Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• ), and appetite suppressants (e.g., phentermine) [6]. Phenethylamines can be produced via numerous different procedures [7]. One of the oldest methods involves the reduction of benzyl cyanide with H2 in liquid ammonia with Raney-Nickel catalyst at 130 °C, and high pressure [8]. Another known method is

• ); 13C NMR (151 MHz, D2O) δ 122.41, 124.77, 129.01, 133.06; ESI-MS m/z: [M + 1]+ 171.0; found, 171.1; mp 190–191 °C. Benzyl alcohol (9b): The product formation was monitored by TLC using Hex/EtOAc (6:1). Once cooled to room temperature, the mixture was acidified with 20% HCl solution and extracted with

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• salts [34]. Under these conditions, N-benzyl-4-methylbenzenesulfinamide (6aa) was not observed, and N-benzyl-p-toluenesulfonamide (5aa) was isolated in 29% yield (Table 1, entry 4). To prevent the regeneration of tert-butyl 3-(p-tolylsulfinyl)propanoate (4a) and employ milder conditions, a study was

• primary amine-containing HIRs, or it might be due to the inability of the benzyl moiety to stabilize the sulfenate ion during the reaction. For tert-butyl 3-(p-tolylsulfinyl)propanoate (4a), and similarly to the outcome obtained for BBX 2a, sulfonamides 5ab and 5ac were obtained with moderate yields. The

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• in moderate yields (42–60%), high diastereoselectivities and good enantioselectivities (68–88% ee) (Scheme 6). The authors also attempted the reaction using N-benzyl-protected 3-chlorooxindole as a substrate. However, in this case, no reaction was observed, which indicated that the N–H group of the 3

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• benzyl azide and triethylgermanyl acetylene (see Supporting Information File 1). The most effective conditions were found to be based on the classical combination of CuSO4/NaAsc, with optimisation (see Supporting Information File 1) delivering the general conditions shown in Scheme 2. These afforded a

• and the starting material could be recovered in each case, consistent with observations by Lam and MacMillan [71][72]. Variation of the steric and electronic parameters of the germanyl acetylene was straightforward (14–17; Scheme 2b). Several limitations were observed (Scheme 2d): benzyl azides

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• a 4 mmol scale gave dimethyl ester 11a in 99% yield. Unexpectedly, the reaction of branched alcohols with diacyl chloride 2a failed. For example, the reaction with benzyl alcohol resulted in the formation of an overly complex mixture of products. Adding bases to trap HCl did not improve the

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• % yield, however, the related benzyl derived ylides gave 3i and 3j in 73% and 61% yields, respectively. Phenyl esters performed well with this methodology (3k,l), but switching to anilide-derived ylides were consistently poorer performing. The N-phenyl ylide derivative reacted to produce 3m in only 50

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• order to lead to the expected fluorinated tetrahydropyridazines (Figure 4). Results and Discussion First, the difluoro- and trifluoromethylated hydrazones 3a–f were synthesized by condensing the corresponding hydrazide with the fluorinated aldehyde hemiacetal 2a or 2b (Scheme 2). Benzyl and tert-butyl

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

• regeneration of 1-fluoro-3,3- dimethylbenziodoxole (12) in 91% yield from isolated benzyl alcohol after the fluorination reaction. A mechanism of the reaction was proposed (Scheme 13) in which the iodane-activated alkene is attacked by fluoride and the aromatic ring, to form a fluorinated phenonium

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• trifluoromethylthiolated organic peroxides 44 in good yields. Benzyl C(sp3)–H The direct α-functionalization of alkylaromatic compounds 45 with TBHP with the formation of the mixed peroxides 46 was firstly reported by Minisci using Gif conditions – Fe(NO3)3/HOAc/Py (Scheme 19) [61]. Notably, high yields of peroxides 46

• carried out without solvent and at room temperature, using copper(II) acetate as the catalyst. The reaction pathway of tert-butyl perbenzoate synthesis from benzyl nitriles 60 involves the formation of intermediate D. The Kornblum–DeLaMare rearrangement of peroxide D gives benzoyl cyanide E, which is

• further attacked by TBHP to give product 61. Benzyl alcohols 62 were also converted into tert-butyl perbenzoates 63 under the action of the TBAI/TBHP system (Scheme 22) [65][66]. During the process, TBHP oxidizes TBAI into iodine, which reacts with the second TBHP to generate tert-butylperoxy radical B

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• , see Scheme 1). In order to break the symmetry and to generate the acid function only on one side, benzyl protection was performed. From diols 1, 2, and 3 statistical mixtures of unprotected, mono-, and di-protected products were obtained, from which the isolation of the desired mono-protected products

