Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• amination is a versatile and powerful tool for C–N bond formation and widely applied in the synthesis of new pharmaceutical substances [29][30][31]. Furthermore, azobenzenes [32][33], as well as diazocines [34][35], have been derivatized via Buchwald–Hartwig amination. The Buchwald–Hartwig amination of

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• potential bioactivity [70][71][72][73]. Despite the development of synthetic approaches for six-membered lactams, including transition-metal-catalyzed transformations, several limitations remain, particularly with regard to regioselectivity and asymmetric C–N bond formation, which are still limited. In 2023

• , the Chang group elegantly unveiled a protocol for an enantioselective C–N bond formation, introducing δ-lactams from dioxazolones using a copper(I) catalyst and a chiral BOX ligand [74]. As shown in Scheme 2, dioxazolones containing aryl and heteroaryl groups were converted into the corresponding

• nitrenoid intermediate was characterized by the same group [75]. Further radical rebound from INT-4 induces the enantioselective C–N bond formation. Finally, the desired product 2 is released from INT-4, regenerating the active chiral copper species to participate in the catalytic cycle. 1.2 C(sp2)–H

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

• the product are accessible by adjusting the two distinct chiral catalysts. C–N Bond formation In 2018, Mei et al. developed the electrochemical C–H amination of arenes with amine electrophiles using copper catalysis, which provided a step-economical approach for the synthesis of aromatic amines by

• undergoes reductive elimination to provide the desired enantioenriched nitrile product 111 and Cu(I) catalyst 116. The resulting Cu(I) catalyst 116 is reoxidized to Cu(II) 117 at the anode, completing the catalytic cycle. Coupling reaction (Chan–Lam coupling) Transition metal-catalyzed C–N bond formation

• boronic acid and disproportionation. Subsequently, the coupling product 120 is released through reductive elimination, and the resulting Cu(I) species 121 is either reoxidized or plated on the cathode. Despite the success of electrochemical Chan–Lam coupling for C–N bond formation, the electrooxidative

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• the mechanism is the attack of the protonated pyridin-2-one to the copper-complex of the enamine XXXII resulting from the reaction between acetophenone and O-tosylhydroxylamine, which occurs with elimination of TsOH. The so-obtained imino–copper complex XXXIII gives rise to an intramolecular C–N bond

• formation releasing Cu(OTf)2. The final bicyclic product 33 arises from isomerization and water elimination. Recently, Singh's research group developed a cascade process to access imidazo[1,2-a]pyridines-linked isoxazoles 35. Isoxazole carbaldehydes treated with 2-aminopyridines and isonitriles in the

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• regardless of the electronic properties of the substituents on the N-phenyl ring. When dissymmetric diaryl ketone-derived substrates were employed, the C–N bond formation occurred selectively on the most electron rich aromatic ring. According to the proposed mechanism, this dehydrogenative cyclization of

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• reactions allow the sustainable construction of C–C and C–N bonds using alcohols as hydrogen donors. In recent years, manganese complexes have been explored as efficient catalysts in these reactions. This review highlights the significant progress made in manganese-catalyzed C–C and C–N bond-formation

• compounds. To achieve the selective C–C and C–N bond formation via hydrogen borrowing, controlling the selectivity is an important factor since the formation of possible side-products such as overreduction of unsaturated compounds or dialkylation. Hence, developing an efficient catalyst, capable of

• several reviews have been reported on their applications in dehydrogenative coupling reactions [21][22][23][24]. This review focuses mainly on the BH reaction to create sustainable C–C and C–N bonds with manganese catalysts. Review C–N bond formation with alcohols and amines Amines and their derivatives

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• review in 2018 focused on a variety of routes to these compounds [8]. The well-known Buchwald–Hartwig (B–H) and Chan–Lam (C–L) reactions have proven to be highly useful procedures that allow the step-economical synthesis of diverse biologically relevant heterocycles through C–N bond formation [9]. These

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• under heating, followed by the formation of ylide, N–S bond cleavage, and C–N bond formation along with the release of N2. In 2019, Sun and co-workers introduced an unprecedented method for the synthesis of isothiourea derivatives via the activation of diaryl/alkyl disulfides 47 with N-halosuccinimides

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• electron-withdrawing groups on the aryl ring reacted smoothly with iodonium ylides to give the corresponding diarylamines with good to excellent yields. Also, secondary amines underwent N-arylation to deliver tertiary amines with moderate yields. Keywords: amines; arylation; C–N bond formation; iodonium

• strategies for C–N bond formation have been extensively explored by various research groups for the N-arylation of amines. Specifically, seminal contributions by Buchwald [15] and Hartwig [16] involving the use of palladium complexes as catalysts in the presence of either phosphine or diamine ligands for C–N

• bond formation. However, these methods suffer from limitations such as moisture sensitivity, the requirement of specific ligands, and the use of expensive palladium catalysts [17]. Also, Chan Lam, Evans, and other research groups have developed copper-catalyzed C–N bond formation reactions by careful

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

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• for the synthesis of 1,2-azaphospholidine 2-oxides/sulfides and their fused derivatives. The 1,2-azaphospholidine 2-oxide/sulfide derivatives have been prepared by construction of any of their ring bonds. Synthesis via C–N bond formation In 1962, Helferich and Curtius reported the first synthesis of a

