Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• the aromatic product 85, thereby regenerating the catalyst (Scheme 16) [61]. Given its abundance, stability, and low price, elemental sufur (S8) is an ideal source of sulfur atom to produce thiacycles [62]. In 2019, H.-T. Tang utilized this reagent in combination with (hetero)aromatic ketone-derived

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• Abstract A flow photochemical reaction system for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence was developed, which utilizes in situ-generated 2-benzopyrylium intermediates as the photoredox catalyst and electrophilic substrates. The key 2-benzopyrylium intermediates were

• generated in the flow reaction system through the intramolecular cyclization of ortho-carbonyl alkynylbenzene derivatives by the π-Lewis acidic metal catalyst AgNTf2 and the subsequent proto-demetalation with trifluoroacetic acid. The 2-benzopyrylium intermediates underwent further photoreactions with

• catalytic cycles). In catalytic cycle I, the key cationic components, 2-benzopyrylium intermediates A, are generated in situ by the activation of the alkyne moiety of ortho-carbonyl alkynylbenzene derivatives 1 in the presence of the π-Lewis acidic metal catalyst [M]X [AgNTf2 or Cu(NTf2)2] and subsequent

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• (e.g., t-BuOK) [53] or metal (Cr, Al, Fe, Ni, Mg)-based catalyst [54][55][56]. 2-Chloro-1,2-difluoroethane (HCFC-142) and 1-chloro-1,2-difluoroethane (HCFC-142a) can also be used as 1,2-difluoroethene precursors (Scheme 4) [57][61]. The dehydrochlorination reaction proceeded in the presence of metal

• catalyst (Pd, Pd, Pt, Rh, Ru, Ir, Ni/Cu, Ag, Au, Zn, Cr, Co, Scheme 5) [62][63]. Further, 1,2-Dichloroethylene was reacted with hydrogen fluoride in the presence of metal fluorides or transition metals (Cr, Al, Co, Mn, Ni, Fe) to form 1,2-difluoroethylene (Scheme 6) [56][58]. In patents [59][60], an exotic

• ) [101][102]. Our group attempted to use (E/Z)-1,2-difluoroethylene in a Heck reaction [78]. The experiments were performed using 4-iodotoluene or methyl 4-iodobenzoate in DMF, Pd(OAc)2 as a catalyst, and Et3N as a base (Scheme 25). The reactions were carried out in a stainless steel autoclave at 120 °C

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• applicable to a broad range of substrates, however, it utilizes a catalyst that is not commercially available and small heteroaromatic rings are underrepresented in the scope. Recognizing the importance of small heteroaromatic rings and the amino acid motif in medicinal chemistry [30][31][32][33], and aiming

• )acetate at the bottom of the vial after a few hours of storage in the fridge. The solid can be easily re-dissolved by gentle heating, and without affecting the product concentration and integrity. After a brief screening, Pd(dba)2 and X-Phos (in a 1:2 ratio) were selected as the catalyst system for the

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• nonmetallic reagents as an attractive alternative is less developed. In 2014, Antonchick and Manna firstly reported the synthesis of a series of 3,4-diaryl-substituted isoquinolinone derivatives through oxidative annulation between alkynes and benzamide derivatives using iodobenzene as a catalyst and

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• on different substrates, the conditions were similar: 20 mol % of the catalyst, ethanol as solvent at 80 °C in the first case, 30 mol % of catalyst, ethylene glycol at 90 °C in the second case; however, a striking difference appears when the reaction was carried out in the absence of silver catalyst

• reactions, if we exclude a 96-member library of GBB adducts reported very recently by Dömling et al. [9]. In this case, however, Sc(OTf)3 was used as the catalyst and the choice for ethylene glycol was dictated by the need to have a polar solvent with a high boiling temperature. Shankar et al., however

