Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• . Formylation of enantioenriched hexanone 93 (90% ee) with NaH/HCO2Et, followed by methylation produced two separable isomers, 94a and 94b, in yields of 24% and 31%, respectively. Treatment of these isomers with H2O2 smoothly delivered the carboxylic acids 96a and 96b stereospecifically with excellent

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• by the Yang group [22]. Installation of the hydroxymethyl group in 4 was achieved through sequential formylation and reduction. Compound 4 then underwent a one-pot, substrate-controlled diastereoselective Johnson−Claisen rearrangement/acetylation to install ester 5. Treating 5 with m-CPBA (meta

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

• a C1 building block for the N-formylation of secondary amines to formamides under catalyst-free conditions and air as oxidant. This method was applied to different aromatic and aliphatic (both cyclic and acyclic) amines (Scheme 3) [31]. Already in 1955, Parham and Reiff reported the synthesis and

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• introduce the carboxylic acid group a sequence of formylation/oxidation reactions was used. Vilsmeier–Haack reaction of 1 afforded 6-oxoindolo[1,2-c]quinazoline-12-carbaldehyde (2) (Scheme 1). All attempts to oxidize the aldehyde group of 2 to the corresponding carboxylic acid were hampered by the oxidative

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• ). Benzothienopyrrole 3b was methylated using the MeI/NaH system into 1-methyl-substituted derivative 6 in 81% yield. With the same efficiency, when compound 3b was treated with di-tert-butyl dicarbonate in the presence of 4-(dimethylamino)pyridine (DMAP), Boc-derivative 7 was obtained. Finally, the formylation of 3b

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• blocks, we herein report electrophilic formylation of naphthalene-fused [3.3.3]- and [4.3.3]propellanes as the first selective single-point functionalization by virtue of through-space electronic communications between the naphthalene units. The propellane skeletons have well-defined 3D structures and

• followed by acid-mediated condensation. The linear copolymers show good solubility and carbon dioxide adsorption. Keywords: alternating copolymer; building block; formylation; gas adsorption; propellane; Introduction Combination of sp2- and sp3-hybridized atoms in core π-skeletons [1][2][3] is a key to

• a single functional group to a whole skeleton of [4.3.3] and [3.3.3], using formylation [55][56]. The reaction is electrophilic, and the substrates are effectively deactivated toward further reactions upon introduction of an electron-withdrawing formyl group because of through-space electronic

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• yield of 88%. (R)-Methyl 6-oxopipecolate (7) was converted under Vilsmeier–Haack conditions [35][40][41] to undergo N-formylation and concomitant enol bromination to give product 2 (Scheme 2). Due to slow degradation of the bromide 2, the subsequent cross-coupling reaction was conducted immediately

• for (2R,6S)-13 and b) for the chair conformations of (2R,6R)-13. ᴅ-2-Aminoadipic acid (1) can be used to generate C6 aryl and alkynyl-modified pipecolic acid derivatives. Methyl ester formation, followed by cyclization, N-formylation, as well as bromination under Vilsmeier–Haack conditions. Suzuki

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

• were crowned by success. In order to completely avoid the possibility of overmethylation [37], the methyl group was introduced by N-formylation of the primary amine group of 25 to give congener 26, followed by reduction of the formyl group with borane–dimethyl sulfide complex [38] to result in

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

• the desired thienopyrimidones 5a–e, quinolinopyrimidones 6a–e and indolopyrimidones 7a–e, respectively, as reported in the literature [42][44]. In accordance with the reported mechanism, after the initial formylation of the amino group at position 2, an intramolecular nucleophilic attack by the NH

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• -glycosyl aniline β-22b which was formylated to give 22c in 74% yield (Scheme 16) [24]. Product 22c resides as a mixture of α- and β-anomers, because an anomeric equilibrium was activated during the acid-mediated formylation. The cyclization of 22c with oxalyl chloride, carried out under forcing conditions

