Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• DMSO (Scheme 12) [45]. In this case, the reaction works well under metal-free conditions using iodine as the catalyst. Remarkably, the activation of DMSO was accomplished using Selectfluor, and in this case, DMSO is the source of a C-1 unit. It is important to note that the reaction could be performed

• to the resulting compounds. Once again, DMSO was confirmed as the origin of the methylene bridge by isotope labelling experiments using DMSO-d6. The proposed mechanism comprises the activation of DMSO by a Ru(III) catalyst and the role of Selectfluor working as the oxidant that allows the "activation

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• -workers (Scheme 16) [39]. p-TolIF2 is formed in situ from p-iodotoluene and Selectfluor in a 4.5:1 HF:amine solution, which is obtained by combining Et3N·3HF and pyridine·HF. A range of N-allyl carboxamides 31 were successfully cyclised forming fluoromethyl-2-oxazolines 32 in good yields. The synthesis of

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• another important transformation via anodic oxidation realized by the Baran group [36]. The choice of Selectfluor, which plays multiple roles, was crucial. In addition to functioning as a fluorine source, Selectfluor also acts as a mediator similar to quinuclidine and serves as an electrolyte. The method

• was demonstrated to be scalable for natural products such as sclareolide and protected ʟ-valine. The proposed mechanism involves a radical chain process. Initiation occurs by nitrate-mediated or direct electrochemical anodic oxidation, followed by fluorination with Selectfluor. After fluorination, the

• Selectfluor reagent abstracts a hydrogen atom from the substrate, which can then undergo further fluorination. The nitrate additive proved helpful as an initiator but is not necessary for certain substrates like sclareolide and protected ʟ-valine (Scheme 26). An electrochemical C(sp3)–H cyanation for LSF was

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• one diastereomer of 7q was formed (Scheme 4). This result is in accordance with the calculated mechanism. The more electron-rich trisubstituted alkene 3r reacted directly with Selectfluor leading to a tertiary carbocation which was trapped by acetonitrile in a Ritter-type process to generate bisamide

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• of the oxidative conditions used (mCPBA [75], H2O2 [75], selectfluor®/H2O [76], SO2Cl2/NaHCO3 (aq) [77][78]), in most cases a complex mixture was observed and no corresponding vinylic compound was detected by NMR. The phenylselenyl moiety could also undergo radical reduction to produce

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

• fluorinating reagents, such as diethylaminosulfur trifluoride (DAST), HF, CsF, and AgF has been established as a reliable method. Electrophilic fluorinating reagents, such as 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor), N-fluorobenzenesulfonimide, and

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• investigate hypervalent iodine(V) fluorides has been limited primarily by their difficult preparation traditionally using harsh fluorinating reagents such as trifluoromethyl hypofluorite and bromine trifluoride. Here, we report a mild and efficient route using Selectfluor to deliver hypervalent iodine(V

• ; fluorobenziodoxoles; halogen bonding; hypervalent iodine; Selectfluor; Introduction An important strategy in the drug discovery process is the incorporation of fluorine into biologically active molecules because fluorine can improve bioactivity and pharmacokinetic properties [1]. Consequently, 22% of all small

• as Selectfluor (Scheme 1B) [12][13][14][15][16][17][18][19][20]. In contrast to the chemistry of hypervalent iodine(III) reagents, very little is known about hypervalent iodine(V) fluorides. One problem that has blocked research into these compounds has been the lack of synthetic procedures to access

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• subsequently attack electrophilic Selectfluor to afford the benzyl fluoride (Figure 2) [34]. The methodology was demonstrated on eight para-substituted benzylic substrates. The authors noted that resubjecting the monofluorinated compound 1 to the same reaction conditions afforded the difluorinated compound 2

• monofluorination of tertiary benzylic C(sp3)–H bonds adjacent to nitro groups was reported by Loghmani-Khouzani and co-workers in 2006, in which ammonium acetate and Selectfluor were employed under sonochemical conditions to effect the fluorination (Figure 3) [35]. The authors noted that the use of sonochemistry

• different functional groups at the 5-position. The Shi group reported the use of Pd(II) and Selectfluor to enable the enantioselective β-fluorination of α-amino acids (Figure 6) [40]. The presence of 2-(pyridin-2-yl)isopropylamine (PIP) as directing group was essential for the formation of a four-coordinate

