In this thesis, we will try to address the issue of increasing the dielectric constant, by util-izing high electronegativity of fluorine atoms.

In Chapter 2 we give a brief overview of existing fluorination methods and attempt to elucidate the general pathways of introducing the fluorine moieties into organic scaf-folds. We grouped the most common literature methods into three categories: direct fluorination (which is in turn sub-categorized by reaction mechanism), polyfuoroal-kylation (introduction of polyfluoroalkyl group directly into organic substrate, also sub-categorized by reaction mechanism), and synthon approach (formation of fluorine-con-taining compounds from simpler reagents, that readily contain desired fluorine moiet-ies).

In Chapter 3 we describe the synthesis of a discrete hominal bis(difluoromethyl) unit. We found out that, in the case of short chains, the consecutive deoxofluorination of sequentially introduced keto groups is inefficient, as it requires harsh conditions and decreasing yields at each step. To solve this problem, we combined the selective desul-furative fluorination of dithiolanes with pyridinium fluoride and the deoxofluorination of keto groups with morpholinosulfur trifluoride. This strategy is highly reproducible and scalable, allowing the synthesis of the hominal bis(gem-CF2) fragment as a shelf-stable tosylate, in order to introduce this unit on a variety of synthons and monomers.

In Chapter 4 we explore the effect of ether activation on deoxofluorination reactions.

To achieve this, we synthesized a small library of precursor ketones. We varied substitu-ents in direct proximity to the keto group and tested deoxofluorination reaction using several reaction conditions. This highlighted the activating effect of ether group located in 1,3 relation to ketone along the aliphatic chain, which allowed successful transforma-tion into the CF2group, whereas it was problematic, if even possible, for other substitu-ents. We also propose a plausible mechanism, which showcases the possible contribu-tion of the ether group in directing deoxofluorinating agents. We performed calculacontribu-tions

1

of intermediate and transition state structures and calculated their energetic profiles.

These calculations showed a clear effect of ether substituent in lowering the energy bar-rier of one of the transition states.

In Chapter 5 we attempt polymerization of monomers with fluorine-containing or TEG side-chains, in order to draw comparison with model P3HT polymer (used as a benchmark donor material in BHJ OPV devices). We encountered difficulties introdu-cing hominal bis(gem-CF2) fragment, so using the ether-activation approach, we syn-thesized 3-(1,1-difluoro-2-methoxyethyl)thiophene, and used it as a starting point of our tests. While electropolymerization technique succeeded, more conventional synthetic polymerization approaches failed. We postulate that attaching a CF2moiety next to the thiophene core leads to the withdrawal of electron density, which undermines oxidative addition steps of synthetic polymerization. Possible solutions, such as placement of CF2 group further from the core, use of dimer or copolymers of fluorinated monomers are proposed.

B

IBLIOGRAPHY

[1] T. L. Floyd. Electronic Devices. What’s New in Trades & Technology. Pearson, 2017.

ISBN 9780134414447.

[2] V. E. Lashkaryov. Investigations of a barrier layer by the thermoprobe method.

Izvestiia Akademii Nauk SSSR Seriya Fizicheskaya, 5:442–446, 1941.

[3] D. M. Chapin, C. S. Fuller, and G. L. Pearson. A new silicon p-n junction photocell for converting solar radiation into electrical power. Journal of Applied Physics, 25 (5):676–677, 1954.

[4] M. A. Green. Solar cells: operating principles, technology, and system applications.

Prentice-Hall, Inc.,Englewood Cliffs, NJ, 1982.

[5] A. Louwen, W. van Sark, R. Schropp, and A. Faaij. A cost roadmap for silicon hetero-junction solar cells. Solar Energy Materials and Solar Cells, 147:295 – 314, 2016.

[6] R. M. Swanson. Approaching the 29% limit efficiency of silicon solar cells. In Confer-ence Record of the Thirty-first IEEE Photovoltaic Specialists ConferConfer-ence, 2005., pages 889–894, 2005.

[7] W. Shockley and H. J. Queisser. Detailed balance limit of efficiency of p-n junction solar cells. Journal of Applied Physics, 32(3):510–519, 1961.