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• successfully synthesized on a gram scale through a three-step reaction sequence. The process began with 2,6-diisopropylphenylamine, which underwent alkylation, formylation, and substitution reactions. The carbene synthesis was then achieved via a two-step process involving ynamide annulation, followed by

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

• from the dichloromethane extracts of the leaves of Caesalpinia platyloba by column chromatography, they performed a Vilsmeier–Haack formylation at the furan ring (Scheme 14) obtaining aldehyde 35 in 92% yield. This, in turn, was used as starting material in a GBB-3CR performed at room temperature to

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• bisorbicillinoid family. Substrate 33 for SorbC-catalyzed enzymatic transformation was synthesized in 3 steps from phenol 35 via formylation and subsequent reduction to introduce a methyl group, followed by a Friedel–Crafts acylation with 36 (Scheme 4B) [39][40]. The in vitro enzymatic transformation of 33 by

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

• good yield. The new nitrenoid reagent 7 is readily prepared from 2,6-diisopropylphenylamine in three steps. Alkylation with methyl bromoacetate is followed by formylation of 11 and then substitution [21] of 12 with N-aminopyridinium iodide to yield the bench-stable and crystalline N-acylpyridinium

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• complete decomposition. With the desired naphthylamines in hand, we were able to complete our synthesis of four chelerythrine variants as shown in Scheme 7. After N-formylation providing intermediates 11 and 12 in good yield, a three-step sequence was performed: Suzuki coupling of the aryl bromide with one

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• prepared by Wittig methylenation of commercially available bis(2-formylphenyl) ether (119), whereas a formylation–Wittig methylenation sequence of commercial diphenylsulfone (120) and protected bis(2-bromophenyl)amine 121 afforded the S- and N-tethered diene, respectively. Ruthenium (2nd generation Hoveyda

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• of zirconium enolates, presumably, due to the considerable steric hindrance caused by bulky ligands around the Zr center. Fletcher investigated the formylation of zirconium enolates with the Vilsmeier–Haack reagent [70]. Interestingly, the reaction afforded chloroformylation rather than simple

• formylation products. The methodology was later exploited in the expedient synthesis of the Taxol core (Scheme 34) [71]. Tandem conjugate borylations and silylations Chiral organoboron compounds are well-known synthetic building blocks with diverse possibilities for subsequent derivatization (e.g., oxidation

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• reported for vinyl sulfides, including dihydrodithiin 13 (Scheme 5a) [36]. In fact, Parham has found that fully unsaturated dithiins can undergo this electrophilic formylation, but at the same time also undergo a ring contraction and an aromatizing desulfurization to yield thiophenes as the main formylated

From amines to (form)amides: a simple and successful mechanochemical approach

• Federico Casti,
• Rita Mocci and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 1210–1216, doi:10.3762/bjoc.18.126

• mechanochemical conditions are presented. The two methodologies exhibit complementary features as they enable the derivatization of aliphatic and aromatic amines. Keywords: acetamides; formamides; mechanochemistry; N-formylation; p-tosylimidazole; Introduction The preparation of N-formylated and N-acetylated

• ][50][51][52][53][54], no systematic report of N-formylation and N-acetylation by ball milling has been reported yet. Here, we describe two complementary procedures to prepare formamides and acetamides, applied to primary and secondary aromatic and aliphatic amines. The methodologies directly involve

• efficiently took place even in the presence of a catalytic amount of p-Ts-Im without significant differences in the reactivity. This data led us to question the effective role of p-Ts-Im in promoting the formylation reaction, which could exploit its role as the sole solid auxiliary of grinding. p

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• (trimethylsilanyl)diseleno[2,3-b:3′,2′-d]thiophene ((TMS)2-bb-DST), and 2,5-di(trimethylsilanyl)diseleno[2,3-b:3′,2′-d] selenophene ((TMS)2-bb-DSS) were used as starting materials to synthesize three S-shaped double helicenes (i.e., DH-1, DH-2, and DH-3) through monobromination, formylation, the Wittig reaction

