Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• -cyanophenylacetonitrile afforded HBC 4 and HBC-like ligands 5 and 6 as bright orange solids. Finally, the bromo group was introduced under Appel conditions with carbon tetrabromide and triphenylphosphine to give the fluorophores 7, 8, and 9, with linker lengths of two, three, and five atoms. Unfortunately, this strategy

• to avoid precipitation of the compounds 7, 8, 9, and 11 during long (>12 h) incubation times). In view of these results, we further focused on HBC derivatives with the high-yielding C3 handle and sought a variation of the electrophile. Thus, adapted Appel reaction conditions using N-chlorosuccinimide

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

• subjected to Appel conditions in DMF, using elemental iodine as the halogen source. Notably, we were not able to efficiently generate the corresponding bromides with the same strategy. The preQ1 derivative 3a was synthesized in a 2-step reaction sequence analogous to the DPQ1 derivative 4b, while four steps

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• ). Acknowledgements I am grateful to my co-workers who contributed to the work included in this account article. These are (in alphabetical order): Drs Uwe Albrecht, Bettina Appel, Alina Bunescu, Friedrich Erben, Edith Holtz, Muhammad Farooq Ibad, Ilia Freifeld, Viktor O. Iaroshenko, Abid Obaid-ur-Rahman, Muhammad A

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• ]octane ring-system via the chlorosulfite intermediate. Analogous allylic alcohols with endocyclic and exocyclic unsaturations underwent chlorination without rearrangement due to formation of allylic cations. The rearrangement was also demonstrated using Appel conditions, which gave similar results via

• reaction with SOCl2, and the previous work with DAST, suggested that good leaving groups were required to drive the migration reaction. A variety of processes are known for deoxyhalogenation, and it was thought that alternatives to SOCl2 could also be used to promote the oxygen migration. When Appel

• oxyphosphonium group was observed at δ 4.44 ppm, shifted downfield relative to the starting alcohol 10a along with resonances for the phenyl groups. The isolation of the products using the Appel conditions was more challenging than for the reactions with SOCl2 due to the difficulties separating the products from

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

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• of Science, Port Said University, 42522-Port Said, Egypt 10.3762/bjoc.19.9 Abstract Cholesterol reacts under Appel conditions (CBr4/PPh3) to give 3,5-cholestadiene (elimination) and 3β-bromocholest-5-ene (substitution with retention of configuration). Thus, the bromination of cholesterol deviates

• from the stereochemistry of the standard Appel mechanism due to participation of the Δ5 π-electrons. In contrast, the subsequent azidolysis (NaN3/DMF) of 3β-bromocholest-5-ene proceeds predominantly by Walden inversion (SN2) affording 3α-azidocholest-5-ene. The structures of all relevant products were

• –517. Keywords: Appel reaction; azidolysis; cholesterol; crystal structure; Walden inversion; Introduction 3β-Hydroxycholest-5-ene (cholesterol) is a structural and physiologic amphipathic steroid in human and animals as well. Cholesterol is an essential component of the plasma membrane, where it

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• TBS deprotection giving the bicyclo[3.2.1]octane subunit with a good yield of 74%. A sequence involving diastereoselective reduction of ketone 24 with SmI2, Appel reaction to convert the primary alcohol to the corresponding primary alkyl iodide followed by a MOM protection of the secondary alcohol

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• , syntheses of C6-modified mannose 1-phosphates 13 and 17 were developed (Scheme 1). The synthesis of 6-amino-6-deoxymannose 1-phosphate 13 started from protected thioglycoside 10 [6]. A two-step modification using Appel halogenation followed by nucleophilic substitution with azide furnished 11. Conversion of

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• -triethylsilyloxy-1,3-hexadien-5-yne (87) in the presence of 42 gave the dihydropyran 88 with excellent enantioselectivity. A Rubottom oxidation, protection of the C-4 alcohol, and a Wittig methenylation afforded 89. The selective deprotection of the primary TBS ether, followed by an Appel iodination and the

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• (III)–P(V) redox cycle, such as in catalytic Wittig-, aza-Wittig-, Staudinger-, Appel- and other reactions [16][17][18][19][20][21]. The ring strain of the four- and five-membered derivatives makes them highly susceptible to deoxygenation, thus they are ideal organocatalysts in P(III)–P(V) redox

Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• % overall yield. Installation of the cationic head was performed in two steps: first bromination of 11 via Appel reaction, followed by treatment with trimethylamine to give 2 in 35% overall yield. Photoswitch 2 is the first example of a bifunctional, asymmetrically substituted 4FAB chromophore that actually

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• ditosylation reactions and for the observed partial regioselectivity in reaction 2 (Scheme 2). Additionally, a Vilsmeier–Haack/Appel-type iodination reaction was performed with β-CD, using triphenylphosphine (PPh3) and iodine (I2) in DMF (reaction 3, Scheme 2). This reaction is known to be selective for the

• ,6D-diazido derivatives (reference 2 and reference 3, respectively, in Scheme 1). According to this observation, under the used reaction conditions in the Vilsmeier–Haack/Appel-type iodination the 6A,6B-substitution does not take place and only the 6A,6D- and 6A,6C-substituted products are formed in

