An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• funnel over a 2–4 hour period, depending on the substrate, and is then left to react for an additional 1–3.5 hours to reach complete conversion of the substrate into the respective phosphonic ester. In this way, the dibromide substrate is always the limiting reagent, promoting full conversion to the

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• electrode on for 90 s and then off for 180 s. This was done to tune the rate of Cu(I) generation to match the rate of Cu(I) oxidation in solution and in so doing optimize confinement of the Cu(I) catalyst to the selected electrodes. Longer "on-times" would lead to more reagent generation making it harder

• for the confinement strategy to keep up. The result is a loss in confinement. It is important to point out that the reaction shown in Scheme 1 is not a typical electrosynthetic reaction. The cross-coupling reaction shown is a Cu(I)-catalyzed transformation that requires no recycling of a reagent

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• reagents, solvents, thioamides, and reagent ratios, are summarized in Table 1. We first performed the reaction of 1a (0.5 mmol) with N-phenylbenzothioamide (2a, 1.0 mmol) using organobismuth or organoantimony reagents 6 or 7 (1.0 mmol) in 1,2-dichloroethane (DCE) under aerobic conditions at 60 °C for 18 h

• reagent did not catalyze it (entry 17). The addition of triethylamine as the base afforded 8a in a low yield (32%) (entry 18). At room temperature, the reaction hardly proceeded (entry 19). Screening various thioamides (2a–5) showed different behavior in the reaction with 1a and 6a; 2a afforded the

• reacted in the presence of 6a in 1,2-DCE at 60 °C under aerobic conditions. The optimal reagent, Ph3BiCl2 (6a), can be easily and inexpensively synthesized on a 10 g scale by scaling up the reported procedure (see Supporting Information File 1) [36][37]. To investigate the efficiency and generality of the

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• based on silver either gave a complex mixture or unreacted starting material. Phosphonate 8 was converted into the corresponding thiophosphonate 9 in moderate yield using Lawesson's reagent. Cleavage of the methyl ester was easily accomplished in quantitative yield, producing racemic tryptophol CPA 1

• alternative [37] to Lawesson's reagent did not solve the problem. This prompted our search for alternative methodologies for the synthesis of thiophosphorus acids [38], particularly using the Stec reaction [39][40]. This work also led to the synthesis of CPA 3 [38]. Alternatives to the Stec reaction to

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• related to biological functions of ApppI. Results and Discussion The synthesis of the target compound ApppI(d2) started with commercially available 3-methylbut-3-en-1-ol (1), which was first oxidized to 3-methylbut-3-enoic acid (2) using freshly prepared Jones reagent as oxidizing agent. 3-Methylbut-3

• , 576.0631; found, 576.0630. All NMR data were comparable to those reported elsewhere for conventional ApppI [19][21]. Preparation of Jones reagent: CrO3 (25 g) was slowly and carefully added to conc H2SO4 (25 mL) with stirring. After complete addition, the formed mixture was further added in very small

• portions to ice-cold water (75 mL) with vigorous stirring to form the final Jones reagent. Synthesis of 3-methylbut-3-enoic acid (2) [27]: 3-Methylbut-3-en-1-ol (1, 3.0 mL, 2.56 g, 0.030 mol) was dissolved in acetone (150 mL), and the reaction mixture was cooled to 0–3 °C. Then, Jones reagent (15.6 mL) was

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• (Scheme 1b). Similarly, in the absence of metal catalysts, N-fluorobenzenesulfonimide (NFSI) was found to act as a mild fluorinating reagent for activated aromatics by mechanochemistry [5]. Such a collective effort to access halogenated substrates is understandable, owning the synthetic value of organic

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• cytotoxicity of the test compounds before the nitric oxide (NO) production assay. NO production in each well was assessed by measuring the accumulation of nitrite in the culture supernatants using Griess reagent. After 5 min of incubation, the absorbance was measured using a microplate reader (Thermo, Bio-rad

Synthesis of meso-pyrrole-substituted corroles by condensation of 1,9-diformyldipyrromethanes with pyrrole

• Baris Temelli and
• Pinar Kapci

Beilstein J. Org. Chem. 2022, 18, 1403–1409, doi:10.3762/bjoc.18.145

• the bilane intermediate by using DDQ (Scheme 2). Pyrrole was used as both reagent and solvent in these reactions. The desired product was not observed in the reaction medium when various catalysts (TFA, I2, AlCl3, InCl3, FeCl3, H2SO4, p-TsOH, Mont. KSF, Mont. K-10, and AgOTf) were used at different

• production of mono pyrrole metal-free corrole compounds and the polymerization reactions of the obtained compounds are ongoing in our laboratory. Experimental General information All reactions were performed under N2 atmosphere. All reagents and solvents were of reagent grade. The NMR spectra were recorded