• discussed in more details in chapter 2). Another recent article on the use of Brønsted acids has been reported by Vilapara et al., who employed for the first time etidronic acid (1-hydroxyethane-1,1-diphosphonic acid, HEDP) as a green catalyst. Reactions were efficient at room temperature [11]; although the

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• has been successfully applied as photoredox catalyst in the synthesis of secondary or primary anilines via light-dependent desulfonylation or desulfonylation/dealkylation procedures [19]. Thus, the design of novel and efficient routes for the synthesis of 5-aryldeazaalloxazines 2 has become a

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• bifunctional sulfide (S)-1a (10 mol %) bearing a hydroxy group. This reaction yielded the desired δ-valerolactone product 3a with good yield and enantioselectivity [83% yield, 86:14 enantiomeric ratio (er)]. We further tested the reaction of 2a with a hydroxy-protected sulfide catalyst (S)-4 under the same

• conditions to evaluate the importance of the bifunctional design of the hydroxy-type chiral sulfide catalyst (S)-1a. As expected, the use of the hydroxy-protected catalyst (S)-4 produced 3a with significantly lower enantioselectivity (51:49 er). This outcome clearly underscores the crucial role of the

• , respectively). These findings led us to further optimize the hydroxy-type chiral sulfide catalysts of type (S)-1. Substituting an alkyl group on sulfur of catalyst (S)-1 with isobutyl and tert-butyl [(S)-1b and 1c, respectively] decreased enantioselectivity compared with the n-butyl group-substituted catalyst

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• preparing spiro α-methylene-β-lactones from different steroidal propargylic alcohols [13]. The procedure involves a one-pot Pd-catalyzed cyclocarbonylation of alkynols using 5 mol % of Pd(CH3CN)2Cl2 as a catalyst precursor and 30 mol % of 2-(dibutyl)phosphine-1-(2,6-diisopropylphenyl)-1H-imidazole as

• ether 39, a ring-closing enyne metathesis (RCEYM) was initiated using the Grubbs second-generation catalyst (G-II) and high temperature to obtain the spiro 2,5-dihydrofuran derivative 40 in 76% yield. Additionally, when a dienophile such as N-phenylmaleimide was directly added to the same pot and

• being the major product (81% yield). Conversely, using 121b exclusively yielded the bis-acylated product 122b1 (59% yield), which was transformed into the mono-acylated compound 122b2 upon treatment with sodium methoxide. A final ring-closing metathesis (RCM) using a second-generation Grubbs catalyst (G

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• approach, they used a chiral boron catalyst as a Lewis acid and achieved at best an endo/exo selectivity of 1.9:1 in a similar DA reaction. The use of Diels–Alderase in their recent work significantly improved the endo/exo selectivity under mild conditions in water, thereby highlighting the strengths of

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• cyanoborohydride as a mild reducing agent, and paraformaldehyde as a methylating agent [36]. Methanol can be used as the methylating reagent in other methods. Here, a palladium on carbon (Pd/C) catalyst processes the dehydrogenation of the alcohol to form the corresponding aldehyde. The subsequently formed imine

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• ) bromide, it afforded compound 2 with a very low yield (2%). When the phosphonation was performed with diethyl phosphonate in the presence of Pd(PPh3)4 as catalyst and trimethylamine, compound 2 was formed with a good yield (72%) (Scheme 1). The corresponding (4-nitrophenyl)phosphonate derivative 6 [51

• ] was also prepared, using the same reaction conditions, by the reaction between 1-bromo-4-nitrobenzene (5) and diethyl phosphonate, in the presence of Pd(PPh3)4 as catalyst and triethylamine, since the use of triethyl phosphite in the presence on nickel(II) bromide do not allow the formation of the

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• performed (reactants at 1:1:1 ratio, 10 mol % of the catalyst, MeOH, rt, 16 h). It was found that TsOH, albeit being cheaper, demonstrated a poorer performance as the reaction promotor (62% SSR vs 67% for Sc(OTf)3; 34% average yield in both cases). This is especially apparent if the product yields are

