“Activation of arene-heteroatom bonds by photoredox catalysis with visible light” Dissertation zur Erlangung des Doktorgrades der Naturwissenschaften Dr. rer. nat. an der Fakultät für Chemie und Pharmazie der Universität Regensburg vorgelegt von Michal Májek aus Bratislava (Slowakische Republik) Regensburg 2015 The experimental part of this work was carried out between September 2012 and September 2015 at the University of Regensburg, Institute of Organic Chemistry under the supervision of Prof. Dr. Axel Jacobi von Wangelin. The thesis was submitted on: 6.11.2015 Date of the defense: 10.12.2015 Board of examiners: Prof. Dr. Olga García Mancheño (chairman) Prof. Dr. Axel Jacobi von Wangelin (1st referee) Prof. Dr. Burkhard König (2nd referee) Prof. Dr. Frank-Michael Matysik (examiner) Hey, now, baby, I’m beginning to see the light Wine in the morning and some breakfast at night Well, I’m beginning to see the light… Velvet Underground: Beginning to see the light (1968) Table of Contents: 1: Introduction 1.1 Chemistry and light 11 1.2 Chemical photocatalysis: Introduction 16 1.2.1 Chemical photocatalysis: Sensitizers 17 1.2.2 Chemical photocatalysis: Redox catalysis 19 1.2.3 Chemical photocatalysis: Scope of photoredox catalysis 25 1.3 Conclusions and outlook 32 1.4 Thesis scope 32 1.5 References 34 2: Organocatalytic visible light mediated synthesis of aryl sulfides 2.1 Introduction 41 2.2 Results and discussion 43 2.3 Conclusion 46 2.4 Experimental part 46 2.5 References 59 3: On the mechanism of photocatalytic reactions with eosin Y 3.1 Introduction 63 3.2 Results and discussion 66 3.3 Conclusion 76 3.4 Experimental and computational part 76 3.5 References 87 4: Visible photo-redox catalysis enables metal-free carbonylations 4.1 Introduction 91 4.2 Results and discussion 94 4.3 Conclusion 104 4.4 Experimental and computational part 104 4.5 References 124 5: Visible light-driven hydro/deutero defunctionalization of anilines 5.1 Introduction 129 5.2 Results and discussion 131 5.3 Conclusion 139 5.4 Experimental and computational part 139 5.5 References 147 6: Photocatalytic synthesis of pyrazoles 6.1 Introduction 151 6.2 Results and discussion 154 6.3 Conclusion 160 6.4 Experimental part 160 6.5 References 170 7: Visible-to-UV photon upconversion for photoredox catalysis 7.1 Introduction 173 7.2 Results and discussion 177 7.3 Conclusion 183 7.4 Computational part 184 7.5 References 188 8: Appendix 8.1 List of abbreviations 193 8.2 Summary 195 8.3 Zusammenfassung 196 8.4 Súhrn 197 8.5 Acknowledgements 198 8.6 CV and list of publications 199 8.7 List of figures 203 Chapter 1: Introduction Introduction 1.1: Chemistry and light Light-induced reactions are as old as is the Earth itself, preceding life by hundreds of millions of years. As a matter of fact, the most probable source of the simplest organic molecules such as formaldehyde, which became the building for more complex molecules, starting with carbohydrates, were photochemical processes. Spectrum of the young Sun contained much more of the energetic UV light, and there was no ozone layer to protect the surface of the Earth, therefore photochemistry started immediately as the accretion processes finished and the stardust settled on the surface of the Earth.1 Later on, living autotrophic organisms emerged on Earth, harnessing the light for the first time as an energy source for the living matter. Chlorophyll became integral for this process, as the first photocatalyst to use light energy for the separation of charges which is a hallmark of the modern, man-made photocatalysts as well.2 Photosynthesizing organisms switched eventually to water splitting, generating oxygen as the by-product. Hard UV irradiation, which was still present on the surface of the Earth damaged biomacromolecules, endangering the living forms present. Thymine dimer formation by [2+2] cycloaddition was especially dangerous, as it presented a mechanism for long lasting DNA damage.3 DNA repairing mechanisms were developed, but the rate of mutation was so high, that even if the organism survived, proper natural selection could not be operative. Increasing oxygen content in the atmosphere was the key to higher living forms, as it lead to the development of the ozone layer, which photochemicaly filters off the deadly, more energetic, part of UV spectrum.4 Thus photochemistry was involved in all the key steps, which led to the existence of life itself, as well as for making the evolution possible, leading to the higher life forms, including the mankind. Natural phenomena concerning light were intensively studied from the earliest days of science. Theoretical discoveries from optics came, driven by the demand from the more practical fields such as navigation, as well as from the transcendent but popular fields as astrology. While most of the laws of optics were discovered in earlier modern ages, it was not until the discovery of quantum physics, that the photochemical phenomena could be explained, as