Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• Selectfluor® and amine/HF mixtures, the formation of protected α-fluoroketones from simple alkynes was realised. Whilst the transient p-TolIF2 species generated in situ productively engaged with pentynyl benzoate scaffolds to generate the desired α-fluoroketone motif, augmentation or contraction of the linker

• fluorinating reagents [44][45]. Developments by Hammond and Xu validated N-pyridine oxides as terminal oxidants to substitute Selectfluor® for the cationic Au(I)/Au(III) cycle, thereby enabling high functional group tolerance [46][47][48][49]. Inspired by these and other selected advances [50][51], in metal

• -based fluorination, a complementary organocatalytic variant [52], based on an I(I)/I(III) catalysis platform was explored (Figure 1C). It was envisaged that the in situ generation of p-TolIF2 via oxidation of p-TolI with Selectfluor® in the presence of an amine/HF complex might enable the title

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Synthesis of new fluorescent molecules having an aggregation-induced emission property derived from 4-fluoroisoxazoles

• Kazuyuki Sato,
• Akira Kawasaki,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2020, 16, 1411–1417, doi:10.3762/bjoc.16.117

• desired fluorinated analog 9b. However, in the synthesis of F-BKIs through the selective fluorination of the corresponding BKIs, the use of 1 equiv of Selectfluor did not give any product and performing the reaction with excess amounts of Selectfluor gave rise to the corresponding α,α-difluorinated

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• isoxazolines 70 was realized [116] by the oxidation of oximes 69 by the Selectfluor/Bu4NI system (Scheme 25). A radical mechanism was proposed in which the hypoiodite formed from the oxime undergoes a homolytic cleavage of the O–I bond with the formation of the iminoxyl radical. As a rule, R1 is an aromatic

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• ] (Scheme 33). 2.7. Photocatalyzed benzylic fluorination of N-phthalimido phenylalanine The photocatalyzed benzylic fluorination of phthalimide-protected phenylalanine methyl ester 145, using the photosensitizer 1,2,4,5-tetracyanobenzene (TCB), and Selectfluor in acetonitrile was carried out using a pen

• LED light source (365 nm) and Selectfluor in MeCN [72]. Alternatively, a visible light (14 Watt CFL) mediated benzylic fluorination of a series of N- and C-terminally protected phenylalanines 147 using Selectfluor and dibenzosuberenone in acetonitrile, afforded the β-fluorophenylalanine derivatives

• diastereoisomeric purity (dr > 99:1) (Scheme 38). 2.9. Direct fluorination of β-methylene C(sp3)−H The direct fluorination of β-methylene C(sp3)−H bonds of Phe derivatives 157a–v having installed the bidentate auxiliary, 2-(pyridine-2-yl)isopropylamine (PIP-amine) 158, was attempted using Selectfluor in the

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

• intermediate B through the C–H bond-activation process. Oxidative addition of the intermediate B with Selectfluor affords the palladium(IV) species C, followed by reductive elimination and ligand dissociation to give the final product. Similar to these publications in strategy and products, in the same year

• has been proposed. First, a bis(terpyridyl)Pd(II) complex B is oxidized by Selectfluor with turnover-limiting to obtain Pd(III) C and a Selectfluor radical cation. Then, a transfer of a F· radical from the Selectfluor radical cation to an aryl trifluoroborate occurs, forming the C−F bond and producing

• formed from A with Selectfluor or NFSI instead of an organometallic intermediate as usual. Then, the activated Pd(IV)–F electrophile B would be capable of electrophilic fluorination of weakly nucleophilic arenes. This unusual mechanism of catalysis may provide a new idea to the catalysis of C–H

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• cyclopropanols 91 with Selectfluor to construct β-fluorinated ketones 114 (Scheme 25). In Loh’s work, the Fe(III)- or Ag(I)-catalyzed oxidative ring-opening and fluorination of cyclopropanols 91 via radical rearrangement is disclosed. Notably, this reaction proceeds at room temperature and tolerates a diverse

