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

• bromolactonization product 3a. It should be noted that the asymmetric reaction using bromine (Br2) as a brominating reagent gave product 3a in a racemic form. Additionally, iodolactonization of 2a using N-iodosuccinimide in the presence of catalyst (S)-1g was performed. The reaction in dichloromethane, however

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• alternative approach, we reported the first application of using fluoroiodane 2 as a fluorinating reagent in 2013 [11]. The chelate sidearm makes 2 an air-stable, easy-to-handle solid with excellent fluorinating ability and it often exhibits different reactivity to that observed with fluoroaza reagents such

• bromine trifluoride (Scheme 2B) [21][22]. They also showed that hypervalent iodine(V) fluoride 3 fluorinated phenylmagnesium bromide in Freon-113 to form fluorobenzene in 90% yield (Scheme 2A) and so, it is very surprising that this reagent has not been investigated further. Since then, Gruber [23

• fluorinating reagent (Table 1, entry 5). When 8 was reacted with 4 equivalents of freeze-dried Selectfluor in dry acetonitrile at 40 °C for 48 hours, difluoroiodane 6 was formed in 85% spectroscopic yield. However, the iodosyl decomposition product 9 was also produced in 15% spectroscopic yield, despite

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

• compounds were hydrogenated, oxidized, and lactonized in a similar fashion, utilizing either the Jones reagent or manganese dioxide as the oxidizing agent [18]. Santhamma et al. developed another route for steroidal spiro-γ-lactones at C-17, from estran-17-one and androstane-17-one derivatives [19]. The

• Lawesson's reagent (LR), yielding chemoselectively 1,2,4-trithiolane dimers 94a–e [50]. The reaction led to the formation of diverse sulfur products, including (di)thioketones, dimeric sulfides, and (4-methoxyphenyl)phosphonotrithioates contingent on reaction time and solvent used. Refluxing unsaturated

• -oxathiaphospholane steroids In 2012, Krstić et al. reported the synthesis of spiro-1,3,2-oxathiaphospholane steroids using Lawesson’s reagent (LR) as a thionating and phosphorylating agent in the reaction with 17α-hydroxyprogesterone (107) [58]. The reaction was conducted in toluene, dichloromethane, or carbon

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

• [34]. In reductive amination, the substrate is usually an aldehyde or amine. After the formation of the iminium ion, it is reduced with the appropriate reagent to form the N-methylated amino acid. Different methods have been established using for example benzaldehyde as a protection group, sodium

• 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

• triethylsilane in TFA-CH3Cl, resulting in the N-methylated amino acid as the final product [38]. The third method for chemical N-methylation involves the use of protection groups that also enhance the reactivity of the primary amine (Figure 2). Once the amine is deprotonated, an electrophilic methylation reagent

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• generated in situ simply by mixing PIFA with a Lewis acid, in this case AlCl3. The importance of this protocol arises from the oxidation of an AlCl3-based chlorine atom, which is an available and cheap reagent. Then it is used as an electrophile source in the chlorination process with an umpolung reactivity

• . In contrast to the suggested traceroute where the chlorine or bromine atom is attached to the hypervalent iodine center of the plausible reagent PhIX2 (X = Cl, Br), our new protocol opens up a broad path for the reaction through different halogenating species. For a deeper understanding of these

• reaction pathway. The first explored mechanism involves PIFA/AlCl3 and the second PIDA/AlCl3 (see Figures S2 and S3, respectively, Supporting Information File 1). In both cases, the route involves the formation of PhICl2 as the chlorinating reagent by considering two equivalents of AlCl3 (PIFA/AlCl3 or

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• were prepared to match the core amino acids of the predicted ceanothine B and CAM603 cyclopeptide alkaloids. To make each amino acid standard, 0.2 mg of the ʟ- and ᴅ-amino acid was aliquoted into separate reaction vials. To each vial, 50 µL of water, 20 µL of 1 M NaHCO3, and 100 µL 1% Marfey’s reagent

• . Afterward, 25 µL of water, 10 µL of 1 M NaHCO3 and 50 µL of 1% Marfey’s reagent in acetone were added to the reaction vial. The reaction was incubated for 1 h at 40 ºC with periodic agitation. The reaction was quenched by adding 5 µL of 2 M HCl and dried under a nitrogen stream. The dried peptides were

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

• mechanism. Excess NFSI functioned as both a fluorine source and HAT reagent precursor (Figure 13) [20]. Fluorine abstraction from NFSI by copper(I) generates an N-centred radical that is selective for benzylic C(sp3)–H bonds [52][53], affording the benzylic radical via HAT. Subsequent FAT with the in situ

• detailed metal-free radical C(sp3)–H fluorinations suitable for benzylic substrates. These typically involve the generation of a HAT reagent that is selective for benzylic C–H bonds and facilitates the generation of a benzylic radical. Subsequent FAT, from a fluorinating reagent, yields the desired benzyl