the wave-particle dichotomy is necessary for such explanations. Even though theory was not sufficient at the time to give any predictions in this field, experimental observations of photochemical phenomena were reported. Bleaching of textiles by sunlight was one of the first technologies developed by ancient Egyptians several thousand years before Christ. Later on, the poor light-fastness of dyes became a problem, as most of the natural dyes faded over time after exposure to sunlight. First scientific report of organic photochemical reaction comes from 1685 (just 20 years after the foundation of first 10 Chapter 1 scientific journal) from England. The report concerns with the isolation of a light-labile dye, which gradually changed hue after the exposure to sunlight (it was an indigo- based dye isolated from a sea mollusk).5 This report is worth mentioning, as it presents for the first time the use of photochemistry for production of an industrial chemical (purple textile dye), as well as the correlation between the intensity of irradiation and the rate of the photochemical reaction: “The Letters, figures, or what else shall be made on the Linnen of Silk will presently appear of a pleasant light green colour, and, if placed in the Sun, will change into following colours… light green… deep green… Sea-green… Watchet-blew… Purplish- red… but the last and most beautifull colour, (after washing in scalding water and sope,) will be much a differing colour from all those mention’d i.e. of a fair bright Crimson, or neer to the Prince’s colour… in the heat of the day, in Summer, the colours will come on so fast, that the sucession of each colour, will scarce be distinguisht. ” (sic.) The developments in inorganic and organic analysis led to the discovery of new photochemical reactions in the 19th century: Döbereiner has discovered the photoreduction of iron(III) by oxalate ligands in 1831, reporting for the first time an example of a photo-induced electron-transfer.6 This reaction became later on the basis of the famous ferri-oxalate actinometer. Only a few years later, the photochemistry of a plant-derived organic compound santonin was discovered. The most important discovery that came from the investigation of the santonin chemistry was the discovery of the wavelength dependence of the photochemical transformations:7 “Das Santonin wird sowohl durch den unterlegten, als durch den blauen und violetten Strahl gefärbt (erster wirkt stärker als die gefärbten Strahlen); der gelbe, grüne und rote bringen nicht die mindeste Veränderung hervor…” (sic.) Towards the end of the 19th century, most important classes of the organic photochemical reactions were discovered: [2+2] cycloadditions,8 double bond cis-trans isomerizations9 and radical halogenations,10 reactions which are still mainly carried out by photochemistry in the laboratories of today. Photochemical discoveries until 1900, were by no means results of targeted research, but more of accidental “byproducts” of other lines of work, which the scientists of 19th century pursued. The change came with Giacomo Luigi Ciamician, a researcher from Bologna, who carried out an extensive screening of organic substrates for photochemistry. He dissolved different organic compounds in variety of solvents, let them expose to the strong Italian sunshine on the roof of his department, and analyzed the products by all the means available to him at the time. This lead to discovery of a large array of new reactions, and the 11 Introduction photochemistry seemed like a viable competitor to the coal tar-based organic chemistry of the early 20th century. Ciamician is probably most famous for his prophetic paper in Science, where he predicted a switchover of the human civilization from the fossil fuels to renewables as soon as 1912:11 “Where vegetation is rich, photochemistry may be left to the plants… On arid lands there will spring up industrial colonies without smoke and without smokestacks; forests of glass tubes will extend over plains and glass buildings will rise everywhere; inside of these will take place the photochemical processes that hitherto have been the guarded secret of the plants, but that will have been mastered by human industry…And if in a distant future the supply of coal becomes completely exhausted, civilization will not be checked for that, for life and civilization will continue as long as sun shines! If our black and nervous civilization, based on coal, shall be followed by a quieter civilization based on the utilization of solar energy, that will not be harmful to progress and to human happiness.” Figure 1. Giacomo Ciamician. 100 years after Ciamician’s article, industry uses vast number of photochemical processes. Photochemistry is on one hand being used in water treatment as an ecologic process, but on the other hand the radical halogenations, once the biggest photochemical process, were used to produce products such as HCH with enormous environmental footprints.