Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• reaction of nitrile, xanthene, terminal alkyne and water to synthesize oxazole was established by Li in 2023 (Scheme 12) [219]. After examining the reaction carefully, the optimized reaction conditions were obtained as follows: a mixture of alkyne 31 (0.3 mmol), xanthene 32 (0.45 mmol), CH3CN (5.0 mL), H2O

• and reductive cascade annulation of o-alkynylbenzamides. An electrochemical intramolecular 1,2-amino oxygenation of alkynes provided indolizines in reasonable yields. The electrochemical multicomponent reaction was also developed for the construction of oxazole. Pyrrole could be prepared by

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

• asymmetric hydrogenation process of α-hydroxy ketones opens up a new pathway for the production of chiral terminal 1,2-diols (Scheme 23) [98]. Kini and Mathews reported the synthesis of novel oxazole derivatives such as 6-(substituted benzylidene)-2-methylthiazolo[2,3-b]oxazol-5(6H)-one by reacting 1

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• -substrates with the potential to react with metal carbenoids in many different ways [14], for example through O–H, N–H or formal C–H insertion, cyclopropanation, or oxazole [20] formation. The 16 co-substrates, selected from available compounds in our laboratory, are shown in Figure 2 (panel A). Many of

• these substrates had more than one potentially reactive site to enable, for example, O–H insertion (C1–5, C8, C11 and C14), N–H insertion (C3, C6, C12, C13 and C15), formal C–H insertion (C1, C3, C4, C12, C15 and C16), oxazole formation (C9 and C10) and cyclopropanation (C7, C10, C14 and C16). To start

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

• , pyridine, and indole, alongside with less common oxygen and sulphur-based heterocycles such as thiophene, thiazole, oxazole. At the end of the section, we will also briefly discuss heteroarylimines which, although not being azo-switches, resemble the geometry of azo-compounds and possess similar

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

• 34f could be used as the starting material to prepare the axially chiral olefin-oxazole 37, which might be a potentially useful ligand in asymmetric catalysis. A possible stereochemical model was proposed as well, involving synergistic activation of both the alkynyl ketone and isocyanoacetate by the

• -derived amino-phosphine L7 as the catalyst, a wide range of oxazole-containing tetra-ortho-substituted axially chiral phenols 47 bearing diverse scaffolds, including naphthyl-phenyl (e.g., 47a), phenyl-naphthyl (e.g., 47b), biphenyl (e.g., 47c), and binaphthyl (e.g., 47d), were obtained in high yields

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• intermediate would meet challenges associated with the instability of enolate derivatives. In their recent study, they successfully developed such a polycyclization taking advantage of a novel spiropyrroline-derived oxazole (SPDO) ligand (L3). As shown in Scheme 7, one-pot condensation of primary amine 40, β

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• azirine dicarboxylic acid 6j, oxazole-4-carboxylic acid 9 was isolated. Apparently, azirine 2j underwent ring opening at higher temperature to nitrile ylide 7, which after cyclization and hydrolysis gave acid 9 (Scheme 3) (cf., e.g. [23]). Next, given that the preparation of 2H-azirine-2-carboxamides from

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• ], requires the presence of a nucleophile at the β-position of the amino acid and occurs exclusively on select amino acids. Specifically, cyclodehydration of a serine or threonine (followed by oxidation or reduction) generates an oxazole, oxazoline, or oxazolidine moiety in the NRP backbone, and the analogous

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• action of radical A leads to intermediate E. The recombination of intermediate E with tert-butylperoxy radical B, following elimination of TsH, and oxidation of oxazole G provides the target peroxide 82 formation. Non-activated С(sp3)–H A number of studies [77][78][79][80][81] are devoted to the

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• reacts with butyllithium, ring closure occurs between the ethynyl and carbamoyl groups, yielding 2,5-disubstituted oxazole-4-carboxylates. This cyclization also occurs when the propargylamine is heated with ammonium acetate, resulting in double activation. Keywords: acid amide; diethyl mesoxalate; N

• -acylamine; oxazole; propargylamine; Introduction Propargylamine is an important motif in the synthesis of heterocyclic compounds [1][2][3][4] and drug discovery [5][6] due to its multifunctionality, which includes a basic and nucleophilic amino group, an electrophilic and dipolarophilic triple bond, and an

• -benzyl-2-(4-methylphenyl)oxazole-4-carboxylate (5a) in 13% yield (Table 3, entry 1). Several conditions were considered, but the yield of 5a did not improve. On the other hand, the addition of two equivalents of water increased the yield, indicating the important role of a stoichiometric amount of water

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• with aniline resulted in low conversion of 1b even at prolonged reaction times (up to 10 days). The addition of molecular sieves, excess aniline, or acid catalysts did not significantly affect the conversion (Scheme 3). 1,3-Diketones with benzothiazole (1c, σm/σp 0.338/0.390) and oxazole (1d, σm/σp

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• mild oxidation of primary and secondary benzylic alcohols to aldehydes and ketones as an alternative to λ5-iodanes. Results and Discussion Initially, we investigated a variety of pyrazole-, triazole-, and oxazole-substituted hydroxy-NHIs previously developed by our group [25]. However, none of them

