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

• corresponding arylated N-acetyl diazocines 7, and 9–13 in yields from 68 to 88% (Table 4). The yields increased slightly if boronic acids with electron-withdrawing groups were used. An influence of bulky substituents like carboxyl groups in ortho-position of the phenylboronic acids on the reaction was not

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

• oxidize boronic acids such as 47, producing the corresponding alcohols 48 via a single-electron-transfer mechanism that leverages atmospheric oxygen (Scheme 13). While the initial photocatalytic results using NIR-irradiated 46 were promising, the overall reaction kinetics were relatively slow. In response

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

• synthetic methodology for N-arylamides 13 from dioxazolones 11 and boronic acids 12 using copper salts (Scheme 5) [90]. As illustrated, dioxazolones with both electron-rich and electron-poor substituents, including alkyl substituents, were well-tolerated, providing the desired products 13a–h. However, the

• substrate scope of boronic acids was limited in this transformation. To elucidate the reaction process, kinetic and control experiments were conducted, which led to the proposed reaction pathway for the copper-mediated synthesis of N-arylamides from dioxazolones as shown in Figure 4. Initially, copper(I

• ) chloride reacts with boronic acids, forming the copper aryl complex INT-16, which then undergoes decarboxylative N–O bond insertion to generate the copper nitrenoid intermediate INT-17. Thereafter, nitrene insertion into the copper–carbon bond occurs, forming a new C(sp2)–N bond (INT-18). Finally, the

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

• primary anilines using a copper catalyst and dual Cu-electrode system to form C–N bonds (Figure 19) [79]. This catalytic system demonstrates a broad substrate scope, including electron-deficient boronic acids, which are typically regarded as challenging substrates because of their low reactivity in Chan

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• literature procedure [35]. With initial success in the synthesis porphyrin 26, this Suzuki coupling reaction was performed on 13, for a range of boronic acids/esters as shown in Figure 2 and Scheme 2. Boronic acids/esters were chosen based on their electronic properties (activating/deactivating) as well as

• ). The reaction temperature was increased to 110 °C, affording the desired porphyrin 27 in a 39% yield (Table 1, entry 3). A temperature of 110 °C was also used for the synthesis of terphenylporphyrin 28 using boronic acid 17, affording terphenylporphyrin 28 in 48% yield (Table 1, entry 7). Boronic acids

• stability than boronic acids and other employed esters as the four methyl groups protect the boron center from attack of water [44][45], preventing protodeboronation from the hydrolysis route. However, protodeboronation can be complex when it comes to pKa considerations, for example, 3,5

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• investigated using various boronic acids 4 and alkynes 5 in cross-coupling reactions using 1 (Table 3 and Table 4). p-Tolylboronic acid 4b provided 2b quantitatively, whereas m- and o-tolylboronic acids 4c and 4d produced 2c and 2d in low yields because the methyl group was positioned near the reaction site

• (Table 3, entries 1–3). Introduction of 3,4-methylenedioxyphenyl (4e) or p-fluorophenyl groups (4f) to 1a proceeded in high yields (Table 3, entries 4 and 5). Boronic acids with carbonyl groups such as acetyl, ester or formyl moieties in para position (4g–i) underwent the cross-coupling in 76, 96 or 77

• and various boronic acids 4. Cross-coupling reactions between multihalogenated vinyl ethers 1 and various alkynes 5. Supporting Information Supporting Information File 16: Characterization data for 2b–s and 3b–w, and copies of 1H, 13C, and 19F NMR spectra.