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

• , we have shown that the Wightman reagent 6, a chiral chloronitroso derivative [27], led to a complete regio- and stereoselective reaction with functionalized dienes (Scheme 1). The chiral auxiliary contributes to both regioselectivity and stereoselectivity. After hydrolysis of the chiral auxiliary and

• we wondered whether it was possible to perform the whole synthetic sequence with this protecting group. Accordingly, the enol phosphate 13 was synthesized in five steps (26% overall yield) from 1,4-butanediol (Scheme 5). Since cycloaddition with the Wightman reagent 6 releases hydrogen chloride in

• obtained when using equimolar amounts of both 19 and 11b (Table 1, entries 1 and 2). These disappointing results with alkyne 19 prompted us to investigate the coupling with an organometallic reagent derived from vinyl iodide 20. This reagent was already synthesized and coupled with acyclic ketones in

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• available (H3B·SMe2, [H-B-9-BBN]2, H3B·THF) and prepared borane catalysts (dicyclohexylborane) in the hydroboration of heptanenitrile with HBpin as the turnover reagent (see Supporting Information File 1 for details). All boranes were catalytically active, with H3B·SMe2 displaying the highest activity. As

• adjusted to maximise efficiency for yield or chemoselectivity. Reaction of the turnover reagent, HBpin, in the absence of catalyst gave no observable reduction (see Supporting Information File 1). The optimised conditions were applied to a substrate scope, where the hydroboration products were converted in

• due to dehydrocoupling of the turnover reagent, HBpin, with the amine [39]. A range of nitriles containing functional groups were tested in catalysis to investigate the chemoselectivity of the reaction. Several reducible functionalities were tolerated by the catalytic protocol, including ester (1q, 48

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

• appropriate C3-silylated furfural [15] and dissolved in freshly distilled THF (0.2 M solution). The solution was cooled to 0 °C, and then the Grignard reagent (1.3 equiv in Et2O) was added dropwise (the rate of addition was equal to, or lower than 0.125 mL/min). The mixture was allowed to stir at 0 °C for 1 h

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• chemical potential [23]. The reactivities of two substrates A and B with the same reagent C can be compared on the basis of the relative values of ∆μAC and ∆μBC; the greater the value of ∆µ is, the faster will be the reaction. In this context, it may be noted that except for compound 6Aa, i.e., the

• reactivities towards the DA reaction with 1,3-butadiene, i.e., they are expected to undergo the DA reaction without the aid of a catalyst. Frontier molecular orbital (FMO) treatment of the DA reaction The FMOs of a molecule are very important parameters to reveal its reactivity towards a reagent [28]. In the

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• -Ts-Im), a cheap and commercially available reagent directly prepared from p-toluensulfonic acid by reaction with 1,1′-carbonyldiimidazole (CDI). The compound proved very effective for dehydrating oximes under mechanochemical acidic Beckmann conditions [44]. Moreover, it represents a suitable and

• -Tosylimidazole releases imidazole as a byproduct during the process. Therefore, we wondered whether imidazole could promote the formation of the target formamide 2. Imidazole, compared to p-tosylimidazole, is a cheaper reagent and makes the final purification process easier. As a matter of fact, by reacting 1.0

• intermediate was not detected by NMR or GC–MS analysis, possibly due to its instability [64]. Several studies carried out on our reaction crude at different times did not show the presence of compounds traceable to formylimidazole. The imidazole plays a dual role as promoting reagent and solid grinding

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• reagent, which allows to reduce the reagent waste to a minimum. Obviously, as this characteristic matches well with the increasing demands to realize a sustainable society. In electro-organic synthesis, electrode materials are one of the most significant parameters because reactions occur at the anode and

• a sustainable, scalable, and cost-efficient protocol; a specific catalyst is not required, and reagent waste can be avoided. In addition, the present work offers new perspectives for an electrosynthetic strategy toward oxidation reactions of aromatic alkyls. Experimental General protocol for electro

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• derivative 7 in acidic media, the latter playing the role of nucleophilic reagent which attacks to iminium salt 6 to give intermediate 8. Subsequently, intramolecular nucleophilic attack of the amino moiety to the carboxylate group in the intermediate 8 leads to the formation of the target products 4a–c

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• chain pathway can be involved, where an electron acts as a catalyst rather than a reagent [12][13][14][15][16][17][18]. In this reaction format, trans-anethole is an electron-rich dienophile and has widely been studied as a benchmark for single-electron transfer using photochemical and electrochemical

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• -halosuccinimides as the reagent. In the protocol, PEG-400 was used as an LAG agent and the reactions were conducted in an automated grinder in open-air at room temperature for quick access to halogenated derivatives. A wide range of substrates was compatible with NXS (X = Br, I, Cl) for electrophilic aryl

