Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• transformation of 145, compound 146 was oxidized with Dess-Martin periodinane (DMP). Subsequent reductive amination with fragment 139 provided an intermediate, which underwent the second reductive amination using formaldehyde. This one-pot process with concomitant deprotection afforded acid 147 in 70% yield over

• excellent site selectivity during the Bz protection. The assembly of the azabicyclic core was achieved in two steps from 291 via reductive amination followed by oxidative removal of the p-methoxybenzyl (PMB) group, giving heptacyclic compound 292. Finally, (+)-18-benzoyldavisinol (293) was synthesized in

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• development of technology-driven sustainable strategies to alfa and beta amination of carbonyls and carboxylic acids derivatives- TECHNO”, financed by EU - Next Generation EU, Mission 4 Component 1 CUP G53D23003280006. M. Gazzotti thanks Università degli Studi di Milano for a PhD fellowship.

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• catalytic kinetic resolution of racemic helical polycyclic phenols through an organocatalyzed enantioselective dearomative amination reaction [30]. The racemic polycyclic phenol derivatives 25, which exist as single diastereomers featuring both central chirality and helical chirality, were readily prepared

• through a [3 + 3]-cycloaddition reaction. By employing the CPA-catalyzed asymmetric electrophilic amination reaction with azodicarboxylate on the phenol moiety, efficient kinetic resolution of 25 proceeded to yield both the amination products 26 and the recovered starting material with high

• enantioselectivity, with an s-factor up to >259 (Scheme 7). Notably, this reaction did not produce the typical arene C–H amination products but instead the dearomative amination products 26, which is believed to be due to the significant steric hindrance surrounding the amination site that impeded the subsequent

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• heterocyclic imines [36][37][38]. The Z-isomers of the unsubstituted derivatives adapt different conformations: T-shaped for the N-phenyl and twisted for the N-pyrazoles. The half-lives follow the same trends already discussed beforehand. In contrast with the azopyrazoles, mono- and di-ortho-amination of the

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• trans-isomer of amide 5. Results and Discussion The protected furfuryl amino alcohols S-2d and R-2d were prepared by reductive amination of furfural (1) with ʟ- and ᴅ-valinol followed by N-protection with Alloc-Cl (Scheme 2). The amino alcohols S-2d and R-2d were then subjected to electrochemical

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

• hypophosphorous acid are commercially available in bulk amounts, however, their usage is understudied in organic processes. While NaH2PO2 has proved to be an efficient four-electron reductant in the catalyst-free reductive amination, the influence of cation in hypophosphite salt has not been studied yet. This

• issue is a fundamentally important factor. In the present work, the reactivity of the hypophosphites of alkali metals (Li, K, Rb, and Cs) in reductive amination was explored for the first time. A set of secondary and tertiary amines was synthesized from various types of carbonyl compounds and amines

• . The remedy for Parkinson’s disease, piribedil, was obtained in high yield. The plausible mechanism of the elaborated process was proposed and supported by DFT calculations. Keywords: amines; DFT; hypophosphites; reductive amination; role of cations; Introduction Sodium hypophosphite, NaH2PO2, is one

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

• of the resulting products in developing chiral organocatalysts was investigated as well. For instance, 28a was converted to a thiourea-tertiary amine 29 through a four-step procedure in an overall 36% yield. This compound was then utilized as the catalyst in the electrophilic amination reaction

• functionality in 63 allowed for versatile derivatizations, such as reduction, reductive amination, condensation, and olefination, which further expanded the structural diversity of the resulting products. Summary and Outlook The past few years have witnessed exciting progress in developing catalytic asymmetric

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• enaminones has attracted much attention over the past decades. Kuwano’s group described the synthesis of enaminones from ethyl ketones via a nickel-catalyzed selective β-amination (Scheme 1A) [31]. The preparation of enaminones can also be achieved by the reaction of aldehydes and calcium carbide in the

• presence of amines and CuI as catalyst, as reported by Zhang and co-workers (Scheme 1B) [32]. On the other hand, Li et al. disclosed a silver-catalyzed amination of propargyl alcohols to afford enaminones (Scheme 1C) [33]. Although these new methods provide a wide variety of enaminones, there are