• 1,2-azaphospholidine 2-oxide (γ-phosphonolactam) from N,N’-diphenyl 3-chloropropylphosphondiamide (1), which was cyclized to 1-phenyl-2-phenylamino-γ-phosphonolactam (2) in the presence of NaOH in methanol via the C–N bond formation (Scheme 1) [21]. In 1974, the strategy was applied for the synthesis

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• ). Enantioselectivity for a wide range of substrates was achieved in good yield with rigorous optimization of the reaction conditions by utilization of wild-type CAL-B. Synthetic N-glycosylation strategies for glycosidic C–N bond formation in 1,3-oxathiolane nucleosides This section will discuss the methods for

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

• extending this protocol from C–N bond formation reactions to C–O [85], C–S [86], and C–C [87][88] bond formations. Recently, a photoredox catalysis was applied to these types of cross-coupling reactions, with key contributions from the groups of Ackermann [87], Evano [55], Zhang [89], Nguyen [90], and

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

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• -alkenyloxindole 43 were considered to be the building blocks united in ethanol as solvent (Scheme 15). The notable highlights of the described methodology are diastereoselective C–C and C–N bond formation, high yields, non-toxic product, and cost-effectiveness along with a greener approach. The synthetic strategy

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• quinazolinones [30][31] and taking into consideration the biological importance of aminophthalazine derivatives, we decided to apply the methodology based on the palladium-catalyzed C–N-bond formation (Buchwald–Hartwig-type reaction) as a convenient and effective approach for the synthesis of the new

• course of the reaction and in several cases resulted in the formation of 2-methylphthalazin-1(2H)-one, i.e., the debromination product of bromophthalazinone 3a. The commonly adopted view on the mechanism of the Pd-mediated C–N-bond formation (Buchwald–Hartwig-type coupling) [37][38][39][40] assumes that

Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

• Geetanjali S. Sontakke,
• Rahul K. Shukla and
• Chandra M. R. Volla

Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42

• significant interest in the last few years [12][13]. In particular, the C2-functionalization of quinolines has been well studied, and various methodologies were established for C–C [14][15][16][17][18][19][20][21][22][23], C–O [24][25] and C–S [26][27] bond formation. Recently C2-selective C–N bond formation

• purified by column chromatography (ethyl acetate/petroleum ether 1:9) to get the desired product 3a in 92% yield (50 mg, 0.18 mmol). Bioactive molecules containing the 2-aminoquinoline motif. C2-selective C–N bond formation of N-oxides. Substrate scope of N-sulfonyl-1,2,3-triazoles. Reaction conditions: 1a

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• endpoint. However, Nicolaou’s route is the shortest (6 or 7 steps, 9.8–9.2% yield), while Kitahara’s synthesis is the highest-yielding and does not involve the use of expensive transition metals or organocatalysts. Syntheses to generate the C-14 stereocenter via C–N bond formation Two groups implemented

• strategies that rely on the generation of the C-14 stereocenter by stereoselective C–N bond formation. The Jacobsen group utilized an asymmetric Cr(III)-catalyzed cycloaddition reaction [27] between (2Z,4E)-3-(triethylsilyloxy)-2,4-hexadiene (40) and the aldehyde 41 to generate the 4-silyloxydihydropyran 43

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• formed by an intramolecular C–C or C–N bond-formation event, as detailed in the following. 2.1 Synthesis of phenanthridines via photocatalyzed intramolecular C–C bond formation A typical approach makes use of imidoyl radicals [30][44] as the key intermediates. Among the different methods proposed to

• proximity to each other, prone to be engaged in a bidentate-type metal-coordination complex [75]. 2.2 Synthesis of phenanthridines via photocatalyzed C–N bond formation As mentioned in the introduction, the examples gathered here involve the intermediacy of N-centered radicals. As a representative case, the

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

• rule, a C–O bond is formed in intermolecular reactions, intramolecular cyclization generally occurs with the formation of a five-membered cycle of isoxazoline (C–O bond formation) or nitrone (C–N bond formation). Application of the oxime radicals in organic synthesis: intermolecular reactions Selective

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• selectivity. Homo- and cross-coupling adducts 16a and 16b–g were obtained from the corresponding phenols (14a–e and 15a–c) as shown in the bottom of Scheme 9 with high chemoselectivity. C–N bond formation While copper complexes are at the heart of oxidative biological networks, the introduction of nitrogen is

• metalloenzymatic active site was not characterized in detail, it might bear some resemblance to the original biological active site. Building on their previously discussed phenol oxidation methodology (Scheme 5 and Scheme 6), Lumb and co-workers have targeted subsequent C–N bond formation to access oxindoles [34

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• = Cu/Au molar ratio, Gx = dendrimer generation, and AAA = dendron type). After the preparation and characterization of the CuYAu–Gx-AAA–SBA-15 catalyst, the material was employed in a triazole synthesis, and it was established that the catalyst was efficient in the Sharpless–Meldal C–N bond formation

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• chlorodiphenylphosphine, afforded 1-methyl-4,5-bis(diphenylphosphino)imidazole (85). Finally, N-methylation gave the imidazolium salt derivative 86 in good yield (65%). Preparation of N-heterocyclic phosphines via metal-catalyzed P–C/N bond formation There is limited availability of certain N-containing precursors and

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• iodide (Table 3, entries 2–7). Under identical conditions, 2-iodothiophene, and iodopyridine derivatives could also easily be converted to the corresponding acetylene with good or even excellent isolated yields (3i–n). When 2-amino-3-iodopyridine (1i) was converted no C–N bond formation was detected