Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• , TFA, and trichloroacetic acid) and even weak acids (e.g., HF, Et3N·3HF, and AcOH) react with iodonium ylides to give formal X–H insertions [127][128][129][130]. In 2022, Murphy et al. disclosed a computational and experimental investigation into the reaction scope and the mechanism by which such X–H

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• approach using Et3N·3HF as an alternative to the DAST reagent. We controlled the stereochemistry of the nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-4-O-triflate-β-ᴅ-talopyranose using Et3N·3HF or in situ generated Et3N·1HF. The influence of the fluorine atom at C2 on reactivity

• at C4 could contribute to a new fluorine effect in nucleophilic substitution. Finally, with the continuous objective of synthesizing novel multi-vicinal fluorosugars, we prepared one difluorinated and one trifluorinated alditol analogue. Keywords: deoxyfluorination; Et3N·3HF; fluorine effect

• various deoxyfluorination reaction conditions. In our specific case, we were able to modulate the stereoselectivity of the nucleophilic fluorination at C4 with the use of Et3N·3HF. As proposed by the group of Linclau [20], we support the involvement of an oxiranium intermediate (results reinforced by

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• sources (e.g., Et3N⋅3HF and HF–pyridine) and halonium ion sources (e.g., N-halosuccinimides) are relatively cheap and easily available, halofluorination might be an economic way to obtain vicinal halofluorides that can be transformed further in various ways thanks to the different leaving group abilities

• (rac)-30 was determined using NOESY analysis. From the diester 4, however, a mixture of two fluoroselenides was formed, and the separation failed. The use of PhSeBr/Et3N⋅3HF for the fluoroselenation – another reagent combination that was previously unknown in the literature – gave similar results

• products and subsequent cyclization into fused-ring cyclopropanes. Two new fluoroselenation protocols using PhSeBr/Deoxo-Fluor® and PhSeBr/Et3N⋅3HF, respectively, have been described, but the substrate scope of this reaction was more limited. The transformation of the obtained fluoroselenides into allyl

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

• formation of fluorinated products with an overall retention of the stereochemical configuration suggests a mechanism wherein a palladium-π-allyl intermediate undergoes a rapid π-σ-π isomerization. In 2013, the first example of an allylic C–H fluorination reaction of simple alkenes with Et3N·3HF as a

• achieved using Et3N·3HF as the fluorine source with a high catalyst loading (20–30 mol %) affording the products in 45–92% yield [70]. The heteroatom-containing functional group (R1) is necessary for good reactivity and regioselectivity. α-Fluorination of acidic carbonyl compounds: In 2011, Shibatomi and

• Scheme 45a. Cyclooctadiene iridium chloride dimer, [IrCl(COD)]2, was an effective catalyst to promote this fluorination with Et3N·3HF, forming allylic fluorides in moderate to good yields. This facile method shows a good regioselectivity to gain the branched isomer within 1 h. Later in 2017, they

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

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

• optimal amine/HF ratio (1:4.5) is easily obtained by combining commercially available triethylamine tris(hydrogenfluoride) (Et3N·3HF) and Olah’s reagent (Pyr·HF). Broad functional group tolerance is observed in the products, the structures of which display the stereoelectronic fluorine gauche effect

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• fluorination of sulfides having various EWGs at their α-position using Et3N·3HF [9][10]. Since then, we have systematically studied the electrochemical fluorination of numerous organic compounds, heterocycles, and macromolecules by using various fluoride salts such as Et3N·nHF (n = 3–5) and Et4NF·nHF (n = 3–5

• ) [11][12][13][14][15][16][17][18][19]. On the other hand, Simonet and co-workers reported the anodic fluorination of alkyl phenyl sulfides having an EWG on the phenyl group in Et3N·3HF/MeCN to provide α-monofluorinated products in moderate yields [20]. We also achieved the anodic fluorination of benzyl

• , entry 1). In this case, the starting 1a was consumed completely at 4.5 F/mol. It is well known that the fluoride salt, Et3N·3HF is easily oxidized (2.0 V vs Ag/Ag+) because it contains a considerable amount of free Et3N [25]. However, the fluorination proceeded well particularly in a CH2Cl2 solution

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• with Et3N·3HF proceeds with excellent diastereoselectivity [19]. Et3N·3HF is less acidic than Olah’s reagent, disfavouring SN1 and rearrangement pathways [20][21]. Indeed, the use of this reagent for the epoxide opening of cis-2 led to (±)-syn-3 in excellent yield (Scheme 2), with no significant

• alkene was cis-configured, its introduction was possible from the start (Scheme 3). Hence, following literature procedures [24][25][26], the reaction of cis-1 with 2,2-dimethoxypropane and subsequent epoxidation led to 7. However, epoxide opening with Et3N·3HF was accompanied by acetonide rearrangement