[8] P. Würfel and U. Würfel. Physics of Solar Cells: From Basic Principles to Advanced Concepts. Wiley, 2016. ISBN 9783527413126.

[9] N.-G. Park. Perovskite solar cells: an emerging photovoltaic technology. Materials Today, 18(2):65 – 72, 2015.

[10] H. Letheby. On the production of a blue substance by the electrolysis of sulphate of aniline. Journal of the Chemical Society, 15:161–163, 1862.

1

[11] N. Hall. Twenty-five years of conducting polymers. Chemical Communications, pages 1–4, 2003.

[12] H. Spanggaard and F. C. Krebs. A brief history of the development of organic and polymeric photovoltaics. Solar Energy Materials and Solar Cells, 83(2):125 – 146, 2004.

[13] F. Ebisawa, T. Kurokawa, and S. Nara. Electrical properties of poly-acetylene/polysiloxane interface. Journal of Applied Physics, 54(6):3255–3259, 1983.

[14] C. W. Tang and S. A. Van Slyke. Organic electroluminescent diodes. Applied Physics Letters, 51(12):913–915, 1987.

[15] Y.-W. Su, S.-C. Lan, and K.-H. Wei. Organic photovoltaics. Materials Today, 15(12):

554 – 562, 2012.

[16] S. Günes, H. Neugebauer, and N. S. Sariciftci. Conjugated polymer-based organic solar cells. Chemical Reviews, 107(4):1324–1338, 2007.

[17] C. W. Tang. Two-layer organic photovoltaic cell. Applied Physics Letters, 48(2):183–

185, 1986.

[18] C. E. Small, S. Chen, J. Subbiah, C. M. Amb, S.-W. Tsang, T.-H. Lai, J. R. Reynolds, and F. So. High-efficiency inverted dithienogermole-thienopyrrolodione-based poly-mer solar cells. Nature Photonics, 6:115 EP, 2011.

[19] W. Li, A. Furlan, K. H. Hendriks, M. M. Wienk, and R. A. J. Janssen. Efficient tandem and triple-junction polymer solar cells. Journal of the American Chemical Society, 135(15):5529–5532, 2013.

[20] T. Hahn, S. Tscheuschner, F.-J. Kahle, M. Reichenberger, S. Athanasopoulos, C. Saller, G. C. Bazan, T.-Q. Nguyen, P. Strohriegl, H. Bässler, and A. Köhler.

Monomolecular and bimolecular recombination of electron–hole pairs at the inter-face of a bilayer organic solar cell. Advanced Functional Materials, 27(1):1604906, 2017.

[21] C. Guillén and J. Herrero. High-Performance Electrodes for Organic Photovoltaics, pages 399–423. Wiley-VCH Verlag GmbH & Co. KGaA, 2009. ISBN 9783527623198.

[22] O. V. Mikhnenko, P. W. M. Blom, and T.-Q. Nguyen. Exciton diffusion in organic semiconductors. Energy & Environmental Science, 8:1867–1888, 2015.

[23] M. Hiramoto, H. Fujiwara, and M. Yokoyama. Three-layered organic solar cell with a photoactive interlayer of codeposited pigments. Applied Physics Letters, 58(10):

1062–1064, 1991.

[24] G. Yu, J. Gao, J. C. Hummelen, F. Wudl, and A. J. Heeger. Polymer photovoltaic cells: Enhanced efficiencies via a network of internal donor-acceptor heterojunc-tions. Science, 270(5243):1789–1791, 1995.

1

[25] J. J. M. Halls, C. A. Walsh, N. C. Greenham, E. A. Marseglia, R. H. Friend, S. C. Moratti, and A. B. Holmes. Efficient photodiodes from interpenetrating polymer networks.

Nature, 376:498 EP, 1995.

[26] A. J. Heeger. 25th anniversary article: Bulk heterojunction solar cells: Understand-ing the mechanism of operation. Advanced Materials, 26(1):10–28, 2014.

[27] A. J. Moulé, J. B. Bonekamp, and K. Meerholz. The effect of active layer thickness and composition on the performance of bulk-heterojunction solar cells. Journal of Applied Physics, 100(9):094503, 2006.

