Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• cyanating reagents, such as p-toluenesulfonyl cyanide (TsCN) and N-cyano-N-phenyl-p-toluenesulfonamide [29]. The hydroboration of allenes with 9-BBN (9-borabicyclo[3.3.1]nonane) as the hydride source, followed by regioselective cyanation with allylic boranes, provided nitrile-substituted quaternary carbon

• scope for the formal hydrocyanation with 1,1-disubstituted and 1,1,3-trisubstituted allenes was examined (Scheme 3). All reactions were performed in the presence of 5 mol % IPrCuCl to generate the allylaluminum reagents in situ, followed by cyanation at room temperature for 30 min. This method

• , ethyl, phenethyl, and allyl groups, also underwent smooth cyanation, resulting in α-quaternary nitriles 3f–i in yields of 85–94%. Furthermore, aryl-substituted allenes 1j–o, incorporating electron-donating or electron-withdrawing substituents such as methyl, fluoro, chloro, bromo, trifluoromethyl, or

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• to give 22. In a same manner, Opatz et al. have shown that zinc phthalocyanins can catalyze oxidative cyanation reactions of tertiary amines 23, yielding α-aminonitriles 24 under continuous-flow conditions [36]. This reaction proceeds through the excitation of zinc phthalocyanin by near-infrared

• form the desired α-aminonitrile (Scheme 8). Notably, the authors have optimized the reaction conditions to achieve high yields across a wide substrate scope with more than 15 examples, including the cyanation of aliphatic amines such as tributylamine and sterically hindered substrates, which

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• ][22][23][24]. Moreover, copper-catalyzed asymmetric radical cross-coupling has advanced significantly over the past decade [25][26][27], with notable examples including Liu and Stahl’s enantioselective cyanation of benzylic C–H bonds using a Cu/chiral bisoxazoline catalyst [28], along with the Peters

• 2022, Xu and co-workers established a site- and enantioselective cyanation of benzylic C(sp³)–H bonds using an electro-photochemical strategy (Figure 7) [55]. The reaction conditions show a broad substrate tolerance, and the late-stage functionalization of complex molecules derived from natural

• cyanation of benzylic C(sp3)–H bonds (Figure 7) [56]. A wide range of electron-poor and electron-rich alkylarenes 20 are suitable substrates for this electrophotocatalytic radical relay strategy. Additionally, late-stage functionalization of bioactive molecules provides the corresponding chiral cyanation

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

• Selectfluor reagent abstracts a hydrogen atom from the substrate, which can then undergo further fluorination. The nitrate additive proved helpful as an initiator but is not necessary for certain substrates like sclareolide and protected ʟ-valine (Scheme 26). An electrochemical C(sp3)–H cyanation for LSF was

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• available in the absence of Lewis acid activation (Scheme 1a) [11][12]. A variety of Lewis acid activators have been reported [13][14][15][16][17][18][19][20][21][22] in an array of group-transfer reactions, including trifluoromethylation, cyanation, and fluorination. Brønsted acid activation has also been

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

• chemo-enzymatic total synthesis of jorunnamycin A (103). SfmC-catalyzed enzymatic conversion followed by cyanation and N-methylation also converted substrate analog 101 to the corresponding pentacyclic tertiary amine 102 in 18% overall yield based on peptidyl aldehyde 101. Subsequent simple chemical

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

• .20.133 Abstract We report a practical and sustainable electrophotochemical metal-catalyzed protocol for decarboxylative cyanation of simple aliphatic carboxylic acids. This environmentally friendly method features easy availability of substrates, broad functional group compatibility, and directly

• ][18]. Owing to the prevalence of aliphatic carboxylic acids in biomass and natural products, decarboxylative cyanation represents one of the most straightforward and attractive approaches to accessing alkylnitriles [19][20]. As an elegant example, Barton demonstrated the application of redox-active

• esters, the so called "Barton esters", for decarboxylative cyanation of aliphatic acids with tosyl cyanide as the nitrile source under visible light irradiation at room temperature [21][22]. Although two synthetic steps are required, this is the first practical decarboxylative cyanation protocol because

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

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

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• -indoline and gave the Bpin-N-indoline product 27; this was suggested as the major pathway (Scheme 7). Thomas et al. reported the H-B-9-BBN-catalysed reductive cyanation of enones with HBpin and N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) (Scheme 8) [71]. The reaction was proposed to proceed by 1,4

• -hydroboration of the enone 29 with H-B-9-BBN to give an O-B-9-BBN enolate 30. Electrophilic cyanation of the enolate 30 with NCTS 31, and elimination gave the β-ketonitrile 33 and TsN(Ph)-9-B-BBN 34, which underwent B‒N/B‒H transborylation with HBpin to regenerate the catalyst and give TsN(Ph)-Bpin 35 (Scheme 8

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• conditions the oxidative ABNO-catalyzed α-cyanation of amines was realized with no need for N-protecting groups [105] (Scheme 16B). The key reactive species proposed in these electrochemical reactions are the oxoammonium cations formed from the amine-N-oxyl catalyst at the anode. The oxoammonium cation

