A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• for determining the absolute configurations of chiral alcohols [8][9][10][11][12][13][14], primary amines [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], secondary amines [33][34][35], carboxylic acids [36][37][38], sulfoxides [39], and cyanohydrins [40]. We have reported

• a m-quaterphenyl probe 1 to determine the absolute configurations of primary amines [41]. When compound 1 is linked to the amines, the information on the absolute configurations were transcribed into a twist of two biphenyl chromophores in the m-quarterphenyl group. From the sign of the Cotton

• effect in CD, the direction of twist can be estimated. The absolute configuration of amines can be determined by comparing the direction of the twist determined by CD with that obtained by conformational analysis using theoretical calculations. However, this method has only been applied to simple primary

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• higher than conventional aviation kerosene (0.78 g mL−1). Conversion of CPN to cyclopentylamines and alcohols: Gong and Wang revealed the potential of cobalt oxide catalysts for the production of primary amines via reductive amination of CPN (Scheme 68) [213]. CoO species with oxygen vacancies on the

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• experiments were carried out. During the substrate screening we noted that reaction between aldehydes and primary amines resulted in only traces of the product of reductive amination. In these reaction mixtures, exclusively Schiff bases were detected since they precipitated under neat conditions and left the

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• unsymmetrical diisocyanide was used, the initial isocyanide insertion was found to be non-regioselective, delivering a 1:1 mixture of regioisomers (17c and 17c’). Intriguingly, 17a could act as a chiral acylating reagent, applying in the kinetic resolution of racemic primary amines rac-18. Additionally, after

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• benzotriazole-adduct formation proceeds poorly with sterically demanding secondary amines and fails with primary amines. However, the latter may be overcome by adding a temporary benzyl group on the amine which can be subsequently cleaved by hydrogenolysis as demonstrated by the authors. Finally, it was shown

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• scaffold for aminations with 14 commercially available primary amines. Reacting scaffold 1 with excess primary amine at room temperature for 16 h generated the desired amine analogues in respectable yields (18–87%) and high purity (≥95%) following chromatography workup. The structures of the 14 previously

• -position of the pyrazine ring [10][11]. During small-scale late-stage functionalisation of natural products, we have observed that amination or amidation with primary amines often involves less of a kinetic barrier than might otherwise be expected [12][13][14]. The use of readily available liquid amines in

• triazolopyrazines from 5-halogen substituted triazolopyrazines and primary amines now in hand, 13 other commercially available liquid primary amines were employed for the synthesis of additional aminated triazolopyrazine analogues (Scheme 2). TLC analysis of the room temperature reaction with phenethylamine (as

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• ) triflate-catalyzed post-Ugi assembly of novel pyrazolo[1,5-a][1,4]diazepine scaffolds is reported offering high yields (up to 98%) under mild conditions. The synthetic sequence involves the Ugi four-component reaction (U4CR) of pyrazole-3-carbaldehydes, primary amines, 3-substituted propiolic acids, and

• employed the U4CR of ortho-halogenated benzaldehydes 7, primary amines 2, 3-substituted propiolic acids 8, and isocyanides 4 to synthesize propargylamides 9. These propargylic Ugi adducts 9 were subsequently subjected to a Cu-catalyzed tandem azide–alkyne cycloaddition/Ullmann coupling resulting in the

• account chemical and pharmacological importance of fused pyrazole derivatives [48][49][50][51][52][53], we herein report the post-Ugi assembly of novel pyrazolo[1,5-a][1,4]diazepine scaffolds 16 (Scheme 1d). The synthetic sequence involves an Ugi reaction of pyrazole-3-carbaldehydes 14, primary amines 2

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• ]. Kowalczyk and co-workers showed how asymmetric organocatalysis can benefit from mechanochemical activation. They established that Michael additions of thiomalonates to enones, catalyzed by cinchona-derived primary amines, is efficient and enantioselective under ball-milling conditions [24]. Kondratyev and

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• of chemoselectivity becomes important when formaldehyde is used. Moreover, primary amines (alkyl- and arylamines) can also react with two equivalents of both the formaldehyde and the P(O)H compound. In this case, a double Kabachnik–Fields condensation gives bis(phosphorylmethyl)amines 34 as possible

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• of primary amines was reacted with methyl cyanoacetate [46], giving rise to the corresponding cyanoacetamides 1 (Scheme 2). Subsequently, they were reacted accordingly to yield a variety of the targeted precursors, 2-aminothiophenes 2 [42], 2-aminoquinolines 3 [45] and 2-aminoindoles 4 [44], via

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

• reaction was also fruitful to obtain 1,2-dihydroisoquinolines 25 starting from 2-alkynylbenzaldehydes, primary amines and allylic or benzyl bromide, in the presence of zinc and using the combination of Mg(ClO4)2/Cu(OTf)2 as catalyst. The use of a mixture THF/DCE 1:20 as solvent was mandatory, because THF

• was crucial for the formation of the organozinc reagent (Scheme 19) [36]. Spiro-2,3-dihydroquinazolinones 26 were formed exploiting a one-pot multicomponent reaction, using isatoic anhydride, ketones and primary amines. The isolation of the amide intermediate XXIII obtained by the copper-catalyzed

• process by using α-diazoketones, nitroalkenes and primary amines, in the presence of air as oxidant. The mechanism involved the formation of α-ketocarbene XXVI from α-diazoketone, able to react with the amine affording imine XXV after copper-catalyzed oxidative dehydrogenation. The subsequent [3 + 2