• cyclopropanols 91 with Selectfluor under mild and simple conditions (Scheme 26) [106]. It is worth mentioning that a number of electronically and sterically diverse β-fluorinated carbonyl-containing compounds 114 and γ-fluoro alcohols 115 could be prepared through this method. In 2015, Duan and co-workers

• trifluoromethylation/trifluoromethylthiolation of cyclopropanols. Ag(I)-mediated oxidative ring-opening/fluorination of cyclopropanols with Selectfluor. Photocatalyzed ring-opening/fluorination of cyclopropanols with Selectfluor. Na2S2O8-promoted ring-opening/alkynylation of cyclopropanols with EBX. Ag(I)-catalyzed

Cobalt bis(acetylacetonate)–tert-butyl hydroperoxide–triethylsilane: a general reagent combination for the Markovnikov-selective hydrofunctionalization of alkenes by hydrogen atom transfer

• Xiaoshen Ma and
• Seth B. Herzon

Beilstein J. Org. Chem. 2018, 14, 2259–2265, doi:10.3762/bjoc.14.201

• reduction conditions, alkene 3a was transformed to isobutyl p-methoxybenzoate (4a) in 86% yield (entry 1, Table 1). Inspired by the methods of Boger [12] and Hiroya [13], a number of fluorination reagents were examined to achieve hydrofluorination. Although no product was observed using SelectFluor

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

• result was obtained by replacing PhI(OAc)2 with PhI. In addition, phosphates were suitable nucleophiles in this reaction, giving phosphoryloxylactones in good yields [44]. A similar catalytic cyclization of unsaturated amides leading to oxazolines and dihydrooxazines was developed, in which Selectfluor

• afford the diacetoxylation products in moderate yields and enantioselectivity when using Selectfluor as a terminal oxidant (Scheme 6). Diamination of alkenes The diamination of alkenes is attractive due to the significance of diamino moieties in diverse fields of the biomedicinal and pharmaceutical

• iodotoluene [27]. Based on this seminal work, Gilmour and co-workers reported a catalytic difluorination of alkenes using an inexpensive p-iodotoluene as the catalyst and Selectfluor as the terminal oxidant [63]. Terminal olefins proved to be viable substrates for this reaction. It is worth noting that the

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• fluorooxygenation of readily accessible N-allylcarboxamides via an I(I)/I(III) manifold to generate 2-oxazolines containing a fluoromethyl group. Catalysis is conditional on the oxidation competence of Selectfluor®, whilst HF serves as both a fluoride source and Brønsted acid activator. The C(sp3)–F bond of the

• enable this transformation [28][29]. Employing Selectfluor® as the terminal oxidant, it was possible to generate p-TolIF2 in situ from p-iodotoluene and an inexpensive HF source [30][31][32][33][34][35]. This strategy proved to be mild and general, smoothly converting terminal olefins to the

• DCE (0.2 mol·L−1) with 20 mol % catalyst loading, and using Selectfluor® as the oxidant. An initial reaction screen, based on the conditions reported for our vicinal difluorination study [9], began with an exploration of the effect of amine/HF ratio. This was deemed prudent due to the perceived

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• Selectfluor gave the corresponding (Z)-monofluoroalkenes 64 in good yields (Table 2). The reported results showed that the methodology was suitable to replace an amide bond and could be used in late-stage fluorination to access monofluoroalkene-based dipeptide isosteres. Xaa-ψ[CF=CH]-Xaa The preparation of

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• ), followed immediately by a fluorination reaction. However, this did not yield any of the desired vicinal difluorinated material. It is possible that alternative electrophilic fluorinating reagents such as Selectfluor [28] could give different results, but this was not investigated in this work. In a final

• . Accordingly, two piperidinedione substrates (21a and 21b) were prepared [32][33], containing a Boc or a benzyl protecting group, respectively (Scheme 2). Substrate 21a was first treated with Selectfluor in acetonitrile according to a mild protocol developed by Smith and co-workers for the α-fluorination of

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• methyl substituted difluoropyrazolone 12 in modest yield. Finally, an α-substituted β-ketoester was successfully converted to the pyrazolone before monofluorination using one equivalent of Selectfluor to prepare pyrazolone 13, also in moderate yield. In general the optimised approach seems to apply to a

