Traditional light-induced electron transfer reactions rely on the absorption of a photon by at least one substrate of a reaction mixture, which is thereby converted to an electronically excited state capable of abstracting or donating an electron from or to another substrate. As most organic molecules do not absorb visible light, these reactions are usually UV-driven. Such single-electron transfer (SET) processes primarily result in radical ions, which can undergo unique bond cleaving and bond forming reactions. Thus, despite the use of light (ideally sunlight) as sole energy source, which is consistent with the emerging concept of green chemistry, such SET processes are of great synthetic interest.
As UV-light can sometimes lead to undesired side reactions and is only a minor part of natural sunlight, a lot of effort has been made to develop catalysts capable of triggering SET processes upon excitation by visible light. Such photoredox catalysts are usually polypyridyl-complexes of ruthenium and iridium, organic dyes such as Eosin Y, Rose Bengal and Rhodamine 6G or semiconductors. Upon excitation by light, these catalysts are converted to an electronically excited state which is both, more oxidizing and more reducing, than the ground state to which it is converted by two successive electron transfer reactions. By engaging in these SET-steps, substrates of the reaction mixture can experience previously elusive transformations. After its resurgence in 2008, photoredox catalysis has become one of the most vital research areas within the field of organic chemistry with thousands of publications emphasizing the outstanding opportunities provided by light-induced electron transfer reactions.
Given the general interest of our group in the synthesis and the chemistry of α-aminonitriles, it was particularly pleasing to find that these species can be prepared in a photoredox-catalyzed transformation from the respective tertiary amines. Using the organic dye Rose Bengal as catalyst and atmospheric oxygen as terminal oxidant, a large variety of α-aminonitriles was accessible in high yields. Although Rose Bengal is inexpensive and readily available, it is worth mentioning that the catalyst loading could be reduced to as little as 0.1 ppm, the lowest ever reported for an organic dye-driven photoredox reaction. As highlighted below, this method was successfully applied to the total syntheses of the alkaloid (±)-crispine A as well as the tetraponerines T7 and T8.
As in the example above, our group has generally focused on the use of transition-metal-free photoredox catalysts, as they are less toxic, mostly inexpensive and readily available. Some organic dyes, such as Fukuzumi-acridinium salts, are very strong oxidants while others, such as Rhodamine 6G (upon double excitation), are very strong reductants, but to date, none of them is both. This can however be troublesome if a reaction is to be performed which is very challenging with respect to both, the oxidizing as well as the reducing power of the catalyst. In such cases, phenanthrene can be used. This inexpensive and simple arene exhibits remarkable redox properties when excited by UV-light. Thus, if the substrates of the reaction mixture are known not to undergo UV-driven side reactions, phenanthrene is an ideal catalyst which can be recovered in very high yields.
We have shown its usefulness in the transition-metal-free coupling of carboxylic acids and alcohols (activated as their oxalate half esters) with aromatic nitriles, which was based on work by the groups of Yasuharu Yoshimi and Minoru Hatanaka. A variety of α-amino and α-oxy acids as well as arylacetic acids furnish the coupling products in very high yields and with complete regioselectivity. Even peptides can be coupled in this fashion. The alcohol scope is however limited at ambient temperature.
Aromatic nitriles can also be coupled with benzylic radicals liberated from N-alkylated 1,2,3,4-tetrahydrosioquinolines such as (±)-laudanosine. This finding represents a new reaction mode of this important class of natural products. At the same time, this reaction constitutes the first example of a light-induced C–C-σ-bond metathesis during which two new C–C-bonds are formed at the expense of two unstrained C–C-bonds. Furthermore, we could show that in this case, the merger of the aromatic nitriles´ own light-induced SET-processes with phenanthrene-mediated redox reactions was beneficial for the overall yields compared to an iridium-based protocol under irradiation with visible light simultaneously developed by our group.
We have also focused on light-induced hydrogen atom transfer (HAT) reactions as they open up the possibility to functionalize otherwise inaccessible C–H-bonds. Our primary objective was to use metal-free and inexpensive catalysts such as benzophenone. In this regard, we have recently reported the coupling of 2-chlorobenzazoles with aliphatic carbamates, alcohols and ethers. The reaction is completely deprived of any expensive or toxic reagents and proceeds smoothly under irradiation with weak UV-A light. A variety of coupling products could be prepared in high yields offering novel access to a multitude of substituted benzazoles.
The penetration of light into large flasks is limited hampering photoredox reactions on a big scale. In this case, flow reactors are a good alternative. The increased surface-to-volume ratio leads to a dramatic acceleration of photoreactions while a continuous flow would principally allow for a large throughput of starting materials over time. This is especially desirable if the light source in question is not shining constantly as it is the case for natural sunlight. In this regard we have presented the concept of sunflow, which refers to the use of a microcapillary flow reactor to drive fast and green photoreactions under irradiation with sunlight. We have shown the generality of this concept using three exemplary reactions recently developed by our group.
We have also focused on light-induced hydrogen atom transfer (HAT) reactions as they open up the possibility to functionalize otherwise inaccessible C–H-bonds. Our primary objective was to use metal-free and inexpensive catalysts such as benzophenone. In this regard, we have recently reported the coupling of 2-chlorobenzazoles with aliphatic carbamates, alcohols and ethers. The reaction is completely deprived of any expensive or toxic reagents and proceeds smoothly under irradiation with weak UV-A light. A variety of coupling products could be prepared in high yields offering novel access to a multitude of substituted benzazoles.
The penetration of light into large flasks is limited hampering photoredox reactions on a big scale. In this case, flow reactors are a good alternative. The increased surface-to-volume ratio leads to a dramatic acceleration of photoreactions while a continuous flow would principally allow for a large throughput of starting materials over time. This is especially desirable if the light source in question is not shining constantly as it is the case for natural sunlight. In this regard we have presented the concept of sunflow, which refers to the use of a microcapillary flow reactor to drive fast and green photoreactions under irradiation with sunlight. We have shown the generality of this concept using three exemplary reactions recently developed by our group.
For selected publications on photoredox catalysis please see:
A Highly Active System for the Metal-Free Aerobic Photocyanation of Tertiary Amines with Visible Light: Application to the Synthesis of Tetraponerines and Crispine A
J. C. Orejarena Pacheco, A. Lipp, A. M. Nauth, F. Acke, J.-P. Dietz, T. Opatz
Chem. Eur. J. 2016, 22, 5409-5415.
Transition Metal-free Decarboxylative Photoredox Coupling of Carboxylic Acids and Alcohols with Aromatic Nitriles
B. Lipp, A. M. Nauth, T. Opatz
J. Org. Chem. 2016, 81, 6875-6882.
Light-Induced Alkylation of (Hetero)aromatic Nitriles in a Transition Metal-Free C–C-Bond Metathesis
B. Lipp, A. Lipp, H. Detert, T. Opatz, Org. Lett. 2017, 19, 2054–2057.
Light Induced C–C Coupling of 2-Chlorobenzazoles with Carbamates, Alcohols, and Ethers
A. Lipp, G. Lahm, T. Opatz
J. Org. Chem. 2016, 81, 4890-4897.
Sunflow: Sunlight Drives Fast and Green Photochemical Flow Reactions in Simple Micro Capillary Reactors — Application to Photoredox- and H-Atom Transfer Chemistry
A. M. Nauth, A. Lipp, B. Lipp, T. Opatz, Eur. J. Org. Chem. 2017, 2099–2103.
Link to Video Abstract.