• -carbaldehyde (4b) [27], and 5-(trimethylsilyl)diseleno[2,3-b:3′,2′-d]selenophene-2-carbaldehyde (4c) [27] were prepared via monobromination and formylation reactions with (TMS)2-bb-DTT, (TMS)2-bb-DST, and (TMS)2-bb-DSS as starting materials according to the literature. In (TMS)2-bb-DTT, (TMS)2-bb-DST, and (TMS

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 end product of the pathway in N. altamirensis DSM 44997. Previous studies have demonstrated that, in nature, hydroxamates arise from the oxidation of terminal amino groups in amino acid side chains, followed by formylation or acylation of the resulting hydroxylamines. While the oxidations are

• catalyzed by flavin-dependent monooxygenases [12][13][14][15][16], the carbon transfer is mediated either by tetrahydrofolate-dependent formyl [17] or by acyl-CoA-dependent acyl transferases [13][15][16]. It is widely assumed that the oxidation precedes the formylation or acylation [17][18][19][20][21][22

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• nickel catalysis enables these protocols at room temperature with ample substrate scope (Scheme 8). Unsymmetrical amine substrates favored arylation at the methylene C‒H over methyl C‒H with good regioselectivity [59]. In 2017, Doyle utilized the photoredox nickel catalysis approach for the formylation

• . Arylation of α-amino C(sp3)‒H bonds by in situ generated aryl tosylates from phenols. Formylation of aryl chlorides through redox-neutral 2-functionalization of 1,3-dioxolane (13). Photochemical C(sp3)–H arylation via a dual polyoxometalate HAT and nickel catalytic manifold. Photochemical nickel-catalyzed α

Substituted nitrogen-bridged diazocines

• Pascal Lentes,
• Jeremy Rudtke,
• Thomas Griebenow and
• Rainer Herges

Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

• anhydride of acetic acid and T3P (propanephosphonic acid anhydride). The formylation of NH-diazocines 9a–c was accomplished with chloral [23] under non-acidic conditions. Investigation of the photophysical properties The UV–vis spectra of diazocines 10a–c, and 11a–c were recorded in acetonitrile at 25 °C

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• scaffold [4]. The Guareschi–Lustgarten reaction is at the basis of the pharmacopoeia assay of thymol (3) [5], and investigation on the color associated with the reaction eventually led to the discovery of the Reimer–Tiemann formylation of phenols [6]. Conversely, the third Guareschi eponymic reaction, the

• chloroform–phenol reaction attracted the attention of Karl Reimer (1845–1883) and Ferdinand Tiemann (1848–1899), who set out to investigate the chemistry involved in the color formation, eventually discovering the phenol formylation that bears their name [6]. The Guareschi reaction, then extensively applied

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• appeared at δH 7.98 (d, J = 9.1 Hz, 1H) and δH 7.35 (d, J = 9.0 Hz, 1H) indicating an ortho-relationship between the hydrogen atoms positioned on the phenolic ring. Several methods of formylation of 13 were attempted, e.g., Vilsmeier formylation, where only the unstable formate ester was formed. Following

• the Duff formylation procedure, only traces of aldehyde 16 were detected. Rieche formylation with either SnCl4 or TiCl4 resulted in a low conversion of the starting material and only traces of 16 due to the limited solubility of 13 in DCM, DCE, or chloroform. Furthermore, 16 was isolated after a

• Reimer–Tiemann formylation; however, only in 13% yield. Finally, Casnati–Skattebøl formylation of 13 using MgCl2, iPr2EtN, and paraformaldehyde, i.e., (CH2O)n, has been successful in regioselectively affording aldehyde 16 in a reasonable yield of 39%. The regioselectivity of compound 16 was confirmed by