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• obtain the 1,3-cuneane selectively. The hydroxymethyl group (185a, 185b, 185f), a boronic acid pinacol ester (185c), a phthalimide-protected aminomethyl group (185d) and an oxazole (185e) were, among others, successful as electron-donating groups yielding 1,3-cuneanes. Iwabuchi and co-workers also found

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• . At a concentration of 182 μM, murecholamide exhibits biological activity in inhibiting the migration of HT29 cancer cells. The second HSM is noaoxazole (39), which was discovered in Streptomyces sp. HR41 [79]. This substance has a chemical structure with a methylated oxazole ring at the end of a

• chain-like structure. The structure of noaoxazole is similar to that of inthomycin and oxazolomycin [80][81], but the methylated oxazole ring is a relatively valuable structure found elsewhere only in curromycins A and B (40, 41) and neocurromycin [82][83]. As with curromycin A, the end product of

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• the potential NHC precursor to A, a polysubstituted 3-aminoimidazo[5,1-b]oxazol-6-ium motif B, might be rapidly accessed from an ynamide by sequential oxazole-forming annulation and imidazolium formation steps. The basis of this approach was a gold-catalysed oxazole formation developed in our group

• [20][21] that should facilitate access to different groups at the oxazole C-2 position allowing a range of imidazolium-forming cyclisation strategies to be explored. Glorius and co-workers reported the formation of symmetrical NHCs by imidazolium ring formation from bisoxazoline motifs [22] but

• incorporating the unsaturated oxazole counterparts has not been explored. Results and Discussion Reaction of ynamide 1a with the N-acylpyridinium-N-aminide reagent 2 proceeded in good yield to afford oxazole 3 bearing a C-2 methyleneamino moiety as the first example of a free secondary amine in this annulation

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• (NCS)2(NN) complexes, where NN is a chelating diimine compound such as pyridyl-tetrazole [44], or a pyridine-oxazole [45]. The bond lengths are very similar when comparing the polymorphs 1a and 1b. Nevertheless, the bond angles vary significantly (see Table S2 in Supporting Information File 1

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• effective. This method afforded the products with high selectivity and it could be extended to a variety of substrates, such as benzoxazole, benzothiazole, oxazole, and even acidic hydrocarbons and aniline. Fukuzama and co-workers [91] accomplished the C–H carboxylation of benzoxazole and benzothiazole

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• 2017, the Co-catalyzed CDC for the C5-alkylation of oxazole/thiazole substrates with ethers afforded functionalized ethers in moderate to good yields (Scheme 29a) [91]. In 2016, Du et al. demonstrated that the construction of C(sp2)–C(sp3) bonds also proceeded smoothly with coumarins and cyclic or open

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• , and bearing a spirolactone. As illustrated with the previous examples, access to the final cyclooctane ring was envisioned through a RCM reaction from an appropriate precursor. In a first attempt, compound 57, prepared from oxazole 56, was heated in the presence of G-I catalyst but yielded bicycle 58

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• with amino and nitro groups due to side processes on the electrodes. Cyclic carbamates were oxidized to lactams using ABNO derivatives as electrocatalysts [104] (Scheme 16A). The substrates with easily oxidizable pyrazole and oxazole fragments reacted successfully under these conditions. Under similar

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• benzazoles containing oxazole and imidazole skeletons are the most commonly used scaffolds [1][2][3][4][5]. Therefore, it is crucial for the drug industry to develop methods for their syntheses [1][2][4][6]. For example, conventional benzoxazole synthesis methods involve the condensation of 2-aminophenol

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• the presence of an oxazole or an oxazoline ring. Up to now, it is not clear whether these structural variations are biologically relevant in terms of iron sequestration and cellular uptake. Conclusion In summary, Nocardia altamirensis was found to synthesize various amamistatins under iron-deficient

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• blocks was developed. Regioisomeric methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates were prepared by the reaction of β-enamino ketoesters (including azetidine, pyrrolidine or piperidine enamines) with hydroxylamine hydrochloride. Unambiguous structural assignments were based on chiral HPLC

• analysis, 1H, 13C, and 15N NMR spectroscopy, HRMS, and single-crystal X-ray diffraction data. Keywords: β-enamino ketoesters; heterocyclic amino acids; 15N-labeled 1,2-oxazole; NMR (1H; 13C; 15N); 1,2-oxazole (isoxazole); X-ray structure analysis; Introduction 1,2-Oxazoles (isoxazoles) constitute an

• important class of heterocyclic compounds that plays a fundamental role in drug discovery [1][2][3][4][5][6][7]. Many amino-functionalized 1,2-oxazole derivatives are biologically active substances that include naturally occurring and synthetic neuroactive compounds. Specifically, natural products such as

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• ] developed the synthesis of naphtho[1,2-d]oxazole heterocycles from β-NQS as potential antiviral agents capable of inhibiting the HCV virus. Compound 45 was obtained from β-NQSNa (18) as shown above and reacted with substituted benzaldehyde or furfuryl aldehyde to form naphthoxazoles 51a–i and 53a–c

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116