• fluorides. In 2013, Inoue and co-workers demonstrated the use of catalytic N,N-dihydroxypyromellitimide (NDHPI) as a precursor for N-oxyl radicals that serve as the HAT reagent. Selectfluor was employed as the FAT reagent, generating an N-centred radical on the spent Selectfluor that can regenerate the N

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

• reagent/catalyst system allows indeed for high yielding direct α-azidations of different (cyclic) β-ketocarbonyl derivatives (Scheme 1C), thus resulting in an operationally simple protocol to access α-azidated carbonyl derivatives. In addition, we have also carried out some test reactions using NaNO2

• stoichiometry and catalyst loading (Table 1, entries 11–15). Hereby we found the use of 1.2 equiv of NaN3 with 1.2 equiv of DBPO and 20 mol % Bu4NI as the best-suited and most economic reagent/catalyst combination, which allowed for the synthesis of 2a in high isolated yield on 1 mmol scale as well (Table 1

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

• available CeCl3 (10 mol %) and Cu(OTf)2 (5.0 mol %) together with bidentate nitrogen ligands such as BPhen, Phen, dtbbpy, and bpy with TMSCN as the cyanating reagent promoted the direct conversion of flurbiprofen (1) to the desired product (2) in good yields (Table 1, entries 1 and 2). Cu ions are well

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• alkenes. We previously developed a dihomohalogenation method using selectfluor as an oxidant [27]. Herein, we synthesized bicyclic oxy- and alkoxyfluorine compounds using selectflour as an electrophilic fluorination reagent, water and various alcohols as an nucleophile. Results and Discussion In this

• . An environmentally friendly approach was pursued by using safe, easily soluble, easy to use, stable, solid and reactive selectfluor as an electrophilic fluorination reagent, and water and various alcohols as a nucleophile source. Besides being novel, the presented oxyfluorination protocol provides

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• great importance of these strategies, the direct use of acids or alcohols is more fascinating as this approach circumvents the additional synthesis of special functionalized compounds. The strategy involves in situ activation by appropriate reagent, followed by photochemical C–O bond scission to

• . Appropriate selection of the phosphine reagent was the key to success in the process. Due to the lower oxidation potential, electron-rich PMe2Ph preferentially transferred a single electron to the excited state of the photocatalyst rather than the alkene, which was essential for obtaining the desired product

• ][40][41][42]. However, these protocols have a limited scope and suffer from prefunctionalization and waste generation. Photons are considered the greenest reagent in organic synthesis. Thus, photomediated alkyl radical generation from easily accessible alcohols for organic synthesis is highly

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• and Discussion Methodology development In our work towards Rh-catalyzed homo-coupling reactions of benzyl halides, we observed that a similar rhodium–bis(benzyl) complex can also be formed from benzyl halide by using a Grignard reagent instead R2Zn in the presence of RhCl(PPh3)3 to subsequently give

• solvent as the best conditions (Table 2, entry 1). As shown above, the commercially available Grignard reagent 4a gave the corresponding homo-coupled product 3a in a short reaction time at room temperature. Subsequently, for the purpose of expanding the scope of substrates, we examined the in situ

• preparation of the Grignard reagent followed by the homo-coupling reaction. Various conditions were examined and biphenyl (3b) was obtained in 85% yield in a one-pot reaction, when bromobenzene (5b) was treated with 1.5 equiv of Mg (turnings, grade for Grignard reaction) under reflux conditions of THF for 24

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• increase in the yield of product 4b (Table 1, Entry 11). At the same time further prolongation of the reaction did not affect on the obtained results (Table 1, entry 12). It is important to emphasize that basic reagent is necessary for the considered rearrangement. For example, reflux in EtOH or AcOH for 6

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• chemical reagents; however, these methods have some drawbacks, such as reagent toxicity/stability and limited substrate scope [12][13][14]. While recent advances in photochemistry have remarkably expanded the synthetic utility of (hetero)aryl radicals in organic synthesis [15][16][17][18][19][20], visible

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• variables to counteract the formation of 3a and 3a’. We first envisioned that the use of the more hindered, mesityl-derived Koser’s reagent, could drastically influence the formation of the side-products. Unfortunately, its use resulted in a drop of the yield for the desired α-bromoketone (Table 1, entry 2

• ). In situ generation of Koser-like reagent by addition of excess TsOH·H2O (2.0 equiv) to either PIDA or p-OMe-PIDA did not further improve the yield for α-bromoketone (Table 1, entries 3 and 4). We envisioned that altering the iodonium intermediate counterion by replacing TsOH with either MsOH or HNTf2

• ). We then explored catalytic conditions for the generation of the iodine(III) reagent. Remarkably, when catalytic PhI (0.2 equiv) was employed for in situ generation of Koser’s reagent by using m-CPBA (1.2 equiv) as an oxidant, almost similar results were obtained (Table 2, entry 1) with those obtained

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• converted to indano[60]fullerene thioketone (FIDS) in high yield by using Lawesson's reagent. Three compounds with different substituents in para position were successfully converted to the corresponding thioketones, showing that the reaction tolerates compounds with electron-donating and electron

