Synlett, Table of Contents Synlett 2019; 30(12): 1371-1376DOI: 10.1055/s-0037-1611764 synpacts © Georg Thieme Verlag Stuttgart · New YorkExpanding the 18F-Radiochemical Space: Synthesis and Applications of 1,1-18F-Difluorinated Alkenes Matthew Tredwell *Recommend Article Abstract Buy Article All articles of this category Abstract The synthesis of 18F-perfluorinated motifs from [18F]fluoride is a non-trivial undertaking as highlighted by the few methods and range of motifs that are known. In this Synpacts article we highlight our recent work on the synthesis and derivatization of 1,1-18F-difluoroalkenes to expand the accessible radiochemical space with fluorine-18. 1 Introduction 2 Overview of the Main Strategies to Access 18F-Perfluorinated Motifs with [18F]Fluoride 3 1,1-18F-Difluoroalkenes 4 Conclusion Key words Key wordsfluorine-18 - radiochemistry - fluorination - gem-difluoroalkenes - perfluorination Full Text References References 1 Harsanyi A, Sandford G. Org. Process Res. Dev. 2014; 18: 981 2a Kniess T, Laube M, Brust P, Steinbach J. Med. Chem. Commun. 2015; 6: 1714 2b van der Born D, Pees A, Poot AJ, Orru RV. A, Windhorst AD, Vugts DJ. Chem. Soc. Rev. 2017; 46: 4709 3 Sanford SM, Scott PJ. H. ACS Cent. Sci. 2016; 2: 128 4 Campbell MG, Mercier J, Genicot C, Gouverneur V, Hooker JM, Ritter T. Nat. Chem. 2017; 9: 1 5 Frost AB, Brambilla M, Exner RM, Tredwell M. Angew. Chem. Int. Ed. 2019; 58: 472 For seminal contributions, see: 6a Angelini G, Speranza M, Shiue C.-Y, Wolf AP. J. Chem. Soc., Chem. Commun. 1986; 924 6b Kilbourn MR, Pavia MR, Gregor VE. Appl. Radiat. Isot. 1990; 41: 823 6c Johnström P, Stone-Elander S. J. Labelled Compd. Radiopharm. 1995; 36: 537 For reviews, see: 7a Brooks AF, Topczewski JJ, Ichiishi N, Sanford MS, Scott PJ. H. Chem. Sci. 2014; 5: 4545 7b Preshlock S, Tredwell M, Gouverneur V. Chem. Rev. 2016; 116: 719 7c Deng X, Rong J, Wang L, Vasdev N, Zhang L, Josephson L, Liang SH. Angew. Chem. Int. Ed. 2019; 58: 2580 8 Lien VT, Riss PJ. BioMed Res. Int. 2014; 380124 9a Riss PJ, Aigbirhio FI. Chem. Commun. 2011; 47: 11873 9b Riss PJ, Ferrari V, Brichard L, Burke P, Smith R, Aigbirhio FI. Org. Biomol. Chem. 2012; 10: 6980 10 Levin MD, Chen TQ, Neubig ME, Hong CM, Theulier CA, Kobylianskii IJ, Janabi M, O’Neil JP, Toste FD. Science 2017; 356: 1272 11a Zheng J, Wang L, Lin JH, Xiao JC, Liang SH. Angew. Chem. Int. Ed. 2015; 54: 13236 11b Zheng J, Cheng R, Lin JH, Yu DH, Ma L, Jia L, Zhang L, Wang L, Xiao JC, Liang SH. Angew. Chem. Int. Ed. 2017; 56: 3196 12 For a detailed study on the synthesis of gem-[18F]difluoroalkenes by isotopic substitution, see: Fawaz MV, Brooks AF, Rodnick ME, Carpenter GM, Shao X, Desmond TJ, Sherman P, Quesada CA, Hockley BG, Kilbourn MR, Albin RL, Frey KA, Scott PJ. H. ACS Chem. Neurosci. 2014; 5: 718 13a Zhang X, Cao S. Tetrahedron Lett. 2017; 58: 375 13b Wang F, Li L, Ni C, Hu J. Beilstein J. Org. Chem. 2014; 10: 344 ; and references therein 14a McDonald IA, Lacoste JM, Bey P, Palfreyman MG. Zreika M. J. Med. Chem. 1985; 28: 186 14b Bennett B, Matagne A, Michel P, Leonard M, Cornet M, Meeus M.-A, Toublanc N. Neurotherapeutics 2007; 4: 117 14c Juncosa JI, Takaya K, Le HV, Moschitto MJ, Weerawarna PM, Mascarenhas R, Liu D, Dewey SL, Silverman RB. J. Am. Chem. Soc. 2018; 140: 2151 15a Amii H, Uneyama K. Chem. Rev. 2009; 109: 2119 15b Chelucci G. Chem. Rev. 2012; 112: 1344 16 Okuyama T, Takino T, Sueda T, Ochiai M. J. Am. Chem. Soc. 1995; 117: 3360 17 Ochiai M, Oshima K, Masaki Y. J. Am. Chem. Soc. 1991; 113: 7059