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• rearrangement using benzonorbornadiene and the chiral natural compound (+)-camphene as bicyclic alkenes, selectfluor as an electrophilic fluorine source, and water and various alcohols as nucleophile sources. The structure of bicyclic oxy- and alkoxyfluorine compounds was determined by NMR and QTOF-MS analyses

• . Keywords: alkoxyfluorine compounds; bicyclic alkene; oxyfluorination; selectfluor; Wagner–Meerwein rearrangement; Introduction Organofluorines are of great importance in the pharmaceutical and agrochemical industries, as the presence of fluorine has a serious effect on the biological activities of organic

• alkenes. We previously developed a dihomohalogenation method using selectfluor as an oxidant [27]. Herein, we synthesized bicyclic oxy- and alkoxyfluorine compounds using selectflour as an electrophilic fluorination reagent, water and various alcohols as an nucleophile. Results and Discussion In this

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• catalysis, which often involves the catalytic use of an iodoarene with stoichiometric oxidants such as MCPBA, Selectfluor, etc. [18][19][20]. Earlier and recent hypervalent iodine-catalyzed olefin halofunctionalizations by several groups have predicated on the use of intramolecular olefin substrates

• hypervalent iodine catalyst precursor, Selectfluor as the oxidant, and LiBF4 as the lithium salt for hypervalent iodine activation, we were gratified to observe the formation of the desired oxazoline 3 in 59% yield as the major regioisomer in nitromethane (MeNO2) solvent (Table 1, entry 1). To further improve

• α-phenylstyrene produced the respective oxazoline products with high regioselectivity and reasonable yields using iodoanisole as the catalyst precursor (Figure 3, products 24 and 25). The proposed catalytic cycle (Figure 4) begins with iodotoluene A which is oxidized by Selectfluor salt into the

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• agents offers an alternative fluorination route, for example, the reactions of MeCN solutions of 1,3-diketones with electrophilic fluorinating agents such as Selectfluor eventually give the corresponding 2,2-difluoro-1,3-diketone derivatives [12]. Monofluorination of the 1,3-diketone substrates is rapid

• , but the second fluorination step occurs only after reaction for several days. In the solid phase, mechanical milling of the diketone substrate with solid Selectfluor in the presence of sodium carbonate [13][14], and reaction of ketones with a strong base and an N–F reagent give rise to the

• corresponding 2,2-difluoroketones [15]. In related kinetic studies concerning the electrophilic 2-fluorination of 1,3-diketones with Selectfluor [16][17], we demonstrated that the rate-determining step for difluorination was enolization of the intermediate 2-fluoro-1,3-diketone. Monofluorination of 1,3

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• bromine source in combination with Selectfluor® (Scheme 1, reaction 3) [29]. Despite significant progress in this area, most of these methodologies still suffer from the use of external oxidants, complex reaction equipment, and expensive and/or toxic halogen sources, which limit the practicality for large

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• conditions, without transition metal catalysts, added oxidants, or strong acids involved, using Selectfluor (1-(chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane-1,4-diium ditetrafluoroborate) as essential additive [73]. With regard to the reaction medium, the idea of replacing classic organic solvents

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• . In recent years, a Ag-catalyzed cross-dehydrogenative coupling of aromatic C(sp2)–H bonds with ethers has also been developed. In 2018, Wang et al. reported that the AgNO3-promoted CDC of quinaldine (183) with ethers afforded alkylated quinoline derivatives in the presence of selectfluor as a mild

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• year, the group of Huang reported an elegant and straightforward palladium(II)-catalyzed ortho-selective trifluoromethylthiolation of arenes bearing various directing groups using the nucleophilic trifluoromethylthiolating source AgSCF3 in combination with Selectfluor® as oxidant (Scheme 6, 29 examples

• (KIE = 2.7). Subsequently palladacycle C is oxidized by Selectfluor® to form a palladium(IV) complex D. After a ligand exchange with AgSCF3, the intermediate E is obtained, which, after reductive elimination, releases the desired product 12 and regenerates the catalyst. Alternatively, a ligand exchange

• with AgSCF3 occurs before the oxidation step, generating the palladium(II) complex F. After an oxidative addition in the presence of Selectfluor®, the palladium(IV) intermediate E is generated. Finally, after reductive elimination step, the desired product 12 is released and the catalyst regenerated

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• complemented mechanochemical fluorinations carried out with other reagents, such as AgF [16], 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor®) [17][18][19][20], among other fluorinating reagents [21]. However, as shown above, examples using NFSI by mechanochemistry