• the reactivity of unsaturated esters towards an aza-Michael addition is the use of transition metal complexes as catalysts/promoters [40][41][42]. Considering this background, we reasoned that Ni(II) could be a suitable catalyst for the amination of unsaturated systems. Initial investigations were

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• -workers demonstrates that the efficient and green direct C–H amination of benzoxazoles can be catalyzed by copper chloride salts in acetonitrile in the absence of any acidic, basic, or oxidizing additives [8]. Both CuCl and CuCl2 were found to be extremely efficient in promoting the reactions, which

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• S.P.A., Via Pavia 1, Gropello Cairoli, Italy Department of Chemistry, NIS Interdepartmental Centre and INSTM Reference Centre, University of Turin, Via Pietro Giuria 7, 10125 Turin, Italy Cube Labs Spa V. Giulia Caccini 1, 00198 Roma, Italy 10.3762/bjoc.21.108 Abstract The C2-amination of benzoxazole

• offers wide-ranging potential for substrate expansion and the functionalisation of bioactive compounds. This study presents a green and efficient C–H amination, catalysed by CuCl and CuCl2, in acetonitrile without acidic, basic or oxidant additives that is accelerated by microwave (MW) irradiation and is

• -amination of benzoxazoles by transition-metal-catalysed reactions that traditionally involve aryl halide scaffolds [11][12][13][14]. However, these procedures entail disadvantages that need to be overcome if green chemistry criteria are to be met; high temperatures, long reaction times, the need for ligands

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• the concurrent generation of the carbon cation 55. This cation was subsequently trapped by a nucleophile, leading to the formation of product 54. This system demonstrated a broad applicability for the general nucleophilic amination of benzylic C–H bonds. The substrate's scope and selectivity were

• radical under visible light. Nucleophilic amination of C(sp3)–H enabled by amidyl radical under visible light. Direct heteroarylation of C(sp3)–H and C(sp3)–H without the presence of strong bases, acids, or oxidants. Xanthylation of C(sp3)–H addressed by amidyl radical under visible light. Xanthylation of

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

• -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

• -chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine were synthesised, purified (≥95% purity, determined by 1H and 13C NMR and HPLC–MS analysis) and assayed for in vitro antimalarial activity. Results and Discussion Synthesis of aminated triazolopyrazine analogues The amination of 5-chloro-3-(4-chlorophenyl)-[1,2,4

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

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• asymmetric allylic amination of allylic esters with isatin derivatives 11 as nucleophiles. The reaction proceeds efficiently, yielding the products (S)-13 with good-to-high enantioselectivity. A scale-up reaction was also successfully conducted at a 1 mmol scale. Additionally, when malononitrile was added to

• the resulting product (S)-13a in the presence of FeCl3 as the catalyst, the corresponding malononitrile derivative (S)-16 was obtained without any loss in optical purity. Keywords: asymmetric allylic amination; axial chirality; isatin; palladium catalysis; P,olefin-type chiral ligand; Introduction

• activity against Huh7.5-FGR-JC1-Rluc2A cells, which carry HCV gt 2a [13]. Therefore, developing asymmetric reactions that simultaneously form a carbon–nitrogen bond and construct a chiral center is of great importance. Although a relatively large number of asymmetric allylic amination reactions using

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• -monomethylation of the primary amino group of compound 25 by alkylation with methyl iodide or by Eschweiler–Clarke reductive amination with formaldehyde and formic acid were unsuccessful, because the dimethylated byproduct was also formed, even when one equivalent alkylating agent was used. Finally, our efforts

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• represents a highly challenging direct C(sp3)–H asymmetric amination. Mechanistic insights: When using a bulky, electron-rich chiral bisphosphine ligand L6, the glycine ester substrate coordinates with the copper catalyst to form a key intermediate complex Int-26. The sterically hindered and electron-rich

• achieved selective synthesis of either enantiomer of a target product by controlling the reaction duration (Scheme 13) [42]. When performing the asymmetric intermolecular allylic amination of 6-hydroxyisoquinoline (49) with tert-butyl(1-phenylallyl)carbonate ((rac)-50) using an Ir catalyst derived from [Ir

