Editorial pubs.acs.org/CR
Introduction: Fluorine Chemistry positron emission tomography. This latter application culminates with a method allowing for the direct 18F-labeling of peptides with cyclotron-produced 18F-fluoride. From the review of A. Togni and co-workers, the readers will gain insight on two hypervalent iodine compounds developed in the authors’ laboratory for electrophilic trifluoromethylation; these compounds, namely 1-(trifluoromethyl)-1,2-benziodoxol3(1H)-one and trifluoromethyl-1,3-dihydro-3,3-dimethyl-1,2benziodoxole, are now commercially available reagents, that have contributed enormously to invigorate the field of late stage trifluoromethylation. This critical review describes how these reagents are best prepared, activated, and applied for both heteroatom−CF3 and C−CF3 bond construction. Mechanistic consideration enhances this account, distinguishing between Lewis acids, metal, and radicals as activation manifold to induce trifluoromethylation. Complementing Togni’s review on electrophilic trifluoromethylation, X. Liu, C. Xu, M. Wang, and Q. Liu present a piece on trifluoromethyl-triethylsilane and its use in nucleophilic trifluoromethylation mediated or not by transition metals. This is a vast account providing a comprehensive grasp of the impact that this so-called Ruppert−Prakash reagent has made on fluorine synthetic chemistry. The additional section on the most recent developments, that appeared after the paper was submitted, is a clear indicator that this reagent will continue to be abundantly used for the construction of CF3- and CF2containing molecules. Synthetic methods for compounds having SCF3 units on carbon, such as trifluoromethylation, trifluoromethylthiolation, and triflylation, are provided in the manuscript written by N. Shibata and his co-workers. The key characteristics of CF3, OCF3, SCF3, SOCF3, and SO2CF3 are outlined in the introduction followed by an impressive review presenting the various chemistries available to date to install these SCF3 motifs into simple and more functionalized targets. The authors highlight that further developments are necessary, especially toward methods based on C−H functionalization or asymmetric variants for control over stereogenicity. C. Ni and M. Hu follow with a manuscript focusing on the sulfur-based fluorination and fluoroalkylation reagents for organic synthesis. As expected, sulfur tetrafluoride derivatives, sulfonyl fluorides, and sulfonium fluorides appear early in this review followed by sulfur-based perfluoroalkylation reagents for perfluoroalkylation themselves, difluoromethylation, difluoroolefination, and monofluoromethylation. This is another timely account displaying how sulfur and fluorine can be used in synergy to control reactivity. The review of F. D. Toste and co-workers distinguishes itself by discussing the issue of F-stereogenicity using both metalinduced and organocatalytic processes. Advances in catalytic enantioselective fluorination show that the field is dominated by electrophilic fluorination with only a few transformations using
Past advances in research and modern chemistry have advanced understanding of how the distinctive place of fluorine in the periodic table impacts on the structure, reactivity, and function of fluorine-containing molecules. As a result, a large variety of materials, polymers, catalysts, and agrochemical or pharmaceutical drugs contain variously sized and shaped fluorine substituents. The field goes far beyond these advances, since fluorine has played an important role to access fluorine-free molecules and extravagantly per-fluorinated compounds displaying unusual properties. In this thematic issue of Chemical Reviews, several areas are explored, but by no means is the collection of selected papers comprehensive of the recent advances made in the field. To have a fuller appreciation of the impact of fluorine, the readers are invited to get familiar with the properties and use of per-fluorinated organic compounds and fluorinated polymers, the occurrence of man-made fluorinated entities found in the atmosphere, as well as the impact of fluorine substitution in agrochemistry and drug discovery. Much is also known of the effect of fluorine on intermolecular behavior (surfactants) or the chemistry of B, P, S, or halogen fluorides, to name only a few additional facets not covered here. However, researchers new to the field, as well as others actively engaged, will find broad insights on fluorine chemistry with papers selected herein and written by leaders in the field. This issue presents a long awaited review showcasing the utility of tetrafluoroborates and boron trifluoride as nucleophilic fluoride sources. Nucleophilic fluorination complements electrophilic and radical fluorination processes, so the account of S. Davies and co-workers is timely. The iconic Balz−Schiemann reaction leading to aryl fluorides via thermal decomposition of aryldiazonium tetrafluoroborate salts is described first followed by a range of nucleophilic substitution leading to alkenyl fluorides, alkyl fluorides, gem-difluorides, glycosyl fluorides, and α-fluoro carbonyl compounds. Next, the ring-opening fluorinations of strained rings are described followed by addition reactions to alkenes, alkynes, and allenes, and Prins-type cation-π cyclization-fluorinations. T. Ritter and co-workers review next all the “modern carbon− fluorine bond forming reactions” leading to aryl fluorides. The fluorination of arenes is an important area of research, as the fluorine substitution can have drastic effects on their properties and, in the case of drug molecules, can influence how well they are absorbed into the body and how resistant they are to metabolism. This authoritative account updates readers with the most recent approaches toward late stage fluorination of arenes from a range of precursors. D. O’Hagan discusses in full the discovery, structure, and activity of fluorinase enzyme, a remarkable enzyme capable of catalyzing a nucleophilic fluorination process. The emphasis is on enzymatic C−F bond formation followed by a comprehensive account on how the discovery of this unique enzyme has led to various biotechnological developments, including fluorometabolite engineering, the incorporation of fluoroacetyl-CoA and fluoromalonyl-CoA into polyketide frameworks, and the use of fluorinase to access 18F-labeled molecules for applications in © 2015 American Chemical Society
