Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• brought about a breakthrough in synthetic fluorine chemistry enabling an increasing number of researchers to engage in organofluorine chemistry. Their development has significantly contributed towards the current ‘golden age’ of fluorine chemistry. The N-F fluorinating agents now stand out as particularly

Organo-fluorine chemistry V

• David O’Hagan

Beilstein J. Org. Chem. 2021, 17, 737–738, doi:10.3762/bjoc.17.63

• David O'Hagan School of Chemistry, Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, United Kingdom 10.3762/bjoc.17.63 Keywords: Organo-fluorine chemistry; This is the fifth thematic issue on organo-fluorine chemistry in the Beilstein Journal

• Beilstein Journal of Organic Chemistry has become a settled home for papers in contemporary organo-fluorine chemistry. Authors have presented their recent findings or, in some cases, reviewed important areas, from bioactives to materials, and collectively the papers highlight the vibrancy and range of

• activity associated with this theme. Organo-fluorine chemistry merits our attention as an important discipline within contemporary organic chemistry contributing in a unique way to innovation and performance in the development of functional molecules. This issue will be historically memorable as all of the

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• group is an important task. During our research in the field of fluorine chemistry, we have previously developed methods to get convenient access to CF3-containing propargylic alcohols 1 using 2-bromo-3,3,3-trifluoropropene [4][5] as well as 1-chloro-3,3,3-trifluoropropene [6] as a substrate and to

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• shown in Scheme 2 [45]. This study had a large impact on fluorine chemistry in terms of the availability of halothane to build difluoroalkyl ethers. However, these reactions have significant drawbacks such as the need of harsh reaction conditions, low chemical yields, and in particular, very few

Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent

• Tatsuhiro Uchikura,
• Nanami Kamiyama,
• Taisuke Ishikawa and
• Takahiko Akiyama

Beilstein J. Org. Chem. 2020, 16, 2442–2447, doi:10.3762/bjoc.16.198

• ; catalysis; copper; fluorine chemistry; trifluoromethylation; Introduction The introduction of a trifluoromethyl group is one of the most attractive reactions in drug discovery [1][2]. In the past decade, trifluoromethylation reactions of aryl halides in the presence of transition-metal complexes were

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• molecules using copper-based fluorinated reagents will be given. Keywords: copper; difluoromethylation; fluorinated reagents; fluorine chemistry; synthetic methodologies; Introduction In a society in which fluorinated molecules are playing a pivotal role in pharmaceutical and agrochemical industries as

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• , Qingdao 266000, China University of Chinese Academy of Sciences, Beijing 100049, China State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, China 10.3762/bjoc.15.218 Abstract Fluorine chemistry plays an increasingly important role in pharmaceutical

• stoichiometric amounts and/or toxic reagents [14]. Also, low functional group tolerance, being limited to activated arenes, the production of metal salts as stoichiometric byproducts, and poor levels of regioselectivity would always be observed, limiting the progress of fluorine chemistry to some extent. In this

• -catalyzed fluorination/fluoroalkylation reactions represent an important and hot topic in fluorine chemistry. In addition, among the various metals developed, palladium is the most commonly employed transition metal, followed by copper owing to its high efficiency and cheapness. Meanwhile, other transition

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• azobenzenes with different halogen bonding donor properties are discussed in relation to their changing photophysical properties, rationalized by DFT calculations. Keywords: azobenzene; DFT calculations; fluorine chemistry; halogen bonding; photochemistry; Introduction The halogen bond is an attractive

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• ; pentafluorosulfanyl; Introduction There has been a surge in the number of reports about fluorine chemistry in recent decades. This is because fluorine is an extremely important element whose presence in a compound can completely change its original physical and chemical characteristics [1][2][3]. The chemical

Supramolecular chemistry: from aromatic foldamers to solution-phase supramolecular organic frameworks

• Zhan-Ting Li

Beilstein J. Org. Chem. 2015, 11, 2057–2071, doi:10.3762/bjoc.11.222

• Fluorine Chemistry for a master’s degree. The lab is well-known for its longstanding research on reactions of fluorine-containing molecules. Professor Chi left as a visiting scholar at the University of Fribourg, Switzerland shortly after I joined the group and I was actually advised by Professor Yong-Da

• laboratory. Using them to prepare new macrocycles became a small independent dissertation project for me. In 1990, I joined Professor Qing-Yun Chen’s group as a Ph.D. candidate. Professor Chen is a distinguished, esteemed Chinese chemist in organic fluorine chemistry. His group developed new

• trifluoromethylation reagents, which found many practical applications [3]. I respect him for his persistent passion for science. Even at the age of 86 in 2015, he still goes to his office and advises his students and remains active in the field of fluorine chemistry. I received my Ph.D. degree in December of 1992. My

The difluoromethylene (CF₂) group in aliphatic chains: Synthesis and conformational preference of palmitic acids and nonadecane containing CF₂ groups

• Yi Wang,
• Ricardo Callejo,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2014, 10, 18–25, doi:10.3762/bjoc.10.4

• in the extended anti-zig-zag chain and suggests a design modification for long chain aliphatics which can introduce conformational stability. Keywords: difluoromethylene; fatty acids; fluorination; organic fluorine chemistry; organo-fluorine; palmitic acid; Introduction The selective replacement of

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• synthesis and reactions of fluorine-containing molecules by the use of flow microreactor systems to overcome long-standing problems in fluorine chemistry. Keywords: defluorination; fluorine; fluorination; flow microreactor; organo-fluorine; perfluoroalkylation; Review Fluorine is a key element in the