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• ][34][35][36][37][38][39][40][41][42][43]. The PEM reactor included a membrane electrode assembly (MEA) consisting of a PEM and an electro-catalyst supported on carbon (Figure 1). Humidified hydrogen gas (H2) or H2O was injected into the anodic chamber and the substrate passed through the cathodic

• for a supporting electrolyte, which is necessary for conventional organic electrolysis, reduces the environmental impact, and facilitates product purification. In addition, using nanoparticles in the catalyst layer, which serve as the electrode, results in a large specific surface area and efficient

• semihydrogenation of alkynes to form Z-alkenes using a PEM reactor [31]. The Pd/C catalyst was essential for the reaction. They recently found that a PEM reactor with a Rh/C catalyst was effective for the stereoselective reduction of cyclic ketones [40]. Nagaki et al. reported the electrochemical deuteration of

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• secondary and tertiary substrates too. In 2012, Lectka reported a fluorination of mostly aliphatic C–H bonds that used a molecularly defined copper catalyst with a bis imine ligand, along with co-catalytic N-hydroxyphthalimide and a phase-transfer catalyst [51]. Although only a few benzylic substrates were

• intramolecular fluorine-atom-transfer (FAT) from an N-fluorinated amide to a pendant carbon-based radical formed from an iron catalyst (Figure 15) [55][56]. This concept of fluorine transfer through a 6-membered transition state was shown to work efficiently from primary, as well as secondary, benzylic radicals

• photosensitive arylketone catalyst in the fluorination of phenylalanine residues in peptides (Figure 27) [72]. This work demonstrated high yields and selectivity for peptides bearing phenylalanine residues, including tripeptides, such as 16. In 2015, Britton and co-workers reported a photochemical HAT-guided

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• primary amine catalysts (see Table S1 in Supporting Information File 1) in toluene at room temperature (30–32 °C). When the test reaction was conducted in the presence of 15 mol % of 9-amino-9-deoxy-epicinchonidine (I) as catalyst [30] for 12 h and treated with Ac2O followed by DABCO, the reaction gave

• File 1), the catalyst I imparted the highest enantioselectivity (74% ee) of the Michael product 3aa (Table 1, entry 1). Different solvents (see details in Supporting Information File 1) were screened for the test reaction using 15 mol % of catalyst I. Among them, CHCl3 turned out to be the optimal

• marked increase in both the yield and enantioselectivity of the product 3aa were observed. Among the screened Brønsted acids A1–6, the combination of 15 mol % of the catalyst I and 30 mol % of (±)-mandelic acid (A5) was found to be superior in terms of enantioselectivity (92% ee) of the product 3aa

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• carbonyl compounds (Scheme 1A). Hereby different strategies using different quaternary ammonium iodide derivatives and different azide sources were investigated and especially Uyanik’s and Ishihara’s recent approach using NaN3 in combination with the carefully designed achiral catalyst C1 represents a

• ammonium iodides [40]. Interestingly, designer catalyst C1 was found being catalytically superior compared to Bu4NI (TBAI) when using H2O2 as the oxidant. Furthermore, it turned out that addition of PBN (phenyl N-tert-butylnitrone) has a beneficial effect on the reaction and that carefully buffered

• α-S(e)CN-functionalization of different pronucleophiles [39] as well as the benzylic azidation of alkylphenol derivatives with NaN3 using TBAI as a catalyst [41]. Considering the fact that TBAI clearly represents one of the most easily available quaternary ammonium iodides and keeping in mind our

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• studies we also realized that the masked β-AA derivatives 2 undergo enantioselective β-addition to allenoates 3 under chiral ammonium salt catalysis (Scheme 1B) [18]. Interestingly, hereby we also found that the use of alternative catalyst systems (i.e., tertiary phosphines) allows for a γ-selective