Special Issue: 2015 Fluorine Chemistry Published: January 28, 2015 563
DOI: 10.1021/cr500686k Chem. Rev. 2015, 115, 563−565
Chemical Reviews
Editorial
fluoride sources. In contrast, a diverse range of nucleophilic, electrophilic, and radical processes is represented for mono-, di-, and trifluoromethylation and trifluoromethylthiolation reactions. Late stage fluorination is producing a range of diverse fluorinecontaining compounds that can be used for many purposes, such as further functionalization and the production of catalysts or ligands, materials, or new solvents. The review of S. Fustero, G. Haufe, et al. merges two very active research fields with a very nice piece focused on the olefin metathesis reactions with fluorinated substrates, catalysts, and solvents. While the selective introduction of one fluorine atom (or two or three) remains a challenge, the contrary, namely changing a C−F bond into C−C or C−H bonds, even C−S and C−O bonds, is a useful method, since perfluorinated units, especially aromatic ones, are often readily available. These reactions, preferably in a catalytic manner, are summarized by the group of T. Braun. The synthesis and reactivity of polyfluorinated ethanes (PFE) is comprehensively reviewed in the piece of Nenajdenko and coworkers. The material is organized with a description of the various approaches known to prepare PFE followed by a discussion classifying their transformations into finer chemicals. The review concludes with applications in medicinal chemistry In an overview about perfluoroalkyl-fullerenes by O. Boltalina, S. Strauss, and co-workers it is shown that this class of compounds may be now the best developed kind of substituted fullerenes. One main advantage of these is that fullerene cages that are insoluble and nonvolatile can be changed into soluble and volatile forms, so that their identity can be established. Since organofluorine compounds are almost completely absent in vivo, the introduction of ingredients containing fluorine can be monitored by Magnetic Fluorine Imaging (MRI), making use of the highly sensitive magnetic resonance effect: G. Resnati and co-workers. This method will certainly expand in the future. The SF5-group is in some aspects a better alternative for the CF3-group. The chemistry with this group fascinates researchers worldwide. But the use of compounds containing the SF5-group in pharmacy, agro-chemistry, and technology is just at the beginning, since even the introduction of the group into organic systems remains a challenge, as can be verified in the comprehensive review by P. Savoie and J. Welch. The making, structural description, and use of solid state fluorides, a traditional field, is comprehensively collected by A. Tressaud and co-workers. It is a safe prediction that the presently already enormous use of such compounds will strongly grow in the future. J. Haner and G. Schrobilgen describe the advances in xenon IV chemistry. This oxidation state has in past times played a minor role in noble gas chemistry, but more recently an enormous growth of knowledge has arrived. This topic exemplifies the fact that certain classes of compounds can only be made with fluorine, as is the case not only for noble gas compounds. Molecular hexafluorides are a unique class. These 15 or more compounds are very much alike in physical aspects, but their chemical behavior varies strongly. Their bonding situation is still a subject for theoretical discussions. The use as extremely potent oxidizers of some of them should be more recognized by the general chemical community (K. Seppelt).
AUTHOR INFORMATION Corresponding Authors
*E-mail:
[email protected]. *E-mail:
[email protected]. Notes
Views expressed in this editorial are those of the author and not necessarily the views of the ACS. Biographies
Veronique Gouverneur is Professor of Chemistry at Oxford University. After a PhD in chemistry at the UCL (Belgium), she moved to the Scripps Research Institute (USA) to gain expertise in the area of biological chemistry. She started her independent research career at the University of Oxford in 1998 with a program on late stage fluorination approaches to address long-standing problems in the synthesis of fluorinated analogues of natural products, pharmaceutical drugs and molecular probes for PET imaging. Her team performed the first [18F] labeling experiments in Oxford in a facility built in the chemistry department. Her work (> 150 peer-reviewed research papers) recognized by numerous international awards (more recently the ACS Award for creative work in fluorine chemistry), is supported by the EPSRC, BBSRC and MRC grants in addition to extensive funding from the EC and Pharma. She is currently holding the prestigious Chair Blaise Pascal (2012-2014) funded by the ENS (Paris). Since her appointment in Oxford, she also holds a tutorial fellowship at Merton College Oxford where she teaches organic and biological chemistry.
Konrad Seppelt, born 1944 in Leipzig, Germany, obtained the PhD in Chemistry at the Heidelberg University. In 1980 he moved to the Free University Berlin as full professor. In his entire career he worked in the field of fluorine chemistry, focusing on the preparation of unknown or unstable inorganic and organic fluorine compounds. Also he kept an interest in principal organometallic and organometalloid compounds.
Veronique Gouverneur* Konrad Seppelt* Freie Universitaet, Chemistry 564
DOI: 10.1021/cr500686k Chem. Rev. 2015, 115, 563−565
Chemical Reviews
Editorial
He is author of about 340 papers and held a similar number of national and international lectures. He was awarded a number of prizes, among others the Award for creative work in fluorine chemistry by the American Chemical Society.
565
DOI: 10.1021/cr500686k Chem. Rev. 2015, 115, 563−565