• fullerene cation chemistry as reported by our group [20][21][22][23][24][25][26]. Conversion from ketone to thioketone is usually achieved by using Lawesson's reagent, which tends to form a trimer structure when reacted with indanone without a substituent at the α position [27][28][29]. Introduction of

• fullerene at the α position facilitated the successful transformation of ketone to thioketone. Initially, we adopted the widely reported reaction conditions with 1.5 equiv of Lawesson's reagent and tetrahydrofuran (THF) as solvent. t-Bu-FIDO was dissolved in THF by sonication for 30 min. Unfortunately, the

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• chromones requires the action of trimethylsilyl trifluoromethanesulfonate (TMSOTf) which is a relatively expensive reagent. In future studies, especially the chemistry of 3-methoxalyl- and 3-nitrochromones should be further explored. In case of the methoxalyl derivatives, so far not many synthetic

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• calculated respectively for C60, 2, and 3. Experimental Materials and general method: All chemicals were reagent grade, purchased from commercial suppliers. o-Dichlorobenzene (ODCB) was distilled from P2O5 under vacuum before use. Toluene was distilled from benzophenone sodium ketyl under dry N2 prior to use

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• aryl/benzyl polybromides are also well known. Looking at this subject, the number of found reaction hits (role = reagent) for the structure “as drawn” provides a quantitative measurement of the synthetic usefulness of these halides. This work focuses on the application of the peroxide-bromide method to

• anhydrous HBr. A notable increase in selectivity towards 3b was suddenly observed (Table 2, entry 8). However, this method led to the undesired, uncontrolled generation of Br2 when neat H2SO4 was mixed with NaBr. This issue was addressed through an alternative reagent introduction scheme, where NaBr was

• dissolved in aqueous hydrogen peroxide and was gradually added to the reaction mixture, containing the remaining chemicals. The addition time of this aqueous reagent was also shortened to 15 minutes, to counteract the slow decomposition of H2O2 caused by NaBr. This modification ultimately resulted in nearly

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• hexaketocyclohexane octahydrate as the CO source again. This cyclic hexaketone is a non-toxic stable solid and therefore, it is simple and safe to use unlike of carbon monoxide. It was used as reagent to obtain indol-α-ketoesters by the Cu-catalyzed direct double-carbonylation of indoles and alcohols [76]. The

• catalysts. Therefore, Wu’s group developed the direct C–H aminocarbonylation of indoles by using cheaper Co(OAc)2·4H2O as catalyst [80] which allowed the reaction to proceed well when used in conjunction of Ag2CO3 as oxidant and a further addition of PivONa as additive. The presence of CO as reagent was

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• Kingdom 10.3762/bjoc.20.82 Abstract 2-(Trifluoromethylthio)benzothiazolium triflate (BT-SCF3) was used as deoxyfluorinating reagent for the synthesis of versatile acyl fluorides directly from the corresponding carboxylic acids. These acyl fluorides were reacted with amines in a one-pot protocol to form

• different amides, including dipeptides, under mild and operationally simple conditions in high yields. Mechanistic studies suggest that BT-SCF3 can generate acyl fluorides from carboxylic acids via two distinct pathways, which allows the deoxyfluorinating reagent to be employed in sub-stoichiometric amounts

• to deliver acyl fluorides via two distinct deoxyfluorination pathways, an efficient process could be achieved using only sub-stoichiometric amounts of the fluorinating reagent. Results and Discussion In an initial test reaction, 4-methylbenzoic acid (1a) was reacted with 1.25 equiv of BT-SCF3 and 2.0

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• highly diverse peptidic structures A with up to four points of substitution (Scheme 1) [26][27]. By replacing the carboxylic acid with a nucleophilic azide reagent XN3 (generally TMSN3), the Ugi-azide four-component reaction (UA-4CR) of an aldehyde, amine, isocyanide, and azide gives 1,5-disubstituted 1H

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• ). Observing no byproducts originating from phenylacetylene, we speculate that the lack of reactivity stems from the relatively low electron density of the terminal alkyne, which likely leads to direct coordination of pyrazole to the iodine(III) reagent. To probe the relative reactivity of different azoles

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• and aldehyde protecting groups. Recently, Lebold, Sarpong, and co-workers showed that 1,2-BCPs (±)-14a–e are also accessible from 1,5-disubstituted 2-azabicyclo[2.1.1]hexanes 13 (2-aza-1,5-BCHs) through a skeletal editing strategy utilising commercially available Levin’s reagent [30][31] (Scheme 1D

• ). Reaction with a Grignard reagent, hydroboration and oxidation of the organoborane were also possible in high yields (to 188). Similar to ketoprofen bioisostere 189, its inversely substituted isomer iso-189 was also accessible from 185a. Iwabuchi and co-workers also investigated the biological activity of

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• , respectively. The formation of all three products 9–11 can be explained as follows (Scheme 2A) [28][29][30][31]: Due to the favorable formation of cis-5,5-fused B/C ring system, the borane reagent is preferred to approach the double bond of 1 from the α-face, to give either a secondary 1-organoborane