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• 24, which supported the hypotheses regarding the selectivity-determining transition states arrangement. It is important to note, that boronic acids 14 are highly sensitive to oxidation by air and could only be purified in air-free conditions and stored in airtight containers. Additionally

• , prenylboronic acid (R = H) was synthesised in only 31% yield. Given the 1.5 equiv loading of the boronic acids in the allylation protocol, the overall atom economy is not ideal. Asymmetric allylation of in situ-formed imines catalysed by chiral BINOLs received further development in the work of Schaus [26]. The

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• phase transfer catalyst and an arylboronic acid [97] (Figure 7). After a systematic data set design involving eight phosphoric acids and eight boronic acids, the authors observed breaks in linearity of the model of enantioinduction for some catalyst combinations. Further experiments, such as non-linear

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

• -unsaturated ketones 98 are S,S-ketene acetals capable of undergoing Liebeskind–Srogl coupling with boronic acids and phenylhydrazine in a consecutive three-component reaction to give pyrazoles 99 (Scheme 35) [118]. Beltrán-Rodil et al. used a similar strategy to synthesize 1,3,5-substituted pyrazoles 101 by

• Suzuki coupling of β,β-dibromenones 100, boronic acids, and 1,1-dimethylhydrazine in a three-component reaction (Scheme 36) [119]. The intermediary 5-bromopyrazoles formed by condensation/N-demethylation/cyclization sequence subsequently react by Suzuki–Miyaura cross-coupling in a one-pot fashion. The

• arylhydrazines 116 are used as starting materials. The p-bromophenylpyrazoles presented in situ can be reacted with boronic acids or boronic acid esters in a sequentially Pd-catalyzed coupling towards biaryl-substituted pyrazoles 113, 115, and 117 (Scheme 41) [138]. Furthermore, a pseudo-five-component reaction

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• temperature and then, upon addition of the boronic acid, heating at 60 °C (Scheme 9). Similar efficiencies were observed with a wide range of boronic acids (10 examples, 49–87% yield). The biohybrid was suitable also for gram-scale synthesis and for storage at room temperature under inert atmosphere, showing

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• strategy is founded on the build and release of molecular strain and achieves a formal transposition of a methyl group. During light irradiation, 3-phenylazetidinols are forged as reaction intermediates, which readily undergo ring opening upon the addition of electron-deficient ketones or boronic acids

• subsequent ring-opening reactions. In this regard, we uncovered a novel entry to dioxolanes by intramolecular ring opening of azetidines using ketones and boronic acids. Results and Discussion Photocyclization We initiated our study by a systematic investigating of the Norrish–Yang cyclization for the

• . Dioxolanes 11 and 16 are inherently stable and we were unable to cleave the ketal after reaction. Thus, we investigated the feasibility to use boronic acids in the ring-opening reaction (Scheme 3c). Phenylboronic acid 17 is known to exhibit a similar acidity as the corresponding hemiketals providing a

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

• recently, Zhao and co-workers published a novel synthesis of indole-3-yl aryl ketones by a Pd-catalyzed direct carbonylation of the corresponding indoles with boronic acids [73]. The best catalyst was Pd(OAc)2 which catalyzed the reaction well in the presence of a base, such as KOH, in toluene as solvent

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

Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones

• Ksenia Malkova,
• Andrey Bubyrev,
• Stanislav Kalinin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60

• modification of various substrates, such as 3-bromoquinolines [52][53][54][55], quinoline-3-boronic acids [56], and diazonium salts [57]. When considering general methods for the quinoline core formation, aromatic ortho-substituted carbonyl compounds attract attention as decent and easily available reagents

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• . However, depending on the nature/substitution pattern of the arylboronic acid, some of the arylglycine products could only be obtained in very low enantioselectivities. This can be attributed to a fast, uncatalyzed racemic background reaction of the boronic acids, in particular for electron-rich or

• to our previous study with the corresponding boronic acids [22]). Synthesis of both enantiomers of arylglycine building block 18. Reaction optimization. Supporting Information Supporting Information File 176: Experimental section and characterization data. Funding Financial support by the research

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

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

•  1b) [21][22][23]. In particular, N,N,N-trihydroxy-TAAD derivatives (3O-TAADs) were shown to be chelating ligands for boron [24]. The application of TAAD-boronate complexes was demonstrated by the preparation of conjugates of boronic acids with biomolecules [25][26], COF-like materials [25], and

• dynamic covalent libraries [25]. TAAD can be covalently bound to a polymer matrix through the nucleophilic nitrogen N(1) that was used to prepare scavengers of boronic acids [25]. Also, TAAD was demonstrated to serve as a scorpionate-type ligand for manganese and iron leading to complexes with the metal