[28] M. A. Brady, G. M. Su, and M. L. Chabinyc. Recent progress in the morphology of bulk heterojunction photovoltaics. Soft Matter, 7:11065–11077, 2011.

[29] G. F. Burkhard, E. T. Hoke, S. R. Scully, and M. D. McGehee. Incomplete exciton harvesting from fullerenes in bulk heterojunction solar cells. Nano Letters, 9(12):

4037–4041, 2009.

[30] S. H. Park, A. Roy, S. Beaupré, S. Cho, N. Coates, J. S. Moon, D. Moses, M. Leclerc, K. Lee, and A. J. Heeger. Bulk heterojunction solar cells with internal quantum effi-ciency approaching 100%. Nature Photonics, 3:297–302, 2009.

[31] J. J. van Franeker, M. Turbiez, W. Li, M. M. Wienk, and R. A. J. Janssen. A real-time study of the benefits of co-solvents in polymer solar cell processing. Nature Com-munications, 6:6229, 2015.

[32] R. C. Chiechi, R. W. A. Havenith, J. C. Hummelen, L. J. A. Koster, and M. A. Loi.

Modern plastic solar cells: Materials, mechanisms and modeling. Materials Today, 16(7-8):281–289, 2013.

[33] J. D. Servaites, M. A. Ratner, and T. J. Marks. Practical efficiency limits in organic photovoltaic cells: Functional dependence of fill factor and external quantum effi-ciency. Applied Physics Letters, 95(16):163302, 2009.

[34] J. Brebels, J. V. Manca, L. Lutsen, D. Vanderzande, and W. Maes. High dielectric con-stant conjugated materials for organic photovoltaics. Journal of Materials Chem-istry A, 5:24037–24050, 2017.

[35] M. C. Scharber, D. Mühlbacher, M. Koppe, P. Denk, C. Waldauf, A. J. Heeger, and C. J. Brabec. Design rules for donors in bulk-heterojunction solar cells—towards 10% energy-conversion efficiency. Advanced Materials, 18(6):789–794, 2006.

[36] R. C. Chiechi and J. C. Hummelen. Polymer electronics, quo vadis? ACS Macro Letters, 1(10):1180–1183, 2012.

[37] Y. Tamai, H. Ohkita, H. Benten, and S. Ito. Exciton diffusion in conjugated polymers:

From fundamental understanding to improvement in photovoltaic conversion effi-ciency. The Journal of Physical Chemistry Letters, 6(17):3417–3428, 2015.

1

[38] M. A. Loi, S. Toffanin, M. Muccini, M. Forster, U. Scherf, and M. Scharber.

Charge transfer excitons in bulk heterojunctions of a polyfluorene copolymer and a fullerene derivative. Advanced Functional Materials, 17(13):2111–2116, 2007.

[39] P. A. Lane, X. Wei, and Z. V. Vardeny. Spin and spectral signatures of polaron pairs in π-conjugated polymers. Physical Review B, 56:4626–4637, 1997.

[40] L. Jan Anton Koster, Sean E. Shaheen, and Jan C. Hummelen. Pathways to a new efficiency regime for organic solar cells. Advanced Energy Materials, 2(10):1246–

1253, 2012.

[41] U. Würfel, A. Cuevas, and P. Würfel. Charge carrier separation in solar cells. IEEE Journal of Photovoltaics, 5(1):461–469, 2015.

[42] NREL. Best research-cell efficiency chart. URL https://www.nrel.gov/pv/

cell-efficiency.html.

[43] L. Kegelmann, C. M. Wolff, C. Awino, F. Lang, E. L. Unger, L. Korte, T. Dittrich, D. Ne-her, B. Rech, and S. Albrecht. It takes two to tango—double-layer selective contacts in perovskite solar cells for improved device performance and reduced hysteresis.

ACS Applied Materials & Interfaces, 9(20):17245–17255, 2017.

[44] I. Gelmetti, L. Cabau, N. F. Montcada, and E. Palomares. Selective organic contacts for methyl ammonium lead iodide (MAPI) perovskite solar cells: Influence of layer thickness on carriers extraction and carriers lifetime. ACS Applied Materials & In-terfaces, 9(26):21599–21605, 2017.

