Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• described an elegant aryl–aryl cross-coupling procedure suppressing the formation of Grignard homocoupling byproducts relying on the use of FeF3 as catalyst, associated with strong N-heterocyclic carbenes (NHCs) and a source of fluoride anions [28]. A similar procedure involving sodium alkoxide additives

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• the electron-donating phenyl ring enabled the coordination of the alkyne with the Au+ complex in the α-position, which promoted the silyl ether to attack the β-position of the alkyne to promote a 6-endo-dig cyclization. Next, compound 11 was subjected to a solution of tetrabutylammonium fluoride (TBAF

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• 206.6, 154.9, 85.1, 82.3, 59.0, 45.0, 36.5, 32.2, 28.4, 18.1, 12.1 ppm; HRMS (m/z): [M + Na]+ calcd 424.2490; found, 424.2480; [α]D20 +37.4 (c 0.5, CH2Cl2). (5S,6R)-5-Ethyl-6-ethynyl-5,6-dihydro-2H-pyran-2-one (21): Caesium fluoride (290 mg, 1.91 mmol, 1.3 equiv) was added to a solution of the lactone

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• , temperature) [32], and introduces various effects of microwaves [33], cyclodextrines [34], or tetrabutylammonium fluoride on the N7/N9-product ratio [35]. It is therefore of interest to collect complementary data on analogous acylation reactions, which are required for a future comparative study. Intrinsic

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• approaches were contemplated for this purpose. Activation by alkoxides of the C3–SiEt3 or C3–SiMe2t-Bu bonds was ineffective. Conversely, treatment of the C3-benzyldimethylsilyl-appended derivatives with tetrabutylammonium fluoride led to cyclic siloxanes, which revealed to be competent donors for copper

• -catalyzed arylation reactions (Scheme 7). Fluoride-promoted arylation reactions of benzyldimethyl(alkenyl)silanes have been reported, and it is established that they proceed through the cleavage of the benzyl moiety from the benzyldimethylsilyl groups, leading to either dimethylsilanols or cyclic siloxanes

• activation by alkoxides did not prove useful, C3–Si bond functionalization is achieved from benzyldimethylsilyl units upon siloxane formation in the presence of TBAF. Protocols for fluoride-promoted Pd/Cu-catalyzed arylation, as well as Cu-catalyzed allylation and methylation, have been developed. Overall

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• ][29][30]. For example, Han and co-workers successfully developed a tetrabutylammonium fluoride-catalyzed cycloaddition of phenacylmalononitriles and nitroolefins for the diastereoselective synthesis of multifunctionalized cyclopent-2-ene-1-carboxamides [31] (reaction 1 in Scheme 1). Liu and Ban

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• and a carbon-filled polyvinylidene fluoride (C/PVDF) plate as anode. BMImBF4 0.1 M in acetonitrile was the catholyte, while the anolyte was a solution of tetraethylammonium tetrafluoroborate (Et4NBF4) in acetonitrile; after only 12 minutes of electrolysis the current flow stopped. Moreover, a

• carbon-filled polyvinylidene fluoride (C/PVDF) and the cathode material is described in Table 1. Electrolyzes were carried out at room temperature, under nitrogen atmosphere, using a solution of 0.1 M of BMImBF4 in acetonitrile as catholyte. Anolyte solution is given in Table 1. Electrolyte solutions

• cell. Anolyte (20 mL) and catholyte (20 mL) were separated through a Nafion® 438 membrane. The anode material was carbon-filled polyvinylidene fluoride C/PVDF and stainless steel for the cathode material. Electrolyzes were carried out at room temperature, under nitrogen atmosphere, using a solution 0.1

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

• olefins in moderate yields [5]. Prakash et al. also achieved fluoride-induced nucleophilic (phenylthio)difluoromethylation of carbonyl compounds using PhSCF2SiMe3 [6]. Quite recently, Shen et al., developed various nucleophilic, electrophilic, and radical difluoromethylthiolating reagents [1]. However

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• , while other synthetic approaches were explored to obtain these reagents, the SN2 strategy described in this work was the most efficient. Such synthetic alternatives included: first, a sulfur(VI) fluoride exchange (SuFEx) between perfluoroalkylsulfonyl fluorides and the corresponding silyl enol ether

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• developed based on other oxidizing agents, such as cobalt(III) fluoride [85], phenyliodine(III) bis(trifluoroacetate) (PIFA) [86] and tert-butyl hydroperoxide [87] (Table 3). In 1999, Tomatsu and co-workers performed the synthesis of menadione (10) through demethylation of 2-methyl-1,4-dimethoxynaphthalene