• addition of 2 to the allenoate instead, thus resulting in two complementary catalyst-controlled pathways [18]. Based on these previous results, and also the well-documented different reactivity trends of allenoates 3 when using different organocatalysts and activation modes [23][24][25][26][27], we were

• (Table 1, entry 7, similar non-selective results were obtained when using THF), were found to be less-suited however. Testing the 3,4,5-trifluorobenzene-decorated catalyst B2 with K2CO3 in toluene next (Table 1, entry 8) allowed for a slightly higher selectivity but still gave only a relatively low yield

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• , the corresponding alkylnitrile product was obtained in 86% yield after electrolysis at 3.0 mA for 4 hours, demonstrating the high Faradaic efficiency of the reaction (Table 1, entry 5) [46]. Control experiments revealed that Ce catalyst, Cu catalyst, light, and electricity were all essential for the

• success of this transformation (Table 1, entries 6–9). We also tested other photoredox catalysts that are capable of driving the oxidative decarboxylation, only Fukuzumi catalyst [47] was able to deliver the product with a meaningful yield (Table 1, entry 10). The scope of this transformation was next

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• Lu Li Na Li Xiao-Tian Mo Ming-Wei Yuan Lin Jiang Ming-Long Yuan National and Local Joint Engineering Research Center for Green Preparation Technology of Biobased Materials; School of Chemistry and Environment, Yunnan Minzu University, Kunming, China 10.3762/bjoc.20.130 Abstract A catalyst- and

• Morita–Baylis–Hillman (MBH) adducts [20][21], we were interested in further utilizing (E)-2-arylidene-3-cyclohexenones that can be facilely synthesized from MBH alcohols to build functionalized molecules. Herein, we wish to report our preliminary study on a catalyst- and additive-free synthesis of 2

• -substituted anilines from (E)-2-arylidene-3-cyclohexenones and primary aliphatic amines. The reaction proceeds through an imine condensation–isoaromatization approach under catalyst- and additive-free conditions, allowing the generation of synthetically useful aniline derivatives in 23–82% yields. This method

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• presented a method for the C–H thiocyanation of pyrazoles by using a sustainable catalyst of graphite-phase carbon nitride (g-C3N4) under visible light irradiation (Scheme 1c) [2]. Furthermore, Yao harnessed an electrochemical approach to form the electrophilic SCN+ intermediate, which reacted with

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• )-pentacarboxylates was developed by a three-component reaction. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile afforded polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine

• hour. In the presence of DABCO as base catalyst, the yield of 4a decreased to 27% (Table 1, entry 16). Other common bases such as Et3N and DMAP were also employed in the reaction, they did no gave the product 4a in higher yields than that in the absence of any base, which showed that the reaction does

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• possibly due to greater dispersive and lesser repulsive forces for larger halogens. This finding may prove useful in catalyst design where close spatial proximity of the substrate to other important structural information (i.e., chirality) has an impact on selectivity. Our analysis of selected XB complexes

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• of a high water amount results in catalyst deactivation. Based on these results and what was observed in the optimization tests (Table 1, entry 6), we extended the reaction time but used ACN as solvent, which possesses a higher water content with respect to DCM (experiment C, Scheme 5). Gratifyingly

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• simple lithium salts for hypervalent iodine catalyst activation. The activated hypervalent iodine catalyst allows the intermolecular coupling of soft nucleophiles such as amides onto electronically activated olefins with high regioselectivity. Keywords: amide coupling; hypervalent iodine catalysis

• ]. Notably, an interesting work by Hashimoto has recently enabled the intermolecular addition of N-(fluorosulfonyl)-protected carbamates as oxyamination reagents across a variety of olefin structures [47]. This work engages the hypervalent iodine catalyst in an anionic ligand exchange with the substrate

• , which then partitions into an ion pair suitable for olefin activation, followed by the addition of the bifunctional anionic carbamate (Scheme 1c). Our hypothesis here aims to directly access the reactivity of the cationic hypervalent iodine catalyst through an initial activation first, which we reason