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

• recent achievements on the synthesis and functionalization of indole derivatives via carbonylative approaches. Keywords: carbonylation; functionalization; indole; metal catalyst; organometallic chemistry; Introduction Indole is a heterocyclic compound consisting of a benzene ring fused with a pyrrole

• 1883 and involves its synthesis from phenylhydrazine and an aldehyde or ketone using an appropriate acid catalyst [8]. In the following years, new processes were developed for the synthesis of indole such as the Castro, Bischler, and Larock synthesis etc. [2][9][10]. Carbonylation reactions represent a

• carbon monoxide insertion, and Suzuki–Miyaura coupling reaction, from 2-gem-dibromovinylaniline [12]. In the presence of Pd(PPh3)4 (5 mol %) as catalyst, 5 equivalents of base (K2CO3), an aryl- or heteroarylboronic ester (1.1 equivalents), CO (12 bar), in dioxane at 100 °C after 16 h the indole

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• all other lactams as R was done by analogy. The assignment of the absolute stereochemistry allowed us to propose a rationale for the Heck–Matsuda reaction (Scheme 7). Upon activation of the catalyst (I), oxidative addition of aryldiazonium salt and subsequent nitrogen release generates the cationic

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• -coupling was carried out using Pd(PPh3)4 as catalyst with K3PO4 as base in toluene as solvent which gave a mixture of different products. Further investigation revealed the presence of the two-fold Sonogashira–Hagihara product, starting material 2, and the desired product 3. Hence, starting material 2 and

• be activated, and the 5-position deactivated for the nucleophilic attack that occurs during the oxidative addition of the metal catalyst. This may explain the formation of only the 6-substituted product during the Sonogashira reaction. As mentioned above, new reaction conditions had to be chosen to

• synthesize the desired product 4 and to avoid a mixture. A different catalyst and a higher temperature were chosen to obtain the desired products in higher yields. With the optimized conditions in hand (Pd(CH3CN)2Cl2 (5 mol %), CuI (5 mol %), NEt3 (10 equiv), dioxane, 100 °C, 6 h), the scope was investigated

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• , herein, we utilized a copper catalyst to activate the C–I bond of diaryliodonium salts in the generation of aryl radicals, thus resulting in an annulation reaction with naphthols and substituted phenols. This approach yielded a diverse array of 3,4-benzocoumarin derivatives bearing various substituents

• diaryliodonium salt 2a. Naphthol 1a forms intermediate B with A after participation with the Cu(II) catalyst. Intermediate B generates C by radical substitution. A final intramolecular transesterification yields the benzocoumarin product 3aa. Conclusion In summary, we have employed ortho-ester-substituted

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• leading to anti-Markovnikov products via several pathways. We have chosen not to present a fourth class of reactions involving either HCl gas or CuCl2 and a Pd catalyst, as reported by Alper [20] and Sigman [21], as these reactions are somewhat exotic and are sufficiently discussed in Yang’s review [14

• solution of HCl, even in the presence of secondary alcohol and ester functionalities (Scheme 5B) [45]. An application in the synthesis of Δ9-tetrahydrocannabutol, the butyl homologue of Δ9-tetrahydrocannabinol (Δ9-THC), is outlined in Scheme 5C [46]. In this case, ZnCl2 was employed as a catalyst, but

• unfortunately data in the absence of ZnCl2 was not provided by the authors. ZnCl2 has been previously reported as a catalyst for hydrochlorination reactions, notably in the case of cyclooctene (25) with HCl in benzene (Scheme 5D) [47]. The use of ZnCl2 as a catalyst for hydrochlorinations dates back to a patent

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

• ]. Moreover, different azide sources are known to efficiently promote the diazidation of alkenes in the presence of a copper catalyst, often proceeding via a radical mechanism [24][29][30][31]. A second approach would involve SOMOphilic alkynes to trap the radical by a purely open-shell mechanism (Scheme 1B