• (19), using cobalt(III) fluoride as oxidizing agent (Table 3, entry 1) [85]. The obtained results showed that the cobalt(III) fluoride catalyst was comparable with other oxidizing agents already well-established for this synthesis, like silver(II) oxide and ammonium cerium(IV) nitrate. Cobalt(III

• ) fluoride proved to be a good oxidizing agent for the synthesis of menadione (10). This approach furnished 10 in 92% yield, although the reaction required a longer reaction time compared to the few minutes using AgO and CAN. Another problem associated with the use of oxidizing metallic agents is the

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

• distinctive peak at 65.8 ppm in the 19F NMR spectrum (Scheme 3g), which was assigned to phenylsulfonyl fluoride (PhSO2F) [35], a byproduct often obtained in reactions with NFSI [36][37]. Trying to improve the rheology of the reaction mixture and to increase the basicity of the medium, we milled 3a and NFSI in

• reactivity of pyridine derivatives with NFSI, which are known to generate phenylsulfonyl fluoride via a transient generation of N-sulfonylpyridinium salts [37]. Analysis by 19F NMR spectroscopy of the crude reaction mixture of 3b and NFSI revealed the presence of PhSO2F (Scheme 3d), thus confirming the

• capacity of the nitrogen with the lone electron pair in 3b, and probably in 3a, to react with NFSI at the sulfonyl group to facilitate the formation of phenylsulfonyl fluoride (Scheme 3c). Other imidazole derivatives such as 2-methylimidazole (3c) and benzimidazole (3d) also underwent sulfonylation

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• and Scott showed [9] that in 50% acetone/50% water at 0.5 °C, a hydroxide ion was about 106 times more reactive than a water molecule towards benzenesulfonyl chloride. Also, for the same solvent, at 25.0 °C, they found [10] that the fluoride, with a considerably stronger carbon–halogen bond, reacted

• at least four orders of magnitude slower than the chloride as regards the solvolytic replacement of the halogen present in the benzenesulfonyl halide. For the reactions of the fluoride in 20% dioxane at 91 °C, the m-nitro derivative was shown to be subject to a strong nucleophilic catalysis by

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• Pd source together with the water-soluble Buchwald ligand sulfonated SPhos (sSPhos) and potassium fluoride as a base. The reaction was performed in a solvent mixture of dimethoxyethane, ethanol and water (DME/EtOH/H2O 9:9:2) at 120 °C under microwave irradiation for 30 min (Scheme 1) [78]. The

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• products in appreciable yield. Alkenyl fluoride, chloride, and bromide substrates 51/52 were found to be amenable to the reaction although with varying degrees of success, likely due to the competing base-promoted 1,2-elimination. With the cyclopropylidene-functionalized substrates 50a, ring-cleavage led

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• could have been due to an in situ chelation process. The level of selectivity was determined by HPLC to be >300:1 in favor of the β-configured cis-isomers (racemic mixture of 80a and 80b) [30]. Further, the desilylation using tetrabutylammonium fluoride (TBAF) gave racemic (±)-BCH-189 (1c). Chu et al

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• intramolecular nucleophilic attack by azide and the following deprotonation by a fluoride anion provide the final product 8 (Scheme 5). The derivatization of sulfonated aminonicotinates 8 could easily be achieved. Desulfonylation of aminonicotinate 8b proceeded smoothly in the presence of triflic acid (2.0 equiv

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• ester 56 was achieved through reaction of 55 with the pre-activated acid 17 with N,N’-diisopropylcarbodiimide (DIC) and DMAP. Removal of the TBS protection with a fluoride source and succeeding Mitsunobu inversion with 3-butenoic acid (37) went smoothly to give ester 57. This intermediate accommodated

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• between the catalyst and the substrate, which exclusively stabilize the transition state that forms the major enantiomer. Furthermore, Gouverneur and co-workers established an enantioselective nucleophilic fluorination protocol using a chiral bis-urea catalyst 41 and CsF as an inorganic fluoride source

• (Scheme 9a) [18]. By employing in situ-generated meso-episulfonium ions, they were able to synthesize β-fluorosulfides 39 in high yields up to 98% and enantioselectivities up to 94% ee. The key step in this transformation is the formation of the noncovalent catalyst–fluoride complex III during the phase

• -transfer step. This provides low amounts of reactive, nucleophilic fluoride in the nonpolar solution, circumventing thereby selectivity and reactivity issues owing to the high basicity of alkali metal fluorides [58][59][60][61][62]. By modifying the reaction conditions, the same group was also able to

