A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

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

• the blue region. This complex then accelerates the oxidative addition of the aryl halide to the metal, which is usually the rate-limiting step for palladium-catalyzed cross-couplings. Based on these results we decided to perform all Negishi reactions under blue light irradiation. With the optimized

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

• halogen-bond formation by the linear combination of the % p-orbital character on the halogen and energy of the σ-hole on the halogen-bond donor. Keywords: aryl halide; diarylhalonium; halogen; halogen bond; non-covalent interaction; Introduction Halogen bonding has emerged as an important attractive

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

• terminal arylalkynes bearing electron-donating and electron-withdrawing substituents were well compatible with this method. The procedure is limited to electron-withdrawing and electron-neutral aryl halides. The presence of a conjugated substituent in the p-position of an aryl halide is crucial for

• metallaphotoredox catalysis (Scheme 19). Therein, alcohols were activated by the use of NHC salts. This activation facilitated the construction of C–C bonds when combined with aryl halide coupling partners. A diverse array of alcohols and various medicinally important aryl and heteroaryl halides reacted well in

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

• utility is frequently restricted due to various challenges, such as RAE decomposition and a limited aryl halide scope. In recent years, the Baran lab has made progress in enhancing the practicality and applicability of electrochemically driven decarboxylative couplings involving NHPI esters and aryl

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• electron transfer (conPET) mechanism (Figure 4C), PDI is photoexcited and reductively quenched by Et3N to form its stable, colored radical anion PDI•− that can be photoexcited again to generate an even stronger reductant; *PDI•− (*E1/2 = −1.87 V vs SCE) [34]. A SET process to the aryl halide regenerates

• -poor aryl halide substrates (Figure 11C). While trialkylamines like Et3N or DIPEA have been proven to be suitable terminal reductants in conPET chemistry [15][45][46][51][54], they may still decrease photoreductant activity via back electron transfer [56], in contrast to CO2•− which has an entropic

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• pyridine to form aryl–Pd(II) species 140 via intermediate C. Subsequently, oxidative addition takes place in the presence of the aryl halide to give the Pd(IV) complex 141 followed by reductive elimination furnishing 3-arylpyridines 138. Almost at the same time, Yu and co-workers reported the selective Pd

• . The proposed mechanism (Scheme 29b) involves the oxidative addition of the aryl halide to the Pd(0) complex in the presence of base ligand to afford 153. Subsequently, the substitution of the halide by pyridine 1 provides the intermediate 154 which undergoes C–H activation followed by reductive

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• derivatives follow standard reactions of secondary arylamines and as such will be only briefly discussed with selected examples. Huang and Buchwald [73] reported a palladium-catalysed arylation of 1a. Treatment of 1a with aryl halide 140 or 141 gave excellent yields of N-aryldibenzo[b,f]azepines 142 (Scheme

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• order to obtain higher yields in the intramolecular cyclization step, the authors also investigated the use of a strategy based on an SNAr reaction using an electron-deficient aryl halide. Thus, 4-fluoro-3-nitrobenzaldehyde (118) was subjected to the Still–Gennari reaction, to give the corresponding cis

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

• between a primary alkyl halide and a trialkyl phosphite, first reported in the late 1890s, the general scheme for which can be seen in Supporting Information File 1, Scheme S1 [22]. It should be noted that this reaction is not suitable for use with aryl halide substrates due to the poor reactivity between

• -coupling reaction is carried out by placing the aryl halide and the precatalyst into a round-bottomed flask in the presence of a suitable solvent, such as 1,3-diisopropylbenzene or mesitylene, and setting to reflux. The advantage of using such solvents lies in their high boiling point (203 °C and 164 °C

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• cross-coupling reactions Homogeneous green protocols Tsai et al. discussed an efficient, simple and environmentally friendly method for the coupling of arylynols 3 with an aryl halide [21]. This strategy discloses a one pot reaction catalyzed by FeCl3 in an aqueous medium associated with the cationic

• recovered by applying an external magnet and reused for successive five runs. Functional groups including nitro, carbonyl, and methoxy on the aryl halide were compatible with the catalyst. Aryl iodides gave better yields when compared to aryl bromides. A good synergistic effect of the nanoparticles with the

• yield was obtained when PdCoNPs/3DG was used with PPh3 as ligand and K2CO3 as base in water at 80 °C for 8 h. The reaction exhibited a high selectivity and the catalyst could be reused for at least seven cycles. Xu et al. analyzed a facile method for the coupling reaction of aryl halide and

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• proposed mechanism is shown in Scheme 15. Under blue visible light, the haloalkane is reduced by the copper acetylide to form the alkyl radical intermediate R2•. If aryl halide is the haloalkane, the copper acetylide is attacked by the aryl halide to form transition-state intermediate A. The copper

• acetylide is transformed into a high-valent CuIII complex, which subsequently undergoes reductive elimination or dissociation of the transition-state intermediate in the case of aryl halide to generate the target product (Scheme 15). From 2015 to 2020, Hwang and co-workers [67][68][69][70][71] investigated

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• the EDA complex formed by aryl halide 106 and oxindole 107 under alkaline conditions allowed single-electron transfer under irradiation with light, eventually affording arylated oxidized indole product 108 (Scheme 37). This reaction provides an effective method to construct various 3-arylindoles with

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• reported herein different methods for their synthesis. 1.1. Negishi cross coupling of aryl halide and organozinc compounds Jackson and co-workers reported the synthesis of a range of phenylalanine derivatives via Negishi cross-coupling reactions of aryl halides and Zn homoenolates of the protected (R