• bicarbonate (NaHCO₃) provided acids 7, 8, and 9. A byproduct is obtained during oxidation and it is assumed that this is the molecule oxidized at the benzyl position (see Supporting Information File 1, compounds 35–40). Work-up and isolation proved to be difficult, and therefore, the acids were directly

• converted into the methyl esters 10 (54%), 11 (52%), and 12 (46%). The benzyl-protecting group was removed hydrogenolytically to give products 13 (85%), 14 (65%), and 15 (99%). The alcohols were then converted to the triflates 16 (28%), 17 (41%), and 18 (63%). We have chosen 3,4,5-trimethoxybenzaldehyde (19

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• was to be evidenced by a substitution reaction at the alpha position. We started testing the different bases with lithium bis(trimethylsilyl)amide [39]. The reactions did not take place in the presence of LiHMDS (Table 1, entries 1 and 2), using either benzyl bromide or methyl iodide as electrophiles

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• salt, subsequently leading to decarboxylative C–C coupling. Notably, this method achieves the incorporation of two fluorine atoms in the benzyl position without resorting to hazardous fluorination reagents, transition-metal catalysts, or organometallic compounds. The utility of this reaction is

• benzyl ester generated rather than the corresponding methyl esters. The reaction was also performed with a 6-membered cyclic diaryliodonium salt, which proceeded successfully and produced the respective iodo-containing arylated product in 59% yield with 76% ee after 24 h. Using the same reaction

• of O3-arylated galactosides 64 by reacting benzyl-protected galactoside 63 with diphenyliodonium triflates 16 at room temperature in the presence of potassium tert-butoxide as the base (Scheme 26) [77]. This transition-metal-free approach simplifies the synthesis process. Electron-pushing and

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• , albeit, in low yield (Scheme 19) [25]. Cleavage of the benzyl groups using boron tribromide afforded β-31a. In contrast to indirubin-N-rhamnoside 17a, its isomer β-31a proved to be rather unstable. This fact was already earlier observed for indigo-N-rhamnoside 5d and again suggests that compounds

• -glycosides Sassatelli et al. reported the synthesis of isoindigo-N-glycosides β-57a–c by reaction of benzyl-protected isatin-N-glycosides β-56a–c with oxindole (55) (Scheme 35) [53][54][55]. Deprotection by BBr3 afforded β-58a–c. Isatins 56 were prepared by glycosylation of indoline, benzylation, and

• oxidation with CrO3. Although this approach allowed for the synthesis of acceptor-substituted isatin-N-glycosides, it proved to be tedious and the yields were low. In a similar way, acetyl-protected isoindigo-N-glycosides were prepared. In addition, benzyl-protected isoindigo-N-glycoside β-58d, containing a

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• ]. In this context, while significant contributions have highlighted the reliable use of diverse organometallic species in the three-component coupling, most examples of sp3-hybridized compounds have remained restricted to allyl [5] or benzyl [5][6] organometallic reagents. Conversely, examples of

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• -benzyl-2-(4-methylphenyl)oxazole-4-carboxylate (5a) in 13% yield (Table 3, entry 1). Several conditions were considered, but the yield of 5a did not improve. On the other hand, the addition of two equivalents of water increased the yield, indicating the important role of a stoichiometric amount of water

• experiments were conducted in the same way. In the deuteration experiment, the reaction was quenched with deuterium oxide (0.2 mL) instead of acetic acid. The decrease of the integral of the signal of the benzyl proton was confirmed by 1H NMR analysis. Synthesis of polyfunctionalized methane derivatives

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• carried out without the presence of terminal alkyne, although no ee value was obtained. Therefore, they speculated that the direct substitution at the benzyl position is the key to causing the side reaction that affected the enantioselectivity. Recently, Zhu and Xu et al. [74] achieved the η-nucleophilic

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• a new family of isatin-based α-acetamide carboxamide oxindole hybrids using the versatile Ugi four-component reaction [18]. Sixteen hybrids were prepared by reacting 5-amino-1-benzyl-3,3-dimethoxyindolin-2-one, benzyl isocyanide, carboxylic acids, and aldehyde/ketone derivatives, catalyzed by ZnF2

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

• . Mechanistically, this transformation can be understood as follows: first, a Br/Cl/CF3 radical is formed via anodic oxidation, which subsequently attacks the olefin. The newly formed benzyl radical is oxidized to a carbocation, which undergoes nucleophilic attack by DMF. Hydrolysis of the imine delivers the final

• aliphatic alcohols, benzyl alcohols are also suitable reagents. Numerous LSF examples and upscaling were demonstrated. The mechanism involves two anodic oxidations: first, the thiophenol is oxidized at the anode, forming a sulfur radical that attacks the isocyanide. The newly formed carbon radical is then