• purification was required, which was convenient on scale. The reaction of (±)-trans-2 with neat Et3N·3HF at 120 °C for 16 h led, after aqueous work-up, to (±)-anti-3 in high diastereomeric purity (see Supporting Information File 1). The 19F shift of −195.3 ppm is different compared to that of (±)-syn-3 (−204.4

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

• Et3N·3HF according to O’Hagan’s method [34] (Scheme 3). This did effect epoxide-opening to some extent, but the reaction was rather unsatisfactory because it was low-yielding and non-regioselective, which made full characterisation of the product mixture (32/33) impossible. Nevertheless, an analytical

• it was found that the inclusion of the additive TMS-morpholine [36][37] was also required to ensure a high diastereoisomeric excess of 38a. The epoxide 38a was then ring-opened using Et3N·3HF to deliver the difluorodiol 39a as a mixture of regioisomers. This mixture subsequently converged during the

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• % yield), however, diepoxides 8b and 8c (35%) could not be separated, and therefore were taken as a mixture of isomers to the next step in the reaction sequence. Treatment of 8a with Et3N·3HF at 140 °C resulted in its full conversion to the hydrofluorinated ring-opened diol 9a as a single regioisomer, a

• with Et3N·3HF at 120 °C generated the tetrafluorocyclohexane 11a, the structure of which was confirmed by X-ray crystallography (Scheme 2). Although the conversion of 10a to 11a was high as judged by 19F NMR, the isolated yield was modest as the compound was volatile and sublimed easily under reduced

• then applied to diastereoisomers 8b and 8c as illustrated in Scheme 3. Fluorination of the isomer mixture 8b/8c with Et3N·3HF at 140 °C gave 9b and the racemic 9c as an inseparable mixture. Triflation of this product mixture generated 10b and 10c, isomeric products which could now be separated by

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• -withdrawing effect of a substituent greatly affects the electron-transfer step from the substrate to the anode. At first, anodic fluorination of ethyl α,α-bis(phenylthio)acetate (1b) [30][31] was carried out at platinum plate electrodes in an undivided cell using various solvents in the presence of Et3N·3HF

• formation of only one byproduct. Next, anodic fluorination of 1b was carried out in MeCN using various poly(HF) salts until the substrate was completely consumed and the results are shown in Figure 1. As mentioned earlier, the anodic fluorination of 1b using Et3N·3HF provided α-fluorinated product 2b

• case of α,α-bis(phenylthio)acetone (1d) [32], the use of Et3N·3HF and Et4NF·3HF resulted in predominant α-fluorination to provide the corresponding monofluorinated product 2d in good to moderate yields (Table 3, entries 1 and 3). On the contrary, when higher HF content salts such as Et3N·5HF and Et4NF

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• method for the synthesis of oxindoles and 3-oxotetrahydroisoquinolines 47 via intramolecular cyclization under C–C-bond formation was reported by Atobe, Fuchigami et al. (Scheme 18) [63]. The protocol is based on the anodic oxidation of α-(phenylthio)acetamides 46 in the presence of Et3N∙3HF. The latter

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• [56][57]. Manfredini et al. have shown that selective deprotection of the TBDMS groups in the presence of a t-Boc protecting group is possible when using Et3N·3HF [58] and also in our case using Et3N·3HF in THF resulted in product 4 with good purity and yield (72%) [59]. Dimethoxytritylation could be

• min (79%); b) Et3N·3HF, Et3N, THF, rt, overnight (72%); c) DMTr-Cl, pyridine, 0 °C, 7 h (52%). Reagents and conditions: a) Et3N, Pd(PPh3)4, THF, CO (4 bar), 48 h, 70 °C (68%); b) Et3N·3HF, Et3N, THF, overnight, rt (86%); c) DMTr-Cl, pyridine, DCM, overnight, rt (82%). Reagents and conditions: a) Et3N

• , Pd(PPh3)4, THF, CO (4 bar), 48 h, 70 °C (90%); b) Et3N·3HF, Et3N, THF, overnight, rt (43%); c) DMTr-Cl, pyridine, DCM, overnight, rt (9%). Supporting Information Supporting Information File 634: Experimental procedures, characterization data, and 1H and 13C NMR spectra of new compounds

The preferred conformation of erythro- and threo-1,2-difluorocyclododecanes

• Yi Wang,
• Peer Kirsch,
• Tomas Lebl,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2012, 8, 1271–1278, doi:10.3762/bjoc.8.143

• . Experimental Preparation of 7a and 7b: Commercially available 1,2-epoxycyclododecane (6) (5 mmol, 0.91 g, 9:1 trans/cis) and Et3N·3HF (4.0 g, 25 mmol) was added to a Teflon-coated reactor and stirred at 160 °C for 24 h. After cooling down, the reaction mixture was quenched with sat. NaHCO3 solution (50 mL) and