• TAADs are able to serve as chelating ligands. In recent years, cyclic boron ate-complexes have received much interest as protected forms of boronic acids [37][38][39]. From this experiment, it became apparent that TAAD derivatives bearing free N-amino groups are prone to cage opening. To stabilize the

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• inductive heating technology has also been used in multistep processes targeting drugs or important molecules in the fragrance industry. The first example deals with a metal-free carbon–carbon-bond formation process between tosylhydrazones generated from the corresponding aldehydes 74 and boronic acids 76

• protocol began with the carbonyl compounds (e.g., 74), and the first flow step yielding tosylhydrazones that were transferred directly to the second reactor to be coupled with boronic acids (Scheme 13). Both steps required heating, which was performed by electromagnetic induction of a fixed-bed material

• fixed-bed materials serving as catalysts: A. with copper metal, B. with Au-doped MagSilicaTM, and C. with Pd-doped MagSilicaTM. Two step flow protocol for the preparation of 1,1'-diarylalkanes 77 from ketones and aldehydes 74, respectively, and boronic acids 76. O-Alkylation, the last step in the

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• equiv; 1 equiv in case of meta-substituted boronic acids), copper(I) 3-methylsalicylate (2.2 equiv), dioxane, 130 °C, 4 h, argon; iii – oxone (2.5 equiv), DMF, 80 °C, 3 h; iv – NaCN (2.2 equiv), THF, reflux, 3.5 h; v – 4-t-BuC6H4SH (1.1 equiv), Et3N (1.1 equiv), THF, 50 °C, overnight, argon. DFT

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• -butanesulfinyl ketimine; homocoupling; Introduction As bioisosteres of carboxylic acid derivatives, boronic acids have recently emerged as a novel chemotype in drug design, with a number of boron-containing compounds recently being approved by the FDA [1][2][3][4]. In particular, α- and β-aminoboronic acids are

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• halotryptophans and boronic acids resulting in RGD peptides with high affinity towards integrin αVβ3, good selectivity and high plasma stability [72]. Results and Discussion Design and synthesis of SMC stapled peptides The intramolecular SMC was envisaged as a novel approach towards one-component peptide stapling

A photochemical C=C cleavage process: toward access to backbone N-formyl peptides

• Haopei Wang and
• Zachary T. Ball

Beilstein J. Org. Chem. 2021, 17, 2932–2938, doi:10.3762/bjoc.17.202

• residue (Figure 1C, step, i + iv → ii) [18][19][20]. Subsequent investigations validated the use of photoreactive boronic acids as an approach to reversible backbone N–H modification via photocleavage of an alkenyl C–N bond [16][17]. Traditional 2-nitroaryl groups allow cleavage of benzylic C–X bonds (e.g

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

• , Xiao and Yu et al. [61][62] disclosed a series of copper-catalyzed cyanoalkylation reactions among alkenes, oxime esters, and boronic acids or alkynes. Mechanistic studies implied that the CuI complex gets photoexcited via a SET process to generate a cyanoalkyl radical from the oxime esters. The

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• Petasis three-component reaction followed by the Pomeranz–Fritsch–Bobbitt cyclization. The Petasis reaction between boronic acids, carbonyl derivatives, and amines, leading to the formation of amino acids and the Pomeranz–Fritsch–Bobbitt cyclization of amino acetals, leading to the construction of C-1

• yields of 85–99% as indicated in Scheme 3. The aminoacetals 3a–e were suitable for use directly in the next step of the synthesis without further purification. Then, the N-benzylated aminoacetals 3a–e were subjected to the Petasis reaction with glyoxylic acid hydrate (4) and the appropriate boronic acids

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• –Miyaura cross-coupling reaction of a variety of halogenated methoxybenzene-containing compounds with 2-(formylphenyl)boronic acids in generally good yields [15]. As a next step, the biaryl aldehydes 13a–f were converted into their corresponding oximes 14a–f in good yields as a mixture of (E) and (Z