• have been developed, the combination of electrochemistry with organocatalysis is generally less explored. In this context, Wang et al. combined organocatalysis and electrochemistry for the benzyl amination via C–H/N–H dehydrogenative cross-coupling of alkyl arenes with azoles [39]. According to the

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• ]. In contrast, the protocol reported herein provides 94–98% yield when employing longer chain-containing aldehydes (1c–e). In addition to resorcinol, 2-methylresorcinol is commonly used in resorcin[n]arene synthesis as radical oxidation of the methyl unit in the ArCH3 fragments provides a benzyl

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

• and pivalamide 7j were formed in trace quantities whereas the benzyl derivative 7k was isolable. The enamide 7l was not observed. Intriguingly, cyclopropyl and cyclohexyl derivatives 7m and 7n, respectively, were formed and isolated in moderate yields. Furyl derivative 7o was isolated in 63% yield

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• detection of benzaldehyde which was considered to be formed by the NaClO-mediated oxidation of benzyl alcohol generated by hydrolysis. Changing the oxidizing reagent to crystalline NaClO·5H2O nicely solved the problem with the realization of 86% isolated yield of 2b by the utilization of this oxidant (2

• the facile procedure presented here opens novel routes to the application of these intriguing products in a variety of fields. Experimental General procedure for the formation of the epoxyesters (GP-1): Benzyl (E)-2,3-epoxy-4,4,4-trifluorobutanoate (2b) GP-1A (by use of aqueous NaClO): To a solution

• C11H9F3O3: C, 53.67; H, 3.68; found: C, 53.54; H, 3.89. General procedure for the ring opening of epoxides (GP-2). Benzyl 2,3-anti-4,4,4-trifluoro-3-hydroxy-2-(p-methoxyphenyl)amino-butanoate (3ba) p-Anisidine (0.07 g, 0.60 mmol) was added to an EtOH (3 mL) solution of compound 2b (0.12 g, 0.50 mmol), and

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• it with our known iodonium species in the activation of Au(I)–Cl bonds. Results and Discussion As immediate precursor to the target structure 7Z, the literature-known isoxazole 10 was synthesized via a Cu(I)-catalyzed cycloaddition between (2-iodophenyl)acetylene (8) and benzyl nitrile oxide, which

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• dioxide; Introduction Electrochemical reduction of benzyl alcohol derivatives can induce reductive cleavage of a C(sp3)–O bond [1] at the benzylic position to generate the corresponding benzylic anion species. This protocol has been frequently applied to electrochemical carboxylation [2][3][4][5][6][7][8

• ][9][10][11], yielding phenylacetic acids. For example, Troupel et al. successfully performed electrochemical reduction of benzyl ethers and several esters such as acetate, trifluoroacetate, benzoate, and dibenzyl carbonate derived from benzyl alcohols, including 1-phenylethanol compounds, in the

• presence of carbon dioxide to give the corresponding phenylacetic acids [12]. We found that alkyl benzyl carbonates and benzal diacetates (benzylidene diacetates) were also applicable to electrochemical carboxylation with C(sp3)–O bond cleavage at the benzylic position, yielding phenylacetic acids [13] and

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• new methodology used bench-stable allyl-1,3,2-dioxaborinane (27) in the reaction with preformed crude N-aryl-, N-benzyl- and N-allylimines in the presence of 2–8 mol % of the relatively simple 3,3’-Ph2-BINOL catalyst 3 at 50 °C in a microwave reactor at 10 W irradiation for 1 hour to afford amines 26

• . Therefore, it was conducted under an inert atmosphere in anhydrous dichloromethane with 3 Å molecular sieves. Benzyl carbamates 48 showed excellent enantioselectivities (90–97%) and moderate to high yields (58–94%) across a wide range of allylation reagents 49 on a submillimolar scale, including 2

• , creating the desired syn-(2R,3S)-homoallylic amine 120 in high diastereo- and enantioselectivity. The reaction was tested with various aryl, benzyl, allyl, and alkyl-functionalised β-formyl N-morpholinyl amides 119; the amide function was also varied. Yields were scattered across the 31–90% range, with the

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• time of two days under a pressure of 0.8 GPa [23]. Less reactive benzyl malonates, which allow for the cleavage of a free carboxylic group without the need for harsh base- or acid-mediated conditions [24], undergo additions catalyzed by primary amines [19]. However, these transformations are hampered

• low conversions and stereoselectivities when applied to benzylidene acetones or cyclic enones (vide infra). In our latest research in establishing a mild organocatalytic protocol for incorporating benzyl malonates and bisthiomalonates into cyclic enones and benzylidene acetones, we have developed a