• fluorine chemistry. Meanwhile, flow microreactor synthesis, the use of microfluidic devices, has emerged as a new method for producing chemical substances with high efficiency [11][12][13]. Now, the introduction of continuous-flow synthesis technique to laboratory synthesis represents a highly useful and

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• formation has become a landmark achievement in fluorine chemistry. This rapidly growing research field has been the subject of some excellent reviews. Our approach focuses exclusively on transition metal-catalyzed reactions that allow the introduction of –CFH2, –CF2H, –CnF2n+1 and –SCF3 groups onto sp

Organo-fluorine chemistry III

• David O'Hagan

Beilstein J. Org. Chem. 2013, 9, 2180–2181, doi:10.3762/bjoc.9.255

• David O'Hagan School of Chemistry, University of St Andrews, Fife, KY16 9ST, United Kingdom 10.3762/bjoc.9.255 Keywords: organo-fluorine; It is a pleasure to introduce the 3rd in the series of Thematic Issues on organo-fluorine chemistry for the Beilstein Journal of Organic Chemistry (BJOC

• ). These series have become progressively more successful over time in terms of the number and quality of the contributions received. It is also pleasing to note that the profile and impact factor of the journal has increased steadily over this time as well. Organo-fluorine chemistry is enjoying a high

• contributions in the Thematic Series focus on this aspect of organo-fluorine chemistry. Fluorine touches all categories of performance compounds extending from bioactives to organic materials, and society demands continual improvements in the quality and performance of products and devices. As the global

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• –fluorine or oxo–fluorine exchange. Keywords: amino acids; epoxidation; fluorination; hydroxylation; stereoselective reaction; Introduction Fluorine chemistry is an expanding area of research that has generated increasing interest in pharmaceutical and medicinal chemistry in recent years because of its

The preferred conformation of erythro- and threo-1,2-difluorocyclododecanes

• Yi Wang,
• Peer Kirsch,
• Tomas Lebl,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2012, 8, 1271–1278, doi:10.3762/bjoc.8.143

• –F bond endo into the ring, and appear to benefit from C–CHF–C angle widening, which relaxes 1,4-H,H transannular interactions. Keywords: alicyclic chemistry; conformational analysis; cyclododecane; 19F NMR; organo-fluorine chemistry; transannular interactions; Introduction The conformation of

Prins fluorination cyclisations: Preparation of 4-fluoro-pyran and -piperidine heterocycles

• Guillaume G. Launay,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2010, 6, No. 41, doi:10.3762/bjoc.6.41

• . Keywords: 4-fluoropiperidine; 4-fluoropyran; heterocycles; organo-fluorine chemistry; Prins cyclisation; Introduction Selective incorporation of the C–F bond into organic molecules can impart useful and attractive properties to performance materials [1][2][3]. To this end there are a useful but relatively

The C–F bond as a conformational tool in organic and biological chemistry

• Luke Hunter

Beilstein J. Org. Chem. 2010, 6, No. 38, doi:10.3762/bjoc.6.38

• flexible. In order to gain information about the bioactive conformation, fluorine chemistry can be used to modify the peptides’ conformational behaviour. For example, there is an interesting contrast between the enkephalin-related peptide derivative 64 and its fluorinated analogue 65 (Figure 17) [51][52

Organo-fluorine chemistry II

• David O'Hagan

Beilstein J. Org. Chem. 2010, 6, No. 36, doi:10.3762/bjoc.6.36

• David O'Hagan School of Chemistry, University of St Andrews, Fife, KY16 9ST, United Kingdom 10.3762/bjoc.6.36 It is a pleasure to be able to introduce this second Thematic Series on ‘organo-fluorine chemistry’ within the Beilstein Journal of Organic Chemistry. The series now embeds the subject

• firmly as a special interest area of the journal. The first series in 2008 presented contributions representing a wide range of organic fluorine chemistry [1][2][3][4][5][6][7][8][9][10] and this series continues that trend exploring the synthesis and properties of a new range of organo-fluorine

Three step synthesis of single diastereoisomers of the vicinal trifluoro motif

• Vincent A. Brunet,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2009, 5, No. 61, doi:10.3762/bjoc.5.61

• diastereoisomeric series of this motif. The route is a significant improvement on an earlier six step strategy. Keywords: C–F bond; organo–fluorine chemistry; stereospecific fluorination; vicinal trifluoro motif; Introduction Selective fluorination is an important strategy for the design of performance molecules

Themed series in organo- fluorine chemistry

• David O'Hagan

Beilstein J. Org. Chem. 2008, 4, No. 11, doi:10.3762/bjoc.4.11

• David O'Hagan School of Chemistry, University of St Andrews, Fife, KY16 9ST 10.3762/bjoc.4.11 It is a great pleasure to be able to introduce this Themed series on organo-fluorine chemistry in the Beilstein Journal of Organic Chemistry. The introduction of fluorine into organic molecules is widely

• in the area. Contributions to the series come from an international grouping of noted experts in fluorine chemistry and we are delighted that they have agreed to contribute their papers for such a successful launch.

Stereoselective α-fluoroamide and α-fluoro- γ-lactone synthesis by an asymmetric zwitterionic aza-Claisen rearrangement

• Kenny Tenza,
• Julian S. Northen,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2005, 1, No. 13, doi:10.1186/1860-5397-1-13

• fluorine at the stereogenic centre. Introduction The development of methods for the stereoselective introduction of the C-F bond, α-to a carbonyl group has been a significant and recent focus in organo-fluorine chemistry.[1][2] Most effort has involved enolate reactions with electrophilic fluorinating