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• :1 (Scheme 3, 3e). Carbonates with aryl or styryl residue can undergo the reaction smoothly (Scheme 3, 3f–k), but alkyl-substituted substrates showed low yields (Scheme 3, 3l and 3m). Moreover, secondary amines with various substituents, acyclic amines, primary amines, or even the amine moieties in

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• analogue, the DMP-tag, which in contrast to standardly used isotopic tags bearing the N-hydroxysuccinimide ester (NHS-ester) reacting with all primary amines of lysine side-chains, allows to selectively label the probe–protein conjugates (Figure 7A) [81][83]. The DMP-tag can be prepared in a six-steps

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• significant advancement in mechanocatalysis. The stereoselective addition of bisthiomalonates 1–4 to cyclic enones and 4-chlorobenzylideneacetone proceeds stereoselectively under iminium activation conditions secured by chiral primary amines, in contrast to oxo-esters as observed in dibenzyl malonate addition

• time of two days under a pressure of 0.8 GPa [23]. Less reactive benzyl malonates, which allow for the cleavage of a free carboxylic group without the need for harsh base- or acid-mediated conditions [24], undergo additions catalyzed by primary amines [19]. However, these transformations are hampered

• novel approach based on iminium catalysis employing chiral primary amines under ball milling conditions. Ball milling induces localized and transient temperature and pressure increases which could influence changes in the free activation volume [32][33][34], favoring Michael additions [35]. Furthermore

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

• in situ preparation of diazo compounds, as the substances are difficult to handle and toxic [170]. Approaches such as nitrogen transfer with tosylhydrazones, use of the Bestmann–Ohira reagent, or transformation of primary amines or azides, among others, represent viable and practical options. Diazo

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

• oxidation of N-arylhydrazone by electrogenerated iodide radical (Scheme 11) [50]. In parallel, the group of Yuan achieved the electrosynthesis of 1,3,5-trisubstituted 1,2,4-triazoles 67 from arylhydrazines 64, aldehydes 65 and primary amines 66. Iodine-mediated electrooxidation of in situ-generated aldehyde

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

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• bonds and primary amines of the amino acid chains are available for methylation, leading to poor site selectivity of any methylating reaction [39]. Therefore, either pre-methylated amino acids or short methylated peptides are incorporated into the full-length peptide. Direct O-methylation of an O

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• cyanoarenes is a straightforward and powerful method for the synthesis of primary amines [5], and the reduction of nitroarenes is useful for the synthesis of aniline derivatives [6][7][8][9][10][11]. Nitrogen-containing aliphatic heterocycles, such as piperidines and tetrahydroquinolines, are key motifs in

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• derivatives by means of nucleophilic azlactone-opening reactions. Gratifyingly primary amines can be easily utilized under reflux conditions to access the amide derivatives 6a and 6b straightforwardly (Scheme 3), thus demonstrating the versatility of compounds 5 to access more complex acyclic α-AA derivatives

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• additive-free synthesis of 2-benzyl N-substituted anilines from (E)-2-arylidene-3-cyclohexenones and primary amines has been reported. The reaction proceeds smoothly through a sequential imine condensation–isoaromatization pathway, affording a series of synthetically useful aniline derivatives in

• -benzyl-N-substituted anilines. In this work, (E)-2-arylidene-3-cyclohexenones firstly react with primary amines to form cyclohexenylimine intermediates I. Afterward, isoaromatization resulting from imine–enamine tautomerization and exocyclic double bond shift occurs to give rise to stable aniline

• generating a mixture of unidentifiable byproducts. Next, we explored the scope of various primary amines under the optimal conditions (Scheme 4). With 3-cyclohexenones 2a and 2p used, a variety of primary amines 3 successfully participated in the reaction to produce N-substituted anilines 4 in moderate to

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

• the several alcohols and primary amines in the presence of t-BuOK (0.75 equiv) in toluene at 80 °C for 24–48 h and selectively produced the N-alkylated products with good yields (Scheme 3). More interestingly, the first non-noble-metal catalyzed the most challenging N-methylation of amines with

• -methylation of amines with methanol was achieved with lower catalyst and base loading. Sortais et al. reported an elegant example of a manganese-catalyzed N-methylation of primary amines with methanol using catalytic amounts of base. They synthesized a novel Mn(I) complex bearing a bis(diaminopyridine

• bearing bidentate amine-based ligands and studied them in the N-alkylation of aromatic amines with benzylic alcohols (Scheme 17). Under the optimized reaction conditions (140 °C, 24 h), complex Mn8 (2 mol %) was successfully applied for the coupling of various electron-donating and withdrawing primary

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

• and, in terms of gas pressure, took place under mild conditions comparable to the ones reported by Xu et al. (Scheme 31). Chandrasekhar and Sankararaman also tested primary amines under the conditions outlined in Scheme 31, however, the reaction gave the annulated products (as the secondary amines

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• primary amines 1–3 with methyl α-(bromomethyl)acrylate was contemplated first under several typical conditions that all afforded non-synthetically useful mixtures of mono- and diallylation, even if excess of the nitrogen nucleophiles was used. An alternative strategy was thus developed relying on the

• of primary amines and tert-butylsulfinamide (preparation of compounds 5–7 and 8a–c). In a round-bottomed flask under argon, n-BuLi (1.0 equiv, soln. in heptane) was added dropwise to a THF (0.2 mol·L−1) solution of the appropriate primary amine or tert-butylsulfinamide (1.0 equiv) at −55 °C. The

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

• . Notably, carbonylative amidation of a borylated aryl bromide to 26d proceeded well, where a Pd-catalyzed carbonylative amidation reaction would be plagued by undesired Suzuki coupling. Several secondary cyclic and acyclic amines, as well as primary amines were successfully employed as amine coupling