gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan 10.3762/bjoc.20.194 Abstract gem-Difluorination of carbon–carbon triple bonds was conducted using Brønsted acids, such as Tf2NH and TfOH, combined with Bu4NBF4 as the fluorine source. The electrochemical oxidation of a Bu4NBF4/CH2Cl2 solution

• containing alkyne substrates could also give the corresponding gem-difluorinated compounds (in-cell method). The ex-cell electrolysis method was also applicable for gem-difluorination of alkynes. Keywords: carbon–carbon triple bonds; chemical method; electrochemistry; gem-difluorination; Introduction

• blocks for further transformations. We have focused on the investigation of gem-difluorination of carbon–carbon triple bonds, because this procedure is one of the most simple but powerful and straightforward methods. In addition, there have been a few reports in the literature that seem to mainly rely on

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• from an aspect of green chemistry [7][8][9][10]. In this context, we have developed various electrochemical methodologies for efficient selective fluorination [11][12] and molecular conversion of organofluorine compounds to date [13][14][15][16][17][18]. We have also achieved the gem-difluorination of

• ; (b) o-phthalonitrile (4 mM), and (c) o-phthalonitrile (4 mM) + 1 (8 mM). Scan rate: 100 mV/s. Electrochemical gem-difluorination of sulfides bearing α-electron-withdrawing groups. Electrochemical gem-difluorodesulfurization of dithioacetals. Electrochemical gem-difluorodesulfurization of

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• -difluorination. gem-Difluorination is particularly challenging since the first introduced fluorine atom will electronically hinder the second fluorination at the same position. For difluorination, xanthone was employed as the PC and Selectfluor® II as the fluorine source (Scheme 7). The higher T1 energy may have

• bond dissociation enthalpies (calculated BDEs = 64.0 kcal⋅mol−1) [196]. While the T1 energy of Selectfluor® II is not reported to our knowledge, it is possible that the greater reactivity towards gem-difluorination could stem from it having a T1 energy closer to xanthone. The reaction conditions

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• ) reagents were applied to oxidize transition metals [21][22][23][24][25]. In an alternative way, the electrophilic hypervalent iodine(III) reagents can activate alkenes directly in a metal-free manner. Based on this strategy, dichlorination [26], 1,2-difluorination [27], gem-difluorination [28

• products. Recently, Jacobsen and co-workers reported a highly enantioselective gem-difluorination of various cinnamic acid derivatives through the same oxidative rearrangement (Scheme 16) [68]. During the catalysts screening, they found that the benzylic unit in the catalysts was essential for a high

• aminofluorination of alkenes [62]. Catalytic difluorination of alkenes with Selectfluor [63]. Iodoarene-catalyzed 1,2-difluorination of alkenes [64]. Iodoarene-catalyzed asymmetric fluorination of styrenes [64][65]. Gem-difluorination of styrenes [67]. Asymmetric gem-difluorination of cinnamic acid derivatives [68

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• dithiolane and dithiane protecting groups which are irreplaceable intermediates for the introduction of, e.g., fluorine via gem-difluorination [1][2]. They also allow the formation of valuable building blocks that can be used for diverse transformations in organic chemistry (e.g., Umpolung) [3]. Ketene 1,3

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

• inert plastic flow tubes provided flexibility, scale-up production, and improved safety of operation. Using flow chemistry, the conversion of alcohols to fluorides was achieved by Seeberger and Ley, independently (Scheme 2) [44][45][46][47]. Usually, gem-difluorination of ketones by DAST is known to be

• less efficient because it needs heating and/or long reaction time to complete the fluorination [48][49]. Nevertheless by the use of a flow microreactor device, isatin underwent gem-difluorination to give the corresponding difluoride in 73% yield (residence time in the reactor: within 1 h). Reactions