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

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• limitations that we had encountered in terms of yield and regioselectivity were presumably specific to the ambident nucleophile 6. We considered that a different ambident nucleophile, a phenol, might also give unusual selectivity for production of a bis(aryloxy)fluoromethane over a Reimer–Tiemann formylation

• previously unaddressed question of how heterodihalocarbenes would react with phenols capable of undergoing Reimer–Tiemann formylation. Retrosynthesis of compound 1. Reported bis(aryloxy)fluoromethane syntheses. Reagents and conditions: (a) Cl2FCH, NaOH, 1,4-dioxane/water, 70 °C, 20 min, 90% (+3% (C6F5)3CH

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• +27.9949 Da (formylation) mass shift and an increased RT were observed for most of the IgG and IgA glycopeptides (see Figure S14, Supporting Information File 2 for representative IgG glycopeptide examples). The formylation was conveniently assigned to the glycan part (Figure S15, Supporting Information

• File 2) but may occur at the peptide portion as well [24][25][26]. Formylation is likely introduced by the exposure of the tryptic peptides to formic acid during the acid precipitation of sodium deoxycholate in the final step of the sample preparation and during subsequent storage [24]. Within the

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• using trifluoroacetyl nitrate which was in situ generated from conc. HNO3 and trifluoroacetic anhydride. On the other hand, formylation and acetylation were performed under microwave conditions at 130 °C using triflic anhydride and DMF or dimethylacetamide (DMA) to deliver the corresponding

The biomimetic synthesis of balsaminone A and ellagic acid via oxidative dimerization

• Sharna-kay Daley and
• Nadale Downer-Riley

Beilstein J. Org. Chem. 2020, 16, 2026–2031, doi:10.3762/bjoc.16.169

• previous synthesis of balsaminone A (4) [22] (Scheme 3), silver oxide was used as the oxidative dimerizing agent for the formation of the binaphthoquinone intermediate 13. This was followed by photolytic cyclisation and ortho-formylation to give carbaldehyde 14. Conversion to balsaminone A (4) could then

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• . Condensation with 2-amino-2-methylpropan-1-ol and oxidation with NBS yielded oxazoline 6 in a good yield. Directed ortho-metalation utilizing TMPMgCl·LiCl under mild conditions and subsequent smooth formylation with DMF afforded benzaldehyde 7 (see Scheme 2). Due to rapid decomposition of 7 under ambient and

• -methylbenzaldehyde). Bromofluorenecarbaldehyde 5 The synthetic route to azide-functionalized 7-bromofluorene-2-carbaldehyde 5 started from unfunctionalized fluorene. Double bromination to 14, followed by double methylation of the methylene bridge to 15 and a lithiation/formylation sequence afforded 7-bromofluorene-2

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• of the two functional groups cannot be observed in this case, we could focus on the formation of the dimer-like products. Treatment of unsubstituted derivative 1e (prepared from bromo derivative 21 [26] by formylation via lithiation) in DCM in the presence of a catalytic amount (0.1 equiv) of TFA for

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• ). Derivative 21c was also prepared by the oxidation of 9h with manganese oxide at higher temperature, but the yield was lower (Table 4, entry 5). As part of our interest in further functionalizing octahydropyrrolo[3,4-e]indole-1,3-diones 9, formylation was herein investigated under usual Vilsmeier–Haack

• ]indole-1,3-diones 21a–g by aromatization of 9e–f, 9h–k and 9m.a Preparation of derivatives 22a–e by formylation of octahydropyrrolo[3,4-e]indole-1,3-diones 9.a Calculated [M06-2X/6-31+G(d,p)] relative ZPE-corrected energy (kcal/mol) of the supramolecular complexes (SCs), TSs and adducts (ADs) located on

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• -phenylimidazo[1,2-a]pyridines (Table 2). Before their work, only three reports of such a formylation have been reported in the literature which suffered from certain drawbacks like difficult to prepare starting materials, multistep reaction, high temperature and the use of expensive catalyst [125][126][127