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• (LG, e.g., phosphate, fluoride, nucleotide) are polymerized by the enzyme to form the desired polysaccharide (Figure 1A). Several classes of enzymes are available, including hydrolases, phosphorylases, sucrases, glycosyltransferases, and glycosynthases [19][20][21][22]. An excellent overview of the

• polymerization of cellobiose fluoride 1 was achieved using a cellulase produced from Trichoderma viride (Scheme 1A). The DP of the acetylated product was shown to be at least 22. Using a purified version of this enzyme, it was possible to obtain a synthetic analogue of Cellulose I [64]. A rough control of DPs

• produced polysaccharides with controlled substitution, but no control over the length [107]. Similarly, XG fragments prepared by enzymatic degradation of XGs were converted to the fluoride donors and used in the subsequent glycosynthase-catalyzed transformations. (XXXG)3, (XLLG)3, and XXXG-GGGG-XXXG were

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

• agents are essential for the wide-spread advancement of organofluorine chemistry to non-specialist chemists. Alternatives to F2, such as perchloryl fluoride (FClO3) [10] and the O-F reagents such as CF3OF [11], CF2(OF)2 [11], CsOSO2OF [12], CF3COOF [13], and CH3COOF [14] have been used as fluorinating

• useful electrophilic or radical fluorinating agents by virtue of their easy handling, efficiency, and selectivity. These non-hygroscopic nature and stability make them easier to handle than nucleophilic fluoride reagents. Potassium fluoride (KF) and naked fluoride anion salts are extremely sensitive to

• fluorination of pyridine or 2-fluoropyridine in anhydrous hydrogen fluoride [17][18] (Scheme 2). Not surprisingly, 1-1 did not become a popular reagent. In 1967, Banks et al. reported reactions of 1-1 with piperidine and triphenylphosphine, -arsine, and -stibine (Scheme 3, entries 1 and 2) [19]. The former

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• . Initially, resting Mn(TMP)F undergoes oxidation, generating oxomanganese(V) complex O=Mn(TMP)F (5A), followed by H-abstraction of the substrate 1 or 3, providing HO–Mn(TMP)F (5B) and a C-centered radical. The trans-difluoro-substituted Mn(TMP) intermediate 5C, generated by an excess of the fluoride source

• radioisotope for positron emission tomography (PET) in clinical and preclinical research is 18F. Radiopharmaceuticals should be prepared at the late stage of the entire synthetic protocol because of the short half-lives of radioisotopes [26][27][28][29]. In their study, the authors used an aqueous 18F-fluoride

• solution obtained by the nuclear reaction using a cyclotron, and manganese–salen complex 7 was used as a fluoride transfer catalyst, which facilitated late-stage C–H radiofluorination, affording the corresponding radiofluorinated bioactive molecules 8a–h. In general, the regioselectivity of fluorination

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• -isobutyrylguanine, N-benzoylcytosine, 6-O-allylhypoxanthine or N,N-dibenzoyldiaminopurine in 53 to 83% yield. The desilylation of the nucleosides 3a–f with tetrabutylammonium fluoride in tetrahydrofuran (THF) led to the formation of six different double-headed nucleosides 4a–f (Scheme 1) [38][39]. The synthesized

• (Scheme 17) [54]. The tert-butyldimethylsilyl-protected (TBDMS) nucleoside 76 was first hydrolyzed using NaOH, which was followed by TBDMS deprotection using tetra-n-butylammonium fluoride (TBAF) in tetrahydrofuran (THF) to afford the double-headed nucleoside 77. The TBDMS-protected nucleoside 73 was

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• covalently bind Lewis basic fluoride ions in a relatively stable fluorosulfite anion (FSO2−). Herein we report the application of liquid SO2 as a promoting solvent for glycosylation with glycosyl fluorides without any external additive. By using various temperature regimes, the method is applied for both

• equilibrium. Keywords: fluorosulfite; glycosyl fluoride; Lewis acid; liquid sulfur dioxide; metal-free glycosylation; Introduction The glycosylation reaction is still one of the most important and basic synthetic strategies in carbohydrate chemistry that provides access to the various types of

• –base (HSAB) theory the fluoride leaving group is considered to be a hard Lewis base [12][13]. Consequently, a series of fluoride-activating systems containing hard Lewis acidic centers have been published following the first report [7][14][15][16][17]. Among these promoters Sn(II) species (SnCl2–AgX, X

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• alkoxycarbenium ion intermediate 282, which is followed by a sequential cyclization to form secondary carbocation 283, which in the presence of fluoride ions affords 284, as shown in Scheme 66. Banerjee et al. explored the reactivity of cyclopropane carbaldehydes 285 with 3-butyn-1-ol in the presence of TiX4 for