[45] Y.-H. Chiang, C.-K. Shih, A.-S. Sie, M.-H. Li, C.-C. Peng, P.-S. Shen, Y.-P. Wang, T.-F. Guo, and P. Chen. Highly stable perovskite solar cells with all-inorganic select-ive contacts from microwave-synthesized oxide nanoparticles. Journal of Materials Chemistry A, 5:25485–25493, 2017.

[46] J. Sanchez-Diaz, R. S. Sánchez, S. Masi, M. Kreˆcmarová, A. O. Alvarez, E. M. Barea, J. Rodriguez-Romero, V. S. Chirvony, J. F. Sánchez-Royo, J. P. Martinez-Pastor, and I. Mora-Seró. Tin perovskite solar cells with > 1,300 h of operational stability in n2

through a synergistic chemical engineering approach. Joule, 6(4):861–883, 2022.

[47] S. Sarang, H. Ishihara, Y.-C. Chen, O. Lin, A. Gopinathan, V. C. Tung, and S. Ghosh.

Low temperature excitonic spectroscopy and dynamics as a probe of quality in hy-brid perovskite thin films. Physical Chemistry Chemical Physics, 18:28428–28433, 2016.

[48] C. Chen, X. Hu, W. Lu, S. Chang, L. Shi, L. Li, H. Zhong, and J.-B. Han. Elucidating the phase transitions and temperature-dependent photoluminescence of MAPbBr 3 single crystal. Journal of Physics D: Applied Physics, 51(4):045105, 2018.

[49] W. J. Sarjeant, I. W. Clelland, and R. A. Price. Capacitive components for power electronics. Proceedings of the IEEE, 89(6):846–855, 2001.

1

[50] P. Brochu and Q. Pei. Advances in dielectric elastomers for actuators and artificial muscles. Macromolecular Rapid Communications, 31(1):10–36, 2010.

[51] B. Neese, B. Chu, S.-G. Lu, Y. Wang, E. Furman, and Q. M. Zhang. Large electrocal-oric effect in ferroelectric polymers near room temperature. Science, 321(5890):

821–823, 2008.

[52] S.-G. Lu and Q. Zhang. Electrocaloric materials for solid-state refrigeration. Ad-vanced Materials, 21(19):1983–1987, 2009.

[53] L. Zhu. Exploring strategies for high dielectric constant and low loss polymer dielec-trics, 2014.

[54] R. S. Gebhardt, P. Du, A. Peer, M. Rock, M. R. Kessler, R. Biswas, B. Ganapathysub-ramanian, and S. Chaudhary. Utilizing wide band gap, high dielectric constant nan-oparticles as additives in organic solar cells. The Journal of Physical Chemistry C, 119(42):23883–23889, 2015.

[55] M. Engel, D. Schaefer, D. Erni, N. Benson, and R. Schmechel. Reduced coulomb interaction in organic solar cells by the introduction of inorganic high-k nanostruc-tured materials. Physica Status Solidi (A), 210(9):1712–1718, 2013.

[56] K. M. Noone, S. Subramaniyan, Q. Zhang, G. Cao, S. A. Jenekhe, and D. S. Ginger.

Photoinduced charge transfer and polaron dynamics in polymer and hybrid photo-voltaic thin films: Organic vs inorganic acceptors. The Journal of Physical Chemistry C, 115(49):24403–24410, 2011.

[57] Z. Li, L. A. Fredin, P. Tewari, S. A. DiBenedetto, M. T. Lanagan, M. A. Ratner, and T. J.

Marks. In situ catalytic encapsulation of core-shell nanoparticles having variable shell thickness: Dielectric and energy storage properties of high-permittivity metal oxide nanocomposites. Chemistry of Materials, 22(18):5154–5164, 2010.

[58] Y. Bai, Z.-Y. Cheng, V. Bharti, H. S. Xu, and Q. M. Zhang. High-dielectric-constant ceramic-powder polymer composites. Applied Physics Letters, 76(25):3804–3806, 2000.

[59] H.-P. Xu, Z.-M. Dang, M.-J. Jiang, S.-H. Yao, and J. Bai. Enhanced dielectric prop-erties and positive temperature coefficient effect in the binary polymer composites with surface modified carbon black. Journal of Materials Chemistry, 18:229–234, 2008.