• example through the reaction of product 2c with the second equivalent of NFSI. In solution, 1,3,5-trimethoxybenzene (1c) has been reported to undergo fluorodemethylation when reacted with Selectfluor®, however the authors mentioned that “the fate of the methyl group lost in the conversion” of 2c to 2c

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• -monohalooxindoles involve the direct halogenation of oxindoles with various reactive halogenating reagents, including N-chloro-N-methoxybenzenesulfonamide [24][25], ammonium halides/oxone [13], Selectfluor® [26][27], and CuBr2 (Scheme 1, reaction 4) [15]. However, these protocols each have a certain scope and

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• also been reported for the direct C(sp3)–H fluorination. Chen and co-workers [94] described a fluorination method employing Selectfluor as fluorine source and the commercially available V2O3 to give fluorine-containing compounds under mild conditions and with moderate to good yields (Scheme 10B,C). The

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

• , Grignard reagents, and aromatic compounds under mild conditions. In each case Selectfluor gave the corresponding fluorinated products in good to high yields (Scheme 34). As can be seen in Figure 3 and Figure 4, two years later (1994), Banks et al. reported mono- and difluorinations of various 1,3

• -dicarbonyl compounds using Selectfluor (16-3a) [61]. In 1995, the same group reported that Selectfluor reacted with quinuclidine to form N-fluoroquinuclidinium tetrafluoroborate in quantitative yield [62] (Scheme 35). They described this as a “transfer fluorination” since there was an intermolecular transfer

• of the fluorine atom of Selectfluor to the nitrogen of quinuclidine. In 1996, full details were published on the reactivities of all 16-3 reagents and the syntheses of 16-3 and intermediates 16-2 including additionally C2H5 and C8H17 as R group and PF6− and FSO3− as anion X− [63][64]. The generous

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• introduced bromine atom can be converted into other functional groups. The reaction of 2a with selectfluor in MeCN at 25 °C for 12 h gave fluorinated product 3 in 86% yield (Scheme 4, top) [50]. Allylated product 4 was obtained in 64% yield upon treating 2a with allyltributylstannane in the presence of a

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• 200032, P. R. China 10.3762/bjoc.16.258 Abstract A silver-catalyzed three-component reaction involving alkynes, Selectfluor®, and diethyl phosphite was employed for the one-pot formation of C(sp2)–F and C(sp2)–P bonds to provide an efficient access to β-fluorovinylphosphonates in a highly regio- and

• others concerning the silver-catalyzed phosphonofluorination of alkenes [24][25][26], we herein present a general silver-catalyzed regio- and stereoselective phosphonofluorination of alkynes using Selectfluor® and phosphonates as reactants (Scheme 1). This new silver-catalyzed approach to fluorinated

• vinylphosphonates from simple and commercially available alkynes proceeds under mild conditions with high stereoselectivity, and thus enabling the rapid construction of molecular complexity. Results and Discussion We investigated the reaction of phenylacetylene (1a), Selectfluor®, and diethyl phosphite to afford β

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

• -fluorosaccharinsultam. The most recent discovery of an advanced electrophilic fluorinating agent was Selectfluor® (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)) [190]. Selectfluor® [190][191] is a nonhygroscopic, crystalline solid, stable at temperatures up to 195 °C, nonhazardous

• [192], reliable and commercially available [193]. Selectfluor® is synthesized on a multiton p.a. scale in a simple and efficient method (Scheme 3) [193]. The precursor 24 is prepared by alkylation of DABCO (1,4-diazabicyclo[2.2.2]octane) with DCM. A counterion exchange with NaBF4 causes NaCl

• precipitation in MeCN, and the fluorination with F2 in the presence of sodium tetrafluoroborate affords Selectfluor®. Moreover, by variation of these conditions, different derivatives of Selectfluor® (e.g., a methyl derivative: Selectfluor® II and a 2,2,2-trifluoroethyl derivative) with different physical

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• desired fluorinated product 12a. Thus, according to this synthetic and mechanistic path, the N-fluorocinchona intermediate acted as an asymmetric electrophilic fluorinating agent. Conducting the fluorination of 8a with a quinine (Q)/Selectfluor combination in different solvents revealed chloroform as a

• the analogous reactions with Selectfluor. Having these results in hand, we moved to investigating the scope and limitation of this procedure with the Ugi adducts 8 obtained previously (Table 4). In order to have a more balanced representation we decided to test most of these substrates 8 with eight