• physical form in the one-pot two-step mechanochemical procedure. Optimised conditions for the one-pot synthesis. Substrate scope of the one-pot, 2 step mechanochemical synthesis (isolated yields). a1 equiv Selectfluor used. Optimisation of pyrazolone formation. Optimisation of pyrazolone fluorination

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• selectfluor [101][102]. They could control the selectivity of the reaction through LAG using ACN (≈10% v/v of total materials) to get predominantly mono-fluorinated product over difluorinated derivatives (Scheme 27). Contrastingly, addition of 1.0 equiv of Na2CO3 led to switching of the selectivity

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• ]. Rao and co-workers found that both biaryl ketone and aryl alkyl ketones could be regioselectively hydroxylated in satisfying yields. The reaction proceeded in TFA/TFAA in the presence of Pd(OAc)2 as catalyst and several type of oxidants including selectfluor, PhI(OAc)2 and K2S2O8, respectively (Scheme

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• a catalytic system consisting of (BPMED)CuI (copper(I) bisimine complex), N-hydroxyphthalimide (NHPI), KB(C6F5)4 and KI. The protocol allowed the selective fluorination of various substrates, including cycloalkanes and benzylic compounds using commercially available Selectfluor as fluorine source

Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH₄SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition

• A. Srinivas Reddy and
• Kenneth K. Laali

Beilstein J. Org. Chem. 2015, 11, 1641–1648, doi:10.3762/bjoc.11.180

• ionic liquids [BMIM][NTf2] and [BMIM][PF6] as solvent, in the presence and absence of Selectfluor. Comparative product analysis studies demonstrate that the ability of Selectflour to promote oxidative/electrophilic dihalogenation/dithiocyanation with TMSX/NH4SCN (as observed previously for 1-arylallenes

• additions in halofunctionalization with TMSX/Selectfluor and thiocyanation reactions with NH4SCN/Selectfluor. These competing pathways are influenced by the nature of the anion, allene structure, and the choice of solvent. Keywords: allene esters; oxidative electrophilic dihalogenation/conjugate addition

• ; Selectfluor; TMSX and NH4SCN; Introduction Whereas the synthetic potential of SelectfluorTM (F-TEDA-BF4) as an efficient, mild, and selective reagent for fluoro-functionalization of organic compounds is widely recognized and exploited [1][2][3][4][5][6][7][8][9][10], its ability to act as mediator or

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• bioactive natural products [6][7][8][9][10][11]. The synthesis of 3-substiuted 3-fluorooxindoles has been described in the presence of Selectfluor as a commercial source of F+, starting from 3-substituted indoles, in acetonitrile/water. These derivatives have been used as key adducts for the indole

• to C-3 fluorinated indole derivatives was less investigated. Fluorination of trialkylstannylindole derivatives with cesium fluoroxysulfate or Selectfluor was investigated for the synthesis of the corresponding 3-fluoroindoles [17]. A borane–tetrahydrofuran complex has been used to study the reduction

• was difluorinated highly regioselectively at the C-3 carbon site with Selectfluor [20]. The C-3 monofluorinated indole derivatives were supposed to serve as intermediates in the transformation and can be isolated under suitable reaction conditions [21]. We envisaged that the aminofluorination of the

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• ) redox couples could be accessed using external stoichiometric oxidants (i.e. Selectfluor or hypervalent iodine compounds) [73]. As schematically shown in Figure 1 this approach allows a double functionalization of simple alkenes with subsequent formation of new C–X and C–C bonds in a single catalytic

• first example of C–H functionalization by alkylgold intermediates. The optimized conditions required the use of the electrophilic complex [(p-CF3Ph)3PAuNTf2] and 30 equivalents of water, in order to increase the solubility of Selectfluor in THF. Heteroarylation of alkenes with arylboronic acids under

• the assistance of redox gold catalysis was also elegantly investigated by Toste’s group. In particular, aminoarylation of terminal olefins was documented in the presence of catalytic amounts of [dppm(AuBr)2] (3 mol %) and Selectfluor as the stoichiometric oxidant [78]. Despite the undoubted synthetic