[60] Z.-M. Dang, L. Wang, Y. Yin, Q. Zhang, and Q.-Q. Lei. Giant dielectric permittiv-ities in functionalized carbon-nanotube/ electroactive-polymer nanocomposites.

Advanced Materials, 19(6):852–857, 2007.

[61] T. Hanemann, B. Schumacher, and J. Haußelt. Tuning the dielectric constant of polymers using organic dopants. Microelectronic Engineering, 87(4):533 – 536, 2010.

1

[62] S. Y. Leblebici, T. L. Chen, P. Olalde-Velasco, W. Yang, and B. Ma. Reducing exciton binding energy by increasing thin film permittivity: An effective approach to en-hance exciton separation efficiency in organic solar cells. ACS Applied Materials &

Interfaces, 5(20):10105–10110, 2013.

[63] X. Liu, K. S. Jeong, B. P. Williams, K. Vakhshouri, C. Guo, K. Han, E. D. Gomez, Q. Wang, and J. B. Asbury. Tuning the dielectric properties of organic semicon-ductors via salt doping. The Journal of Physical Chemistry B, 117(49):15866–15874, 2013.

[64] C.J.F. Böttcher. In Theory of Electric Polarization (Second Edition), pages 1 – 8. El-sevier, Amsterdam, 1973. ISBN 978-0-444-41019-1.

[65] H. M. Heitzer, T. J. Marks, and M. A. Ratner. Computation of dielectric response in molecular solids for high capacitance organic dielectrics. Accounts of Chemical Research, 49(9):1614–1623.

[66] K. Maex, M. R. Baklanov, D. Shamiryan, F. lacopi, S. H. Brongersma, and Z. S. Yan-ovitskaya. Low dielectric constant materials for microelectronics. Journal of Ap-plied Physics, 93(11):8793–8841, 2003.

[67] H. D. de Gier, R. Broer, and R. W. A. Havenith. Non-innocent side-chains with di-pole moments in organic solar cells improve charge separation. Physical Chemistry Chemical Physics, 16:12454–12461, 2014.

[68] H. D. de Gier, B. J. Rietberg, R. Broer, and R. W. A. Havenith. Influence of push-pull group substitution patterns on excited state properties of donor-acceptor co-monomers and their trimers. Computational and Theoretical Chemistry, 1040:202–

211, 2014.

[69] H. D. de Gier, F. Jahani, R. Broer, J. C. Hummelen, and R. W. A. Havenith. Prom-ising Strategy to Improve Charge Separation in Organic Photovoltaics: Installing Permanent Dipoles in PCBM Analogues. Journal of Physical Chemistry A, 120(27):

4664–4671, 2016.

[70] M. Breselge, I. Van Severen, L. Lutsen, P. Adriaensens, J. Manca, D. Vanderzande, and T. Cleij. Comparison of the electrical characteristics of four 2,5-substituted poly(p-phenylene vinylene) derivatives with different side chains. Thin Solid Films, 511-512:328 – 332, 2006.

[71] M. Lenes, F. B. Kooistra, J. C. Hummelen, I. Van Severen, L. Lutsen, D. Vanderzande, T. J. Cleij, and P. W. M. Blom. Charge dissociation in polymer:fullerene bulk hetero-junction solar cells with enhanced permittivity. Journal of Applied Physics, 104(11):

114517, 2008.

[72] W.-H. Chang, J. Gao, L. Dou, C.-C. Chen, Y. Liu, and Y. Yang. Side-chain tunability via triple component random copolymerization for better photovoltaic polymers.

Advanced Energy Materials, 4(4):1300864, 2014.

1

[73] S. Torabi, F. Jahani, I. Van Severen, C. Kanimozhi, S. Patil, R. W.A. Havenith, R. C.

Chiechi, L. Lutsen, D. J. M. Vanderzande, T. J. Cleij, J. C. Hummelen, and L. J. A.

Koster. Strategy for enhancing the dielectric constant of organic semiconductors without sacrificing charge carrier mobility and solubility. Advanced Functional Ma-terials, 25(1):150–157, 2015.