• involved a Negishi cross coupling of an aryl halide and the Zn homoenolate of the protected (R)-iodoalanine 2 using a Pd(0) catalyst. This method provided a versatile range of fluorinated phenylalanine products with high enantioselectivities and in acceptable yields. 2. Synthesis of β-fluorophenylalanines

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• and 2e were obtained in moderate yield using 3a as the aryl halide in the Heck reaction. The use of 3b in the Heck reaction resulted in a substantial improvement of yield in the synthesis of 2g but not for 2c. Interchanging the roles by using 5-vinylnicotinamide (5a) or methyl 5-vinylnicotinate (5b

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• probably deprotonation of the heterocyclic rings with a base. Moreover, nucleophilic aromatic substitution (SNAr) reactions between an aryl halide and a selenium reagent such as aryl selenide anion or diaryl diselenide for C(Ar)–Se bond formation using a base have been reported [20][21][22]. However, the

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• under microwave irradiation or thermal heating. The solvent was selected on the basis of literature data reported for other Pd-catalyzed reactions of estrone derivatives [18][20]. The pre-stirring of the reaction mixture without adding the aryl halide 1 was carried out at 60 °C for 5 min in a water bath

• , then aryl halide 1 was added and the mixture was irradiated in a microwave reactor at 150 °C for 10 min. The outcome of the couplings greatly depended on the nature of the Pd source, the ligand and the base. As summarized in Table 1, reactions with pre-catalyst Pd(OAc)2 gave the desired aminoestrone 5

• in low to high yields (Table 1, entries 1, 2, 4, 7–9) except when using Cs2CO3 as the base (Table 1, entries 6 and 10). In the latter cases only dehalogenation of the starting aryl halide was observed in around 20–60% yield. The use of KOt-Bu (Table 1, entries 2 and 8) or NaOt-Bu (Table 1, entries 4

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• donating as well as electron withdrawing functional groups, as coupling partners (Scheme 1). Concerning the targeted synthesis of 1, aryl halide 4e was of special interest as the cyano group is known to be convertible to the ortho-tetrazole moiety [9] present in the API. Based on prior optimisation studies

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• photoexcited state of [IrIII] to [IrII] and forms a thiyl radical. Next, the [IrIII] is regenerated by single-electron reduction of the aryl halide, delivering an aryl halide radical anion. Radical addition to the aromatic thiolate anion forms a sulfide radical anion intermediate, which is oxidized by the

• base and DMSO as solvent they observed a colouring of the reaction mixture, whereas the reagents are colourless themselves. They suggest that the thiol becomes deprotonated to the respective thiolate anion and subsequently an electron donor–acceptor complex with the aryl halide is formed. Irradiation

• with white light then triggers a light-induced electron transfer from the anion to the aryl halide, releasing the halide as an anion and resulting in a thiyl radical and an aryl radical. Finally, radical–radical cross-coupling yields the respective diaryl sulfide. Ammonium thiocyanate Formation of

Comparative profiling of well-defined copper reagents and precursors for the trifluoromethylation of aryl iodides

• Peter T. Kaplan,
• Jessica A. Lloyd,
• Mason T. Chin and
• David A. Vicic

Beilstein J. Org. Chem. 2017, 13, 2297–2303, doi:10.3762/bjoc.13.225

• -fold excess of aryl halide [4]. Therefore, while yields of the SIMes-based systems can provide good yields of product, the phen-based systems remain far more practical. Ligandless CuCF3 was also tested under the reported optimized reaction conditions [15], but in our hands the protocol afforded CHCF3

• reactivity of A2 for the more electron-rich aryl halide. Moreover, an induction period was observed for both A1 and A2. We noted a detection limit of approximately 2% with our NMR spectrometer, so we believe this induction period with the electron-rich substrates is real and not stemming from the different

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• -free Wittig reaction of organic halides with aldehydes or ketones (Scheme 6) [55]. Suzuki Coupling In 2000, Peters and co-workers first reported the palladium-catalyzed Suzuki coupling reaction under ball-milling conditions [56]. In a planetary mill for 30–60 min, the mixture of aryl halide (1.0 equiv

• ]. Mechanochemical Pd-catalyzed C–H activation [185]. Mechanochemical Csp2–H bond amidation using Rh catalyst. Mechanochemical synthesis of indoles using Rh catalyst [187]. Mizoroki–Heck reaction of aminoacrylates with aryl halide in a ball-mill [58]. IBX under mechanomilling conditions [8]. Thiocarbamoylation of

Ni nanoparticles on RGO as reusable heterogeneous catalyst: effect of Ni particle size and intermediate composite structures in C–S cross-coupling reaction

• Debasish Sengupta,
• Koushik Bhowmik,
• Goutam De and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 1796–1806, doi:10.3762/bjoc.13.174

• with comparable conversions (Table 1, entry 15). We then extended the optimized reaction conditions (as in Table 1, entry 4) using Ni/RGO-40 to diverse functionalized aryl halide/thiol combinations. The results are indeed encouraging and summarized in Table 2. Both coupling partners, i.e., the

• ) species, which then undergoes oxidative addition to the aryl halide forming a Ni(III) species, as proposed previously [19]. Conclusion In conclusion, we have shown that a RGO-supported Ni(0) nanocomposite (Ni/RGO-40) with average size (≈11–12 nm) Ni NPs display high catalytic efficiency for C–S cross

• /RGO-40 A mixture of aryl halide (1 mmol), thiol (1.2 mmol), potassium carbonate (1.2 mmol), Ni/RGO-40 catalyst (22 mg; Ni content is 8.8 mg, 0.15 mmol, 15 mol %) in DMF (3 mL) were taken in a 15 mL sealed tube, flashed and filled with N2 gas and quickly screw-capped. The reaction mixture was then