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

• 1,3-diketones [21], etc. Electrosynthesis is considered as a more sustainable approach to perform chemical reactions, and an interesting alternative to conventional synthetic methods both in laboratory and industry processes. In fact, the electron may be considered to be a clean reagent, which

• electrochemistry, NHC instability (and anodic electroactivity) prevented its cathodic generation and subsequent use as catalyst or reagent. Instead, the NHC was generated by chemical deprotonation using a strong base (DBU) and then applied in anodic esterification [30][31][32], and amidation of aromatic aldehydes

• [33]. Flow electrochemistry was applied to oxidize the Breslow intermediate to the corresponding electrophilic acylthiazolium intermediate, which then functioned as an acyl-transfer reagent, reacting with alcohols or amines. To the best of our knowledge, only one research group reported the cathodic

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• also explain why a yield increase is observed whenever the glyoxals or the α-aminoamides are used in excess. In each case the reagent in excess would react more quickly to “capture” proportionally more of its partner and diminish the impact of one of these side reactions. On the actual mechanism which

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• % CO2. RAW264.7 cells (1.6 × 105/well) were seeded in a 24-well plate overnight for cell adherence. Cells were treated with LPS alone (100 ng/mL, dissolved in DMSO) or with compounds at the indicated concentrations for 24 h. Total RNA was harvested from cells using TRIzolTM reagent (Invitrogen, USA

• ) after being washed thrice with cold PBS. The total RNA (1 μg) was transcribed into cDNA in 20 μL reactions using the PrimeScript RT reagent kit (ABclonal, China) and then diluted to 200 μL. Real-time quantitative PCR (qPCR) was performed using SYBR GREEN QPCR KIT (Bimake, B21202) on Agilent Mx3000P

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

• , and dihydrofuran. The results are summarized in Table 1. Regardless of trapping reagents, 1.3–1.4 F/mol of electricity was required to consume the starting material 1. The required electricity was similar to the electrolysis in the absence of the trapping reagent. Only when α-methylstyrene was used as

• the radical trapping reagent, the expected radical adduct 4 was formed in reasonable yield of ca. 30% (Table 1, run 1). A platinum cathode is more suitable for the formation of adduct 4 compared to a glassy carbon cathode (Table 1, run 2). Dolbier et al. reported that electron-poor perfluoroalkyl

• significantly. In this case, the required electricity was increased to 1.8 F/mol. From these results, we anticipate that a one-electron reduction of compound 1 takes place to generate the PhSCF2 radical, which is further reduced affording the PhSCF2 anion when a trapping reagent is absent. The resulting anion

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• –Prakash reagent (TMSCF3) in the presence of Cs2CO3 as base in MeCN at 0 °C gave product 7 with a trifluoromethyl group. Stefani et al. reported the 1,3-dipolar azide–alkyne cycloaddition (AAC) of organotellanyl alkynes with organic azides in the presence of a copper reagent to form 5-organotellanyl-1,2,3

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• starting bromoacetate at rt or on heating to 50 °C. The further substitution reactions, during peptoid elongation, were carried out in a 1:1 MeOH/H2O mixture (1.25 M) at 60 °C, using three equivalents of the Boc-protected hydrazine reagent. These distinct substitution conditions, together with standard

• substitution step, due to the close polarities of the products and starting hydrazine reagent. So we turned our attention to a fragment-based coupling approach for synthesizing the hexamer peptoid 6. Thus, several coupling methods were evaluated, initially starting from the hydrazine and acid monomers 1a and

• 1c, respectively (Scheme 2). The N-Fmoc-protected acid partner 1c was readily prepared from 1a under standard conditions. After a few unsuccessful attempts of coupling using the azabenzotriazole-based coupling reagent HATU [42] or via the formation of an acid chloride with thionyl chloride, we turned

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

• synthesis and application of three new members of the “dummy group” reagent family, based on the α-(perfluoroalkylsulfonyl)propiophenone scaffold for the perfluorobutylation (1a), perfluorohexylation (1b) and perfluorooctylation (1c) of electron-rich aromatics (Scheme 1). With the insights discussed in this

• perfluoroalkylating reagent that participated in such condensation (around 30%), giving us the final yields of perfluoroalkylating reagents 1a–c displayed in Scheme 3. Afterward, to show the practicality of application of these reagents in industry, we proceeded to scale up their synthesis in gram-scale

• in yields of 64% and 20%, respectively. Arenes containing halogens were attempted; however, in accordance to previous reported literature, the compounds were found to decompose under the ultraviolet radiation necessary for the homolysis of the reagent [25]. Lastly, some heteroaromatic substrates such

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• the reagent after performing the respective reaction. Given these examples, we believe that the adoption of flow techniques has a great potential to facilitate the synthesis of new scents with exciting odor profiles, while simplifying upscaling of the reaction to an industrial process. The olfactory