[74] B. Meng, H. Song, X. Chen, Z. Xie, J. Liu, and L. Wang. Replacing alkyl with oligo(ethylene glycol) as side chains of conjugated polymers for closeπ–π stacking.

Macromolecules, 48(13):4357–4363, 2015.

[75] X. Chen, Z. Zhang, Z. Ding, J. Liu, and L. Wang. Diketopyrrolopyrrole-based conjug-ated polymers bearing branched oligo(ethylene glycol) side chains for photovoltaic devices. Angewandte Chemie International Edition, 55(35):10376–10380, 2016.

[76] P. Verstappen, J. Kesters, W. Vanormelingen, G. H. L. Heintges, J. Drijkonin-gen, T. Vangerven, L. Marin, S. Koudjina, B. Champagne, J. Manca, L. Lutsen, D. Vanderzande, and W. Maes. Fluorination as an effective tool to increase the open-circuit voltage and charge carrier mobility of organic solar cells based on poly(cyclopenta[2,1-b:3,4-b]dithiophene-alt-quinoxaline) copolymers. Journal of Materials Chemistry A, 3:2960–2970, 2015.

[77] P. Yang, M. Yuan, D. F. Zeigler, S. E. Watkins, J. A. Lee, and C. K. Luscombe. Influence of fluorine substituents on the film dielectric constant and open-circuit voltage in organic photovoltaics. Journal of Materials Chemistry C, 2:3278–3284, 2014.

[78] Y. Sun, S.-C. Chien, H.-L. Yip, K.-S. Chen, Y. Zhang, J. A. Davies, F.-C. Chen, B. Lin, and A. K.-Y. Jen. Improved thin film morphology and bulk-heterojunction solar cell performance through systematic tuning of the surface energy of conjugated polymers. Journal of Materials Chemistry, 22:5587–5595, 2012.

[79] G. Zhang, T. M. Clarke, and A. J. Mozer. Bimolecular recombination in a low bandgap polymer:pcbm blend solar cell with a high dielectric constant. The Journal of Physical Chemistry C, 120(13):7033–7043, 2016.

[80] F. Jahani, S. Torabi, R. C. Chiechi, L. J. A. Koster, and J. C. Hummelen. Fullerene derivatives with increased dielectric constants. Chemical Communications, 50(73):

10645–10647, 2014.

[81] S. Zhang, Z. Zhang, J. Liu, and L. Wang. Fullerene Adducts Bearing Cyano Moiety for Both High Dielectric Constant and Good Active Layer Morphology of Organic Photovoltaics. Advanced Functional Materials, 26(33):6107–6113, 2016.

[82] J. E. Donaghey, A. Armin, P. L. Burn, and P. Meredith. Dielectric constant enhance-ment of non-fullerene acceptors via side-chain modification. Chemical Commu-nications, 51:14115–14118, 2015.

[83] W. Zhao, S. Li, H. Yao, S. Zhang, Y. Zhang, B. Yang, and J. Hou. Molecular optim-ization enables over 13% efficiency in organic solar cells. Journal of the American Chemical Society, 139(21):7148–7151, 2017.

1

[84] X. Liu, B. Xie, C. Duan, Z. Wang, B. Fan, K. Zhang, B. Lin, F. J. M. Colberts, W. Ma, R. A. J. Janssen, F. Huang, and Y. Cao. A high dielectric constant non-fullerene ac-ceptor for efficient bulk-heterojunction organic solar cells. Journal of Materials Chemistry A, 6:395–403, 2018.

[85] X. Xu, Z. Li, J. Wang, B. Lin, W. Ma, Y. Xia, M. R. Andersson, R. A. J. Janssen, and E. Wang. High-performance all-polymer solar cells based on fluorinated naph-thalene diimide acceptor polymers with fine-tuned crystallinity and enhanced dielectric constants. Nano Energy, 45:368–379, 2018.

[86] Y. Cui, Y. Xu, H. Yao, P. Bi, L. Hong, J. Zhang, Y. Zu, T. Zhang, J. Qin, J. Ren, Z. Chen, C. He, X. Hao, Z. Wei, and J. Hou. Single-Junction Organic Photovoltaic Cell with 19% Efficiency. Advanced Materials, 33(41):2102420, 2021.

