2.9 to 3.1 mol/L, have been used for the conversion of the carbohydrate content into 5-hydroxymethylfurfural (HMF) in the presence of catalysts. Apart from the monosaccharides D-fructose and D-glucose, the disaccharide sucrose and the polyfructan inulin were successfully converted into HMF. The reported conditions with short reaction times at high concentrations may allow for high space-time yields, which may be of interest for the development of efficient continuous processes for the conversion of carbohydrates into HMF. In a preliminary ecological evaluation, the ChCl/D-fructose system is compared to other representative solvents for the synthesis of 5-hydroxymethylfurfural. The melts have an inherent low toxicological impact due to their negligible vapour pressure.

Visible‐Light‐Promoted Stereoselective Alkylation by Combining Heterogeneous Photocatalysis with Organocatalysis

Dream team: Heterogeneous inorganic semiconductors and chiral organocatalysts team up for the stereoselective photocatalytic formation of carbon–carbon bonds. However, the connection between the organic and inorganic catalysts should not be too tight: Covalent immobilization inactivates the system.

Visible Light Mediated Photoredox Catalytic Arylation Reactions

Introducing aryl- and heteroaryl moieties into molecular scaffolds are often key steps in the syntheses of natural products, drugs, or functional materials. A variety of cross-coupling methods have been well established, mainly using transition metal mediated reactions between prefunctionalized substrates and arenes or C-H arylations with functionalization in only one coupling partner. Although highly developed, one drawback of the established sp2-sp2 arylations is the required transition metal catalyst, often in combination with specific ligands and additives. Therefore, photoredox mediated arylation methods have been developed as alternative over the past decade. We begin our survey with visible light photo-Meerwein arylation reactions, which allow C-H arylation of heteroarenes, enones, alkenes, and alkynes with organic dyes, such as eosin Y, as the photocatalyst. A good number of examples from different groups illustrate the broad application of the reaction in synthetic transformations. While initially only photo-Meerwein arylation-elimination processes were reported, the reaction was later extended to photo-Meerwein arylation-addition reactions giving access to the photoinduced three component synthesis of amides and esters from alkenes, aryl diazonium salts, nitriles or formamides, respectively. Other substrates with redox-active leaving groups have been explored in photocatalyzed arylation reactions, such as diaryliodonium and triarylsulfonium salts, and arylsulfonyl chlorides. We discus some examples with their scope and limitations. The scope of arylation reagents for photoredox reactions was extended to aryl halides. The challenge here is the extremely negative reduction potential of aryl halides in the initial electron transfer step compared to, e.g., aryl diazonium or diaryliodonium salts. In order to reach reduction potentials over -2.0 V vs SCE two consecutive photoinduced electron transfer steps were used. The intermediary formed colored radical anion of the organic dye perylenediimide is excited by a second photon allowing the one electron reduction of acceptor substituted aryl chlorides. The radical anion of the aryl halide fragments under the loss of a halide ion and the aryl radical undergoes C-H arylation with biologically important pyrrole derivatives or adds to a double bond. Rhodamine 6G as an organic photocatalyst allows an even higher degree of control of the reaction. The dye is photoreduced in the presence of an amine donor under irradiation with green light (e.g., 530 nm), yielding its radical anion, which is a mild reducing reagent. The hypsochromic shift of the absorption of the rhodamine 6G radical anion toward blue region of the visible light spectrum allows its selective excitation using blue light (e.g., 455 nm). The excited radical anion is highly reducing and able to activate even bromoanisole for C-H arylation reactions, although only in moderate yield. Photoredox catalytic C-H arylation reactions are valuable alternatives to metal catalyzed reactions. They have an excellent functional group tolerance, could potentially avoid metal containing catalysts, and use visible light as a traceless reagent for the activation of arylating reagents.

Visible light photocatalytic synthesis of benzothiophenes.

The photocatalytic reaction of o-methylthio-arenediazonium salts with alkynes yields substituted benzothiophenes regioselectively through a radical annulation process. Green light irradiation of eosin Y initiates the photoredox catalysis. The scope of the reaction was investigated by using various substituted diazonium salts and different alkynes.