• since it is known to be reduced by photocatalysts such as Cu(dap)2Cl [17]. This perfectly fits a catalytic cycle involving the reduction of Ts-ABZ (3) followed by oxidation of the carbon radical to form a carbocation and regenerate the ground state catalyst. Styrene (1a) was used as model substrate

• a non-complexed copper catalyst formed during the transformation [24][51]. When iridium-based photocatalysts were tested, no product formation or only traces were observed (Table 2, entries 2 and 3). Using Ru(bpy)3Cl2·6H2O afforded 17% of 4a, a similar yield as with Cu(dap)2Cl with a reduced

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• chiral metal complex catalyst but also as an enantioselective organocatalyst [17]. Accordingly, its application in enantioselective organocatalysis, particularly in asymmetric reactions through “enamine activation”, warrants further investigation. Results and Discussion The corresponding copper(II

• (i.e., temperature, reaction time, amount of catalyst, solvent) were adopted from the pilot study [5] for relevant comparison of catalyst characteristics. From Table 1 and Table 2, which summarise results obtained using tridentate ligands Ia–c and IIa–c, it is evident that the catalytic activity their

• , the other afforded the nitroaldols with ee values of 60–90%. Finally, the complexes of ligands with cis-cis configuration (Ic and IIc) were evaluated. These catalyst are the most efficient catalysts, producing nitroaldols with very high enantiomeric purity (approx. 90–95% ee). This finding contrasts

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• experiments indicated that ligand, palladium, light and argon atmosphere were necessary for this transformation (Table 1, entries 2–5). Heating conditions could not facilitate the reaction instead of light conditions (Table 1, entry 6). The efficiency was maintained with another Pd(II) catalyst Pd(PPh3)2Cl2

• (Table 1, entry 7), whereas only low yields of 4a were observed with Pd(0) catalysts Pd(PPh3)4 and Pd2(dba)3 (Table 1, entries 8 and 9). Moreover, adding potassium carbonate as additive failed to furnish 4a, demonstrating that the trace amount of acid from the Pd(II) catalyst may facilitate the formation

• (PPh3)2Cl as catalyst, the model reaction also afforded the corresponding product 4a in 31% yield, demonstrating the H–Pd(II)–X species could be a possible catalytic species (Scheme 4d). According to the UV–visible spectra, the only absorbing species at 467 nm consists in the pre-catalytic system Pd(OAc

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• acid catalyst; thermal [2 + 2] cycloaddition; Introduction Chemical functionalization of fullerenes is a fascinating and extensively studied approach, playing a pivotal role in fullerene-based materials science to introduce various characteristic functionalities [1][2][3][4][5][6][7]. Significant

• approaches have diligently explored the details of reaction kinetics, quantitatively elucidating the impact of encapsulated Li+ on the reactivity of the outer fullerene cage as a specialized “encapsulated” Lewis acid catalyst [10][11]. While previous studies have revealed valuable insights, such as

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• expensive, extremely dangerous, strong oxidizing, and even explosive. In this scenario, heteropolyacids emerge as greener and safer alternatives due to their very strong Brønsted acidity. In particular, phosphotungstic acid (HPW) is an economical and green attractive catalyst for being cheap, non-toxic, and

• is known for its chemical and thermal stability. Herein, we report a straightforward approach to the GBB-3CR using HPW as catalyst in ethanol under microwave (μw) heating. This convenient environmentally benign methodology is broad in scope, provides the heterobicyclic products in high yields (up to

• 99%), with a low catalyst loading (2 mol %) in only 30 minutes, and allows the successful use of aliphatic aldehydes, substrates not so frequently explored with most usual catalysts for this reaction. Furthermore, the aforementioned advantages make this methodology very attractive and superior to the