• in the absence of a Brønsted acid additive, the opposite enantiomer 52 was obtained. Mechanistically, an initial kinetic resolution (KR) of (rac)-50 occurs via an Ir-catalyzed asymmetric allylic amination. Due to the higher reactivity of (S)-50, it reacts with 6-hydroxyisoquinoline within 6 minutes

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• ; hydrazones; isocyanides; Introduction Catalytic applications of non-toxic earth abundant metals like calcium are currently on the rise [1][2][3][4]. Prominent recent examples that witness the versatility of calcium catalysis include calcium-catalyzed amination of π-activated alcohols [5], the Beckmann

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• chiral nitrogen nucleophile as shown below. To the best of our knowledge, the electrosynthesis of gem-α,α-diamino acid derivatives 6 has not been accomplished, and all published electrochemical amination examples under Hofer–Moest conditions [5] targeted either N-substituted heteroarenes [6] or aminals

• was not extracted from background-corrected voltammograms. All CV graphs are plotted using IUPAC polarographic convention. Selected examples of α,α-disubstituted cyclic amino acids in drug design. Electrochemical decarboxylative amination reactions. A) Cyclic voltammograms of 6a and 9a at 3 mM and 6

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• 8 was obtained in good yield of 61% through reductive amination with excess formaldehyde and NaBH3CN as reductant, the selective installation of only one methyl group, providing monomethyl aniline 7, proved to be more troublesome. Either reductive amination using the same protocol, but under strict

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

• -acetyl diazocines 2 and 3 via Buchwald–Hartwig amination. Equivalents are normalized to the used amount of N-acetyl diazocine starting material. Photophysical properties of N-acetyl diazocines 1-4, 7–14, 17, 19–21, and 23 in acetonitrile. Photophysical properties of N-acetyl diazocines 1, 13, and 21 in

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• reductive amination to form the hydroxyalkyl handles, which were further converted to the haloalkyl or mesyloxyalkyl-modified target compounds. In addition, we report hydrogenation conditions for preQ0 and DPQ0 that allow for cleaner and faster access to preQ1 compared to existing routes and provide the

• of the electrophile. We thus identified aldehydes 9 and 10 as suitable branching points, which were easily derivatized to their aminomethyl-modified preQ1 analogs by reductive amination (Scheme 3). Their syntheses by Raney-Ni reduction of nitriles 7 and 8, previously described by Gangjee and co

• -workers [33], proceeded cleanly in our hands. In the case of compound 4a, the chloropropyl moiety was directly installed by reductive amination of 9 with 3-chloropropylamine hydrochloride under basic conditions. A two-step reaction sequence, however, was necessary to generate derivatives 4b–e and 3a

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• reductive amination to stabilize imine cages, and the resulting amine cages gain solubility from increased flexibility at the cost of losing some structural rigidity [42][43][44]. Metastable conformations – programming cavity shape and symmetry: Unlike non-covalent/dative assemblies, covalently linked cages

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• synthesis of iVeliparib-AP6 [5] starts with a nucleophilic aromatic substitution (SNAr) reaction wherein 4-fluorothalidomide (1) reacts with amino-PEG7-OH 2 to give alcohol 3 (Scheme 1). Subsequent alcohol oxidation followed by reductive amination of the resulting aldehyde 4 with veliparib [6][7] provides

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

• . Subsequent intramolecular amine transfer to the radical cation intermediate 53, followed by ligand exchange, yields amination product 49 and Cu(I) species 55. Cu(II) catalyst 50 is regenerated by anodic oxidation, thereby completing the catalytic cycle. In 2019, Nicholls et al. reported a Cu-catalyzed

• directed C–H amination of benzamides with secondary amine electrophiles independently (Figure 11) [61]. In 2023, De Sarkar and Baidya reported the Cu-catalyzed electrocatalytic azidation of N-arylenamines, followed by denitrogenative annulation for quinoxaline synthesis (Figure 12) [62]. Only 0.5 mol

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

• Michael-type addition of 5-aminoindazole to afford the first coupling product XXXVIII. The subsequent intramolecular amination and dehydration then leads to the final product (Scheme 31) [50]. Polycyclic spiroindoline-3,4’-pyrano[3,2-b]pyran-4-ones 43 were synthesized exploiting the three-component