• - and 6A,6D-, with the 6A,6C-regioismer being favored. • The preparation of the primary-side diazido-β-CDs through a one pot Vilsmeier–Haack/Appel-type iodination reaction also generates only two regioisomers, 6A,6C- and 6A,6D-, in higher yields than above and with the 6A,6D-regioisomer being slightly

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

• Clémentine Minozzi,
• Jean-Christophe Grenier-Petel,
• Shawn Parisien-Collette and
• Shawn K. Collins

Beilstein J. Org. Chem. 2018, 14, 2730–2736, doi:10.3762/bjoc.14.251

• photocatalyst, Cu(tmp)(BINAP)BF4, was found to be active in a photoredox Appel-type conversion of alcohols to bromides. The catalyst was identified from a screening of 50 complexes and promoted the transformation of primary and secondary alcohols to their corresponding bromides and carboxylic acids to their

• anhydrides. The protocol was also amendable and optimized under continuous flow conditions. Keywords: Appel; continuous flow; copper; halides; photocatalysis; Introduction Synthetic photochemistry and photocatalysis continues to influence molecular synthesis [1][2][3][4]. In exploring photochemical

• reactivity manifolds, there exists the potential to discover new methods to construct important molecular fragments, as well as revamp traditional chemical transformations. One such process is the Appel reaction [5], which employs PPh3 and an electrophilic halogen source to promote the formation of an

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• the two phosphorus atoms was pre-formed. Thus, we set out to prepare a tetraalkenyl metathesis precursor as shown in Scheme 3. The first step, a previously reported reduction of commercial 1,14-tetradecanedioic acid to 1,14-tetradecanediol (7) [37], was followed by an Appel reaction to give 1,14

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• et al. using a modified Appel-type procedure [121]. A striking oxidation reaction of alcohols to carbonyl compounds was disclosed by Mitsunobu and colleagues, involving the sterically hindered nitrophenol 130 [122]. With sugars like 129, the Mitsunobu glycosylation is hampered, and instead an

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• Ruth Suchsland Bettina Appel Sabine Muller Institut für Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Felix-Hausdorff-Str. 4, D-17489 Greifswald, Germany 10.3762/bjoc.14.28 Abstract The preparation of protein libraries is a key issue in protein engineering and biotechnology. Such

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• synthetic route to tCO derivatives started from the same 3´,5´-di-O-acetyl-5-bromo-2´-deoxyuridine (21, Scheme 5) as Lin et al. used, but was instead activated for a condensation using Appel chemistry [41][49]. Compound 21 was activated using PPh3 in CCl4 which converts the O4 to a 4-Cl and used in situ

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Total synthesis of leopolic acid A, a natural 2,3-pyrrolidinedione with antimicrobial activity

• Atul A. Dhavan,
• Rahul D. Kaduskar,
• Loana Musso,
• Leonardo Scaglioni,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2016, 12, 1624–1628, doi:10.3762/bjoc.12.159

• DIBAL-H gave the corresponding primary alcohol, which was converted into bromide 5 by Appel reaction with PPh3 and CBr4. The phosphonium salt obtained from this bromide was subjected to a Wittig reaction with nonanal, to afford compound 6 [12]. Attempts to remove the PMB protecting group (CAN, DDQ, TFA

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• –Smith method [13] as illustrated in Scheme 3. For further elaboration, aldehyde 15 was reduced with NaBH4 in good yield to generate the corresponding benzyl alcohol 19 [14]. Iodination of 19 to generate 20 with HI in chloroform [15] proved superior (95% yield) to the more classical Appel protocol which

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• considered because it is highly prevalent malignancy and on the second place in the list of cancer-related deaths due to its high metastatic potential [31]. Results and Discussion Chemistry Cholest-5-en-3β-ol (1) was activated as bromide in very good yield under Appel conditions [32], which means treatment

Polythiophene and oligothiophene systems modified by TTF electroactive units for organic electronics

• Alexander L. Kanibolotsky,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2015, 11, 1749–1766, doi:10.3762/bjoc.11.191

• -deficient acetylene compounds (Scheme 6). By reacting 23 with 24a this method provides diester 25a in good yield [63]. Compound 25a can be reduced to diol 25d [64] and further converted by either the Appel method [59] or by reaction with PBr3 [65] into dibromomethyl compound 21, which is required for

Discrete multiporphyrin pseudorotaxane assemblies from di- and tetravalent porphyrin building blocks

• Mirko Lohse,
• Larissa K. S. von Krbek,
• Sebastian Radunz,
• Suresh Moorthy,
• Christoph A. Schalley and
• Stefan Hecht

Beilstein J. Org. Chem. 2015, 11, 748–762, doi:10.3762/bjoc.11.85

• then converted in dibromide 19 by an Appel reaction. Macrocyclization of 19 with 3,4-dihydroxybenzaldehyde under “pseudo high-dilution” conditions, i.e., slow addition of the two reactants into a solution of Cs2CO3 in DMF at 100 °C provides the corresponding crown ether aldehyde 20. Porphyrin synthesis