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

• introduce a formamide motif in place of the amine or imine to allow the use of more forcing cyclisation conditions (Scheme 1a, path c). Oxazole 8a was obtained in good yield from 1a using only a slight excess of nitrenoid 7 and 2 mol % catalyst loading. Heating 8a in the presence of POCl3 afforded the 3

• ], intramolecular cyclisation [36] or a mixture of both [8][37][38][39]. The new ligand system proved to deliver competent catalysis. Conversion was seen in all cases at 1 mol % catalyst loading (Scheme 3). Use of 13 resulted in a slight increase of the anti-Markovnikov hydration product 17 over 18 when compared to

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 7b was formed together with disulfide 18b and aminoborane 17b (Table 1, entry 11). We thus evaluated B(C6F5)3 as a nonmetallic catalyst to activate ammonia borane in the reductive hydrogenation of the C=N-bond in [1,3]thiazolo[4,5-b]pyridines 5 and 15c. In line with reports on the hydrogenation of

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• proximity of the metallic centers which allows MMLCT transitions. These properties have been used to generate reactive oxygen species (ROS) and efficient photocatalytic oxidative cyanation of N-phenyl-1,2,3,4-tetrahydroisoquinoline. The photocatalytic activity of the catalyst could be allosterically imbibed

• protecting arms to move away from the salen complex thereby exposing the catalytic site. This triple-layer catalyst was applied in the control of a ring-opening polymerization reaction. The open state achieved full monomer conversion, while the closed state exhibited minimal activity (7% conversion after 100

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• require geminal substitution or backbone heteroatoms, internal alkenes are often not tolerated, and intermolecular reactions require high temperatures which can lead to significant catalyst decomposition [20]. This is usually addressed by employing bulky or strong donor ligands [21][22]. Novel strategies

• tackle catalyst stability by changing the chloride scavenger [23] or adding other coordinating moieties [24][25]. Hartwig et al. have argued that a Brønsted acid generated in situ from metal triflates may be the “real” catalyst promoting some alkene functionalizations [26]. Therefore, the possibility of

• concentration of deuterated species and large solvent KIE’s when performed in pure CH3OH versus CD3OD. Connections between catalyst activity and decomposition were made and a structurally interesting new bisphosphine–gold complex was isolated. Although our results do not provide conclusive evidence for or

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• 1a-enol to occur, where the enolate of 1a can react with fluorine to afford 2a and fluoride ion (Scheme 4). The resulting fluoride ion can then act as an additional, stronger base catalyst to facilitate further enolization processes and thus form 3a. Similar arguments are also applicable to the

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• defluorosilylation product was obtained [11]. In a related study of the hydrosilylation reaction of olefins 1a,b, it was shown that, depending on the catalyst used, platinum or rhodium compounds, along with the products of the addition of silane to the double bond, the elimination of the fluorine atom occurs with

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• -worker described the reaction of 1,8-diiodonaphthalene with arylboronic acids using PdCl2(dppf) as catalyst for the synthesis of various substituted fluoranthenes (Scheme 1a) [19]. In 2009, Quimby and Scott reported the use of 5,6-dichloro-1,2-dihydroacenaphthylene for the preparation of fluoranthene

• derivatives (Scheme 1b) [21]. In the course of this reaction 20 mol % of Pd catalyst, 50 mol % of phosphine ligand and 30 equiv of DBU as base were used to afford the desired fluoranthene derivatives. 1-Naphthylboronic acid and 1,2-dibromobenzene in the presence of Pd2(dba)3 (20 mol %) and PCy3 (80 mol

• these reactions require high catalyst or base loadings, and offer a very limited scope regarding the use of reagents featuring functional groups useful in organic synthesis. Consequently, the discovery of simpler and more efficient synthetic procedures for the preparation of fluoranthene derivatives

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• catalyst due to present moisture or formation of adducts with the substrate, long reaction times, lower yields, and production of large amounts of toxic waste during work-up. The general mechanisms of protic acid and Lewis acid-catalyzed syntheses of BIMs is shown in Scheme 2. In either case, the first

