Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• elucidate the bioactive conformations, of other simple linear amines too. A gauche alignment of the vicinal C–N and C–F bonds is consistently seen [156], whether the scaffold is a primary amine (e.g., tetrafluorovaline, 91 [157]), a secondary amine (e.g., N-methyl-ᴅ-aspartate(92) [158][159]), or a tertiary

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

• isocyanide component is preferred over the formation of the imine, probably because of the high reactivity of the carbonyl compound or the low stability of the imine. After cycloaddition, the tosyloxazoline derivative undergoes an addition at C-2 by the primary amine, followed by elimination of the

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

• Pd-catalyzed cross-coupling reactions, allowing the formation of C–C and C–N bonds in the o-position of the aryl chalcogen compounds. α-Aminophosphonates 14 were the result of a one-pot condensation of an aldehyde, a primary amine and phosphite P(OMe)3 with copper triflate acting as Lewis acid

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• glutamate) (PBLG) as the hydrophobic block, which was done to prevent ending on a primary amine in the final product which could disrupt self-assembly due to its ionizable nature. Subsequently, PBLG served as a macroinitiator for the polymerization of sarcosine NCA, yielding the final polymer with high

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• ]. One of the most studied and inexpensive routes to synthesize substituted phenethylamines focuses on the reduction of their α,β-unsaturated nitroalkene analogue (β-nitrostyrene), where both the double bond and the nitro group need to be reduced to deliver the corresponding primary amine. Their

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• groups (V), which proved to be useful in the transfer of imine radicals [17]. Bolm et al. contributed also to this topic by introducing a sulfoximidoyl-containing benziodoxolone (VI) [18]. Recently, our group disclosed the first HIRs bearing a primary amine moiety, the benzylamine benziodoxolone reagent

• primary amine-containing HIRs, or it might be due to the inability of the benzyl moiety to stabilize the sulfenate ion during the reaction. For tert-butyl 3-(p-tolylsulfinyl)propanoate (4a), and similarly to the outcome obtained for BBX 2a, sulfonamides 5ab and 5ac were obtained with moderate yields. The

• a drastic decrease in the yield of sulfonamide 5aa was observed, suggesting that the benzylamine-transfer reaction might occur via a radical mechanism. This finding supports the hypothesis that, beyond the ionic mechanism previously explored for our electrophilic primary amine transfer reagent [4

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• commercially available primary amine, 1-(3-aminopropyl)pyrrolidin-2-one completed the total synthesis of the natural product in an overall yield of 1.5%. The NMR data comparison of the natural product and our synthetic compound was essentially identical. Due to our interest in the identification of potential

• –activity relationship data, leading to speculation over the moieties responsible for their antibiotic effects. A reduction in the number of amines in the polymeric chain and the absence of a primary amine was noted to decrease bioactivity by Xu et al. [7]. Research reported by Khan et al. in 2014 [9] also

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• trifluoroethanol as the solvent and at room temperature [23][24][25][26]. In the initial reaction, propargylamine served as a bifunctional reagent, with the primary amine group participating in the first step and the terminal alkyne promoting the subsequent heteroannulation. (Scheme 2). As observed in our previous

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• . In addition, whereas tert-butylzinc iodide was efficient in the multicomponent coupling (99% yield), tert-butylzinc bromide led to a very low yield (16% 5kaa). The coupling presented some other limitations. It was not possible to carry out the reaction when a primary amine was employed. In addition

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

• . The fragmentation of the triazole ring leaving the primary amine and b-ion resulting from the fragmentation of the TEV-recognition peptide sequence. The chemical cleavage of the linker to release probe–peptide conjugates is achieved mainly by the change of the pH or via reducing conditions to release

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

• [15][16] or iminium-ion catalysis [17] under ball-mill conditions are scarce, in contrast to the abundance of transformations catalyzed by such covalent catalysis. Among the numerous organocatalytic reactions facilitated by primary amine-based iminium ions, Michael-type additions deserve special

• by extended reaction times, sometimes up to 168 hours. An intriguing example involves the use of a bifunctional primary amine-sulfonamide catalyst, which activates benzylideneacetone towards dibenzyl malonate, with the presence of water accelerating the reaction [25]. An alternative approach, where

• product with 93% ee after 24 h, while the bifunctional primary amine-thiourea catalysts (system B) required 4 days to provide an adduct with similar enantioselectivity. Prolonged reaction time is in general the innate nature of organocatalytic reactions employing iminium activation approaches. With the

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

• triethylsilane in TFA-CH3Cl, resulting in the N-methylated amino acid as the final product [38]. The third method for chemical N-methylation involves the use of protection groups that also enhance the reactivity of the primary amine (Figure 2). Once the amine is deprotonated, an electrophilic methylation reagent