[87] Z. Zheng, J. Wang, P. Bi, J. Ren, Y. Wang, Y. Yang, X. Liu, S. Zhang, and J. Hou. Tandem organic solar cell with 20.2% efficiency. Joule, 6(1):171–184, 2022.

1

2

A B RIEF O VERVIEW OF F LUORINATION M ETHODS

Abstract: The introduction of fluorine into organic compounds is a powerful tool for al-tering their properties. The rapid development of fluororganic compounds requires the use of right tools and techniques, and it is often difficult to pick the correct approach from a boundless amount of literature sources. We try to highlight important fluorination re-agents, and manners of their application based on three categories: direct fluorination, polyfluoroalkylation, and the fluorinated synthon approach.

The contents of this chapter are based on my BSc and MSc theses. I would like to thank Maksym Bugera, Igor Gerus and Karen Tarasenko for supervision, sharing their knowledge, and engaging my interest in this subject.

2.1. I

NTRODUCTION

Fluorine is the 13thmost abundant element in Earth’s crust [1]. Despite such a high rank-ing, there are not too many compounds in nature that contain this element. Indeed, there are about five major mineral sources of fluorine [1,2], while its overall mineral di-versity is limited to 378 species [3]. Just as well, the number of organofluorines occurring in nature, while being subject to change in view of continuous exploration, still pales in comparison to other organohalogen compounds. A report from 2001 stated 3650 as a total of natural organohalides, of which organofluorines are only 30 [4], and this propor-tion is not likely to have drastically changed since.

While lacking in a variety of natural sources, what fluorine does possess is the par-ticular set of properties, most notable among which are record electronegativity (4.0 out of 4.0 possible), small atomic radius (1.35Å vs. 1.20Å for hydrogen), and large ionization potential (surpassed only by helium and neon)[5]. The combination of these factors sim-ultaneously causes extreme polarization and short bond length of C-F bond (depending on hybridization it can be 1.34 - 1.39Å vs. 1.08 - 1.09Å for C-H bond) [6].

As can be seen from the above-mentioned parameters, this story is prompting to draw comparison with the way replacing hydrogen with fluorine affects organic mo-lecules. And indeed, there are drastic consequences to such change: enhanced thermal stability, increased lipophilicity, mimicry of C-H bond, which in turn leads to modi-fication of chemical reactivity and causes blocking effect in metabolic transformations [2,5,7–9]. These effects lead to increasing interest in the development and application of organofluorine compounds for pharmaceuticals, agrochemicals, surfactants, and poly-meric materials [10].

In fact, despite the ongoing pandemic, in 2021, the US Food and Drug Administra-tion (FDA) approved 50 new drugs, 31 of which were small molecules (62% of the new drug pipeline), and 10 among them contained fluorine atoms [11]. A similar trend was observed for years in a row, like in 2020, when 13 out of 35 small-molecule drugs con-tained fluorine [12].

While over the last 100 years organofluorine chemistry has seen rapid growth, which sparked the development of numerous reagents, approaches, and techniques, introdu-cing fluorine in a right place and in the right manner often remain challenging. It is often hard to navigate in the sea of literature and to choose the correct fluorination approach for reaching the desired outcome. There is a plethora of comprehensive books and re-views on this topic [5,7,8,13–15], and this chapter is in no way claiming to give complete and straightforward guidelines. Still, we thought it is important to attempt giving a brief overview of existing fluorination methods and to elucidate the general pathways of in-troducing the fluorine moieties into organic scaffolds.

When contemplating the most common methods of introducing fluorine moieties that are reported in the literature, every author tends to group these methods using one of their features, be it fluorine source, bond hybridization, or reaction mechanism.

Each classification has its pros and cons, so we chose to generalize fluorination methods into 3 groups: direct fluorination (which in turn can be sub-categorized by the reac-tion mechanism into nucleophilic, electrophilic, and radical), polyfluoroalkylareac-tion and synthon approach (formation of fluorine-containing compounds from simpler reagents that readily contain desired fluorine moieties) [16–18]. But to simplify the reading, first

2

we will give a short tour of notable common fluorination reagents.

In document University of Groningen Fluorinated Fragments for OPV Ivasyshyn, Viktor Yevhenovych (Page 35-46)