• step involves the activation of the carbonyl group by the catalyst. This renders it susceptible to a nucleophilic attack from the indole, leading to the formation of the intermediate product. Subsequently, a second nucleophilic attack occurs by another molecule of indole, yielding the final BIM product

• counterparts, due to their recyclability, ease of handling, and low cost [40]. Carbon-based solid acid catalysts especially are an interesting catalyst class, because they display low corrosiveness, toxicity, and higher catalytic activity, while also being insoluble in most organic solvents. The large amount

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• stoichiometric electron donors, the presence of a TM catalyst, the formation of a charge-transfer complex, and the overall reaction conditions. While we hope that this discussion will spur the continued development of NHPI esters in complexity-generating transformations, it is not comprehensive, and we refer

• the chiral phosphate co-catalyst (Scheme 5B). This event leads to the generation of a potent IrII reductant that begins the photocatalytic cycle by reducing 16 into radical anion 17 while regenerating the ground state of the IrIII photocatalyst. After fragmentation, α-amino radical 18 was proposed to

• undergo addition to the heterocyclic radical acceptor 19 through a ternary transition state 20 involving hydrogen bonding interactions with the chiral phosphate co-catalyst. Notably, a follow-up report revealed that the radical addition is reversible, and that the selectivity determining step involves the

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• formation [6]. In turn, without an acidic catalyst, it is driven by the distribution of the electron density (Figure 1), such that the nucleophilic attack occurs at the most electrophilic C(2) center. With this in mind, we presented a convenient procedure for the SNH reaction of aromatic amines with

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• of a metal catalyst [46]. Results and Discussion With these considerations in mind, we investigated the possibility of the thioetherification between alkylthianthrenium salts and thiophenols. After extensive screening of the reaction parameters, the desired thioetherification product 3aa was obtained

• using nucleophiles directly, without the need for an external metal catalyst. Synthetic application of thianthrenium salts. Substrate scope. Reaction conditions: alkylthianthrenium salts 1 (0.3 mmol), thiophenols 2 (0.2 mmol), DIPEA (0.4 mmol) in 2.0 mL of MeCN at room temperature for 16 h under air

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• simple compounds. In particular, catalytic domino reactions and one-pot processes with excellent selectivity and functional-group tolerance are of significant interest to industrial and academic research. In the so-called domino reactions, all of the required reagents, the catalyst, and a solvent are

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• this case, hydrolytic degradation of chloranil also occurred during crystallization (base 5 could act as a catalyst for such degradation), because of which yellowish needles were obtained (neither 5 nor chloranil crystallize in this form), which turned out to be the hydrochloride dihydrate of compound

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• -9a and Z-9d in benzene solution. Interestingly, the order of acceleration was primarily dependent on the basicity of the catalyst, unless the steric hindrance of the amine became a significant factor, as is the case of diisopropylamine and trimethylamine. Compounds 9d and 9e are the first examples of

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• efficient way for the synthesis of β-trifluoromethyl β-diacylamino esters. Furthermore, this reaction represents the first example of a Mumm rearrangement of β-trifluoromethyl β-diazo esters. Keywords: β-carbonyl diazo; copper catalyst; fluoroalkyl diazo; Mumm rearrangement; unsymmetrical β-diacylamino

• temperature proceeded to afford the desired unsymmetrical β-trifluoromethyl diacyl-β-amino ester 4a in 54% yield (Table 1, entry 1). The loading amount of catalyst CuI plays a crucial role in the formation of the desired product 4a. Increasing the loading amount of CuI, the yield could be raised to 66% when

• 20 mol % of CuI was used as catalyst (Table 1, entries 2 and 3). However, further increasing the amount of the catalyst led to an obvious decrease in the yield of product 4a (Table 1, entries 4 and 5). Variation on the reaction temperature also afforded the corresponding product 4a but failed to