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

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• instructions. Nitrite concentrations were determined by reacting 25 μL aliquots of reaction sample with 25 μL of deoxygenated Griess reagent R1 (1% sulfanilamide in 5% H3PO4) followed by addition of 25 μL of deoxygenated Griess reagent R2 (0.1% naphthylethylenediamine dihydrochloride in water). The absorbance

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• hydrochlorination products in acceptable yields but that trimethylchlorosilane (TMSCl) was generally the most useful reagent (Scheme 9). The reactions were typically conducted at room temperature, as elevated temperatures led to a decrease in yield, and lower temperatures were prohibited by the freezing temperature

• acetic acid as a mild hydrochlorination reagent (Table 8) [72]. Notably, the addition of acetic acid substantially enhanced the yield of chloride 109 (Table 8, entry 3). The functional group tolerance of the reaction appears to be similar to the one reported by Snyder [69] (compare Scheme 17 and Scheme

• noteworthy that Tanemura demonstrated that hydrochloric acid in the absence of silica gel gives only very sluggish reactions (Scheme 21B). This is probably the reason why hydrochloric acid was ignored as a reagent for hydrochlorination reactions for more than a century. Most recently, our group revisited the

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• a similar peptide (GABA-(Lys)5-peptide-PEG) on resin for the reaction with compound 3. Initial trials, using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and N-methylmorpholine (NMM), respectively, as a coupling reagent and a base, and 5 equiv of peptide on

• (32%) when HBTU was used as a coupling reagent. Finally, use of a greater excess (6.0 equiv) of peptide on resin relative to 3, and a combination of HBTU and DIPEA as the coupling reagent and base, provided the C60–peptide conjugate in an isolated yield of 41% (based on the used compound 3). The yield

• measured by the ESR spin trapping method under irradiation of visible light (527 nm green LED). 4-Oxo-TEMP was used as a spin trapping reagent to form an adduct with 1O2, i.e., 4-oxo-TEMPO, which was observed by ESR (Figure 7b). As shown in Figure 7a, upon visible light irradiation, three peaks

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• iodine reagents [15][16]. Azidobenziodoxolone, also known as Zhdankin reagent, has often been used under thermal or photochemical conditions to generate the desired azide radical in a controlled fashion. However, recent safety issues arising from the shock and impact sensitivity of the compound led to

• the development of the azidobenziodazolone scaffold [17]. This class of derivative showed an improved safety profile while retaining the redox properties of the original reagent. A single example of azido-alkynylation has been reported by Ramasastry and co-workers during a mechanistic study for an

• as raw data in our previous work [45]. Results and Discussion SOMOphilic alkynes We started to investigate the azido-alkynylation of styrene (1a) using EBX reagent 2 as SOMOphilic alkyne (Table 1). Tosyl-azidobenziodazolone (Ts-ABZ, 3), previously developed by our group [17], was selected as an azide

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• Andrew D. Gillie Matthew G. Wakeling Bethan L. Greene Louise Male Paul W. Davies School of Chemistry, University of Birmingham, Birmingham, B15 2TT, UK 10.3762/bjoc.20.54 Abstract A polysubstituted 3-aminoimidazo[5,1-b]oxazol-6-ium framework has been accessed from a new nitrenoid reagent by a two

• incorporating the unsaturated oxazole counterparts has not been explored. Results and Discussion Reaction of ynamide 1a with the N-acylpyridinium-N-aminide reagent 2 proceeded in good yield to afford oxazole 3 bearing a C-2 methyleneamino moiety as the first example of a free secondary amine in this annulation

• good yield. The new nitrenoid reagent 7 is readily prepared from 2,6-diisopropylphenylamine in three steps. Alkylation with methyl bromoacetate is followed by formylation of 11 and then substitution [21] of 12 with N-aminopyridinium iodide to yield the bench-stable and crystalline N-acylpyridinium

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• approach using propiolic acids [39]. The diazo reagent 1a was introduced in the Rh2(esp)2-catalyzed insertion into the O–H bond of phenylpropropiolic acid (9а) to form the intermediate compound 10a (Scheme 2). The cyclization of the latter was carried out in DCM solution under the action of DIPEA (30 mol

• structure of product 3b has been confirmed by crystallographic data. An approach to the construction of the THF cycle using a diazo reagent and 3-bromopropan-1-ol (13) [41] or similar halogenated OH substrates [42] has already been demonstrated in the literature using selected examples. We first validate

• reaction products using diazo reagent 1b as an example, but we failed to observe the formation of spirocyclic cyclization products as a result of intramolecular substitution of the bromine atom (Scheme 7). For example, during the attempted cyclization of compound 18, obtained from 2-(bromomethyl)benzoic

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• ]pyridine (13c, 54% combined isolated yield). As shown for N-acylated target compounds 16a–f, the acylation of 6-bromo-2,3-dihydro[1,3]thiazolo[4,5-b]pyridines 13a–c, affording target compounds 14a–c, proceeded under mild conditions with a suitable acyl chloride reagent and triethylamine as base in DCM. It