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

• trifluoromethyl arenes without the use of trifluoromethylating reagents rely on an aryl CF2–F bond disconnection. A clever example of this strategy has been described by V. Gouverneur et al. starting from aryl difluoroacetic acids [117]. The latters can react with Selectfluor® and a catalytic amount of silver

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• electrophilic reaction with Selectfluor (F-TEDA-BF4, 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate)), as developed by Bank [7][8][9]. The Cahard [10][11][12] and Shibata [13][14] groups combined cinchona alkaloids and Selectfluor for asymmetric fluorination of substrates such as

• imido-protected phenylglycines (up to 94% ee), indanones and tetralones (up to 91% ee), ethyl α-cyanotolyl acetates (up to 87% ee), and cyclic β-ketoesters (up to 80% ee) [15]. A catalytic approach for the cinchona alkaloids and Selectfluor combinations has also been developed [16]. The Togni group

• employed chiral titanium Lewis acid TiCl2(TADDOLate) for the asymmetric fluorination of β-ketoesters (up to 96% ee) [17][18][19][20]. Most Selectfluor-promoted asymmetric fluorinations require a stoichiometric amount of chiral promoters to suppress the competitively direct achiral fluorination. Different

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by ¹⁹F NMR

• Michaela Braitsch,
• Hanspeter Kählig,
• Georg Kontaxis,
• Michael Fischer,
• Toshinari Kawada,
• Robert Konrat and
• Walther Schmid

Beilstein J. Org. Chem. 2012, 8, 448–455, doi:10.3762/bjoc.8.51

• glacial acetic acid (Scheme 1) [25]. Treatment of bromide 3 with Zn and N-methylimidazole [26] afforded the protected maltal derivative 4, which was transformed to the target compounds by utilizing Selectfluor® as a fluorinating agent [23][27][28] in a nitromethane solution. The mixture of anomeric 2

• relaxation filter. Syntheses of maltose derivatives; reagents and conditions: (a) Ac2O, Pyr, 97%; (b) HBr, AcOH, 99%; (c) Zn, N-methylimidazole, ethyl acetate, 74%; (d) Selectfluor®, CH3NO2, 40%; (e) NaOMe, MeOH, 99%; (f) NH2NH2·HOAc, DMF, 94%; (g) DAST, CH2Cl2, 89%; (h) NaOMe, MeOH, 99%; (i) α,α

Combination of gold catalysis and Selectfluor for the synthesis of fluorinated nitrogen heterocycles

• Antoine Simonneau,
• Pierre Garcia,
• Jean-Philippe Goddard,
• Virginie Mouriès-Mansuy,
• Max Malacria and
• Louis Fensterbank

Beilstein J. Org. Chem. 2011, 7, 1379–1386, doi:10.3762/bjoc.7.162

• the synthesis of 3-fluoro-2-methylene-pyrrolidine (3a) and -piperidine (3b) from 1,5- and 1,6-aminoalkynes, respectively, using a combination of a gold-catalyzed hydroamination reaction followed by electrophilic trapping of an intermediate cyclic enamine by Selectfluor. Careful attention was paid to

• the elucidation of the mechanism and Selectfluor was suggested to play the double role of promoting the oxidation of gold(I) to a gold(III) active species and also the electrophilic fluorination of the enamine intermediates. Keywords: cycloisomerization reactions; fluorinated pyrrolidines; gold

• catalysis; Selectfluor; Introduction The useful properties of fluorinated compounds in medicinal chemistry have motivated an intense effort towards the synthesis of new molecules bearing fluorine substituents [1][2]. Therefore, the development of a rapid access to C–F bonds is of great importance. Quite

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• (Scheme 53). The latter is the first example of a gold-catalyzed intramolecular C–C cross-coupling reaction involving aryl C–H functionalization with Selectfluor® as the oxidant. 2,4-Dien-6-ynecarboxylic acids 316 undergo gold-catalyzed tandem 1,6-cyclization/decarboxylation to afford 2,3-disubstituted