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• NRPS-derived macrolactam ureidopeptide, bulbiferamide (27, Figure 10), was isolated and characterized from a coral-derived Microbulbifer sp. C10-1 by Igarashi and co-workers [7]. The ureido linkage did not allow for the peptide main chain in 27 to possess a terminal primary amine and none of the side

• chains possessed a nucleophilic primary amine. Curiously, the macrocyclizing amide bond was found to exist between a Trp side chain indole nitrogen and the C-terminal carboxylate. To the best of our knowledge, this was the first example of the involvement of a Trp indole in macrolactam formation in

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• 10.3762/bjoc.20.136 Abstract The enantioselective 1,4-addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones catalyzed by a cinchona alkaloid-derived primary amine–Brønsted acid composite is reported. Both enantiomers of the anticipated pyrazole derivatives were obtained in good to excellent

• metal catalytic conditions. In continuation of our work in the field of organocatalysis [26][27][28][29], herein, we present the Michael addition reaction of 4-unsubstituted pyrazolin-5-ones with arylidene/heteroarylideneacetones using cinchona alkaloid-derived primary amine catalysts. The developed

• primary amine catalysts (see Table S1 in Supporting Information File 1) in toluene at room temperature (30–32 °C). When the test reaction was conducted in the presence of 15 mol % of 9-amino-9-deoxy-epicinchonidine (I) as catalyst [30] for 12 h and treated with Ac2O followed by DABCO, the reaction gave

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

• ; primary amine; Introduction Aniline derivatives possessing arylmethyl substituents at the ortho position are an important class of amines. They have a wide variety of practical applications, ranging from anti-depression [1], being δ receptor stimulants in analgesic pharmaceuticals [2], to antioxidant

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• suitable for the coupling to peptides on resin, prepared by solid-phase peptide synthesis (SPPS) [35]. The detailed conditions for the amide-forming reaction were optimized using biscarboxylic acid-substituted C60 derivative 3 and a similar peptide with a primary amine derived from γ-aminobutyric acid

• on resin, a GABA residue was attached to the N-terminus of the peptide in order to provide a less-hindered primary amine, enabling an efficient amide conjugation reaction with biscarboxylic acid-substituted C60 derivative 3. Compound 3 was prepared by Prato reaction of C60 and an N-glycine derivative

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• also compatible with these mild conditions (4y–aa, 51–72%). Additionally, the diazo derivative of epiandrosterone was reactive in this protocol, giving the product 4ab in 59% yield. Delightedly, this procedure was successfully applied to aromatic amine (N-methylaniline), primary amine (aniline) and

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• 52% (3p) yields, respectively. If the chains did not involve a carbonyl group, the yields were much lower (3q, 25%; 3s, 29%, and 3t, 29%). When a pyrrole ring was used instead of indole, the reaction proceeded but gave the product in low yield (3r). We did not explore the reaction with a primary

• amine functionalized substrate, because of competition of the reaction site during the synthesis of substrates. However, an amide-substituted indole furnished a clean product without competition; for example, product 3u was derived from melatonin with an amide functional group, whose reaction to the

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

• 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

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• stereocenter bearing primary amine and trifluoromethyl functionalities associated with appreciable enantiocontrol. The substrate scope was investigated by the variation of sterically and electronically divergent aryl substituents in the ketimines but the enantioselectivity was markedly lowered with sterically

• after recrystallization. Subsequent ozonolysis of the terminal alkene functionality with a follow-up reduction furnished primary alcohol 134 which was transformed into the azide 135. Reduction of the azide 135 was accompanied by debenzylation, was followed by tosylation of the primary amine and exchange

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• proposed by Wang [55] (Scheme 2b), 2,5-dimethoxytetrahydrofuran (2) is first protonated with acetic acid, followed by ring opening to form carbocation B. In the following step, primary amine 1 nucleophilically attacks carbocation B to produce intermediate C, which, after proton rearrangement and the

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

• , 95%) groups were tolerated under the reaction conditions. The presence of a primary amine in the substrate was tolerated under the reaction conditions (1o), undergoing efficient hydroboration to give the dihydrochloride salt (87%), although an increase in HBpin equivalents (5.5 equiv) was required

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

• synthetic method showed very limited substrate scope. Only less bulky primary amines underwent the first aza-Michael addition and then intramolecular nucleophilic substitution. However, aromatic amines, aniline, 2,3-dihydro-1H-inden-4-amine, and the bulky aliphatic primary amine adamantylamine did not

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• ]. Beyond their resemblance to peptides, the obvious interest in this family of peptidomimetics arises from their ease of synthesis by the modular submonomer protocol [9] which enables the incorporation of numerous primary amine synthons in a sequence-controlled manner [10], and application of solid