• electrochemical oxidation of primary alcohols and aldehydes to carboxylic acids. Electrocatalytic oxidation of benzylic alcohols by a TEMPO derivative immobilized on a graphite anode by π–π stacking interactions. Electrochemical oxidation of carbamates of cyclic amines to lactams and oxidative cyanation of amines

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• transborylation (a σ-bond metathesis turnover method) has been used for borane-catalysed reductions of N-heteroarenes [28][29], and the borane-catalysed cyanation of enones [30]. Applying B–N/B–H transborylation to the hydroboration of nitriles would enable the development of a borane-catalysed hydroboration of

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• cyanation of the resulted isoxazoles 8a–f to cyanides 9a–f using Me2C(OH)CN/(Me2N)2C=NH [29], their acid hydrolysis, followed by esterification of the resulting acids 9a–f with diazomethane. 4-Iodoisoxazoles 12a–f, necessary for the preparation of 3,4-disubstituted isoxazoles, were obtained by iodination of

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• Thaipparambil Aneeja Cheriya Mukkolakkal Abdulla Afsina Padinjare Veetil Saranya Gopinathan Anilkumar School of Chemical Sciences, Mahatma Gandhi University, PD Hills, Kottayam, Kerala, 686560, India 10.3762/bjoc.18.4 Abstract The cyanation reaction has achieved rapid progress in recent times

• . The ability to exhibit multiple oxidation states increased the demand of ruthenium in the field of catalysis. These cyanation reactions have wide application in pharmacological and biological fields. This review gives an overview of the ruthenium-catalyzed cyanation reactions covering literature up to

• 2021. Keywords: cyanation; nitriles; photocatalyst; ruthenium; tertiary amines; Introduction Nitriles are a major class of organic compounds having wide significance in materials science, agrochemical and pharmaceutical industry [1]. They are the privileged compounds finding broad applications in

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• approaches for the trifluoromethylthio (SCF3) difunctionalization of alkenes, such as cyanation [23], etherification [24][25][26][27], amination [28][29][30], chlorination [31][32], hydrogenation [33], trifluoromethylation [34], phosphonization [35], arylation [36][37][38], trifluoromethylthiolation [39

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• nitrones (products 150a–d). A similar cyanation reaction was realized using TMSCN as a cyanide source and the oxidative system Cu(NO3)2/K2S2O8 (Scheme 51) [140]. Both aromatic (products 152a–c) and aliphatic (products 152d–f) β,γ-unsaturated oximes undergo this transformation. Oximes substituted at the α

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

• product 2-[18F]FPhe 46 in 43% yield, whereas under microwave irradiation a 34% yield was obtained. Under the optimized conditions, the enantiomeric purity was reported to be ≥94% ee [46] (Scheme 10). 1.3. Photooxidative cyanation of fluorinated benzylamine A convenient, protecting group-free, and

• semicontinuous process was reported for the synthesis of racemic fluorinated phenylalanine·HCl starting from benzylamines 47a–c. Thus, a singlet oxygen-driven photooxidative cyanation of amines 47a–c using tetraphenylporphyrin (Tpp), followed by an acid-mediated hydrolysis of the intermediate fluorinated α-amino

• photooxidative cyanation. Synthesis of FPhe derivatives via Erlenmeyer azalactone synthesis. Synthesis of (R)- and (S)-2,5-difluoro Phe via the azalactone method. Synthesis of 3-bromo-4-fluoro-(S)-Phe (65). Synthesis of [18F]FPhe via radiofluorination of phenylalanine with [18F]F2 or [18F]AcOF. Synthesis of 4

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• -derived benzylic copper species with an electrophilic source of a cyano residue, Yang and co-workers reported on the Cu-catalyzed borylation of styrenes bearing an allylic group at the 1-position. After the initial addition, a cascade of reactions occurred, including cyanation generating a dearomatized

• steps: first, borocupration followed by an electrophilic cyanation, and finally, a second borocupration. It was discovered that steric factors determine the site of the first borocupration, while electronic effects are dominant in the second addition of boron (Scheme 61) [114]. The selective

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• the reported procedures. This being the case, in 2013, Itoh and co-workers reported the C–H perfluoroalkylation with photoredox catalyst 7 (Scheme 28), and they obtained the best yields with electron-rich arenes compared to electron-deficient ones [180]. C–H cyanation: synthesis of benzonitrile

• using the efficient photoredox catalyst 3a at room temperature [181]. The reaction was compatible with the presence of electron-donating as well as electron-withdrawing groups, with TMSCN as an ideal cyanation reagent (Scheme 29). In the absence of light or a photocatalyst, no product was obtained. A

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• analyses. Compound 4 is the product of dehalogenation reaction, which is known to be catalyzed by palladium [1][18]. The second side product, compound 5, is probably the result of the cleavage of the C–CN bond in the solvent (propionitrile or acetonitrile), followed by a palladium-catalyzed cyanation of

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• catalytic hydrogenation to 4 followed by protection with TBDMS to give 5 in 63% yield for three steps. The synthesis of the other half of the photochrome started with bromination of difluorinated aniline to give 6 followed by copper-catalyzed cyanation to 7 in 62% overall yield. Diazonization of 7 with

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264