Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• -workers developed chiral amine 1 with an electron-deficient iodine atom, which catalyzed the Mannich reaction in excellent yields and enantioselectivities [17]. In 2020, Huber and co-workers reported the bis(iodoimidazolium) 2-catalyzed Mukaiyama–aldol reaction of carbonyl compounds with enol silyl ethers

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

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• approach would conceptually differ from previously reported anodic syntheses of cyclic diaryl iodonium compounds, where an electrochemically generated acyclic iodine(III) intermediate undergoes an intramolecular SEAr-type reaction to form the cyclic product [19][20]. Herein, we report on the development of

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• converted with enaminones to 3-sulfenylchromones under iodine catalysis, an attempt was made to see whether this reaction system would be suitable for this reaction. Fortunately, the target products could indeed be obtained in high yields under these reaction conditions. Based on the optimized conditions

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• target products in good to excellent yields. Mechanistic studies revealed that the reaction proceeds via a radical pathway. Keywords: cyclization; difluoromethylation; hypervalent iodine; polycyclic imidazole; visible light; Introduction Organofluorine compounds continue to play important roles in

• reaction (Table 1). Employing PIDA as the promoter, THF as the solvent, and 72 W white LED as the light source, the desired product 3a formed in 85% isolated yield at room temperature (Table 1, entry 1). We found that the hypervalent iodine reagent was of significant importance for the present

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• employing electricity as an oxidant (Figure 11) [60]. Mechanistic studies have indicated that n-Bu4NI acts as a redox mediator at the anode, and the electron transfer between the copper complex and the iodine radical is the rate-determining step. The author proposed a catalytic cycle, as illustrated in

• Figure 11. Initially, the Cu(II) catalyst 50 coordinates with substrate 47 and amine electrophile 48 to generate Cu(II) intermediate 51, which is then oxidized by the iodine radical to form Cu(III) complex 52. Cu(III) complex 52 undergoes electron transfer to produce radical cation intermediate 53

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• two steps from 1,8-DHN (19) [57]. Methoxymethyl (MOM) protection of free -OH group of 29 using NaH and MOMCl afforded MOM-protected naphthol 30 in excellent yield (96%) [58][59]. It is worth highlighting the structural differences of naphthalenes 25 and 30, where the halogen (iodine) is on the same

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

• Beatriz Dedeiras Catarina S. Caldeira Jose C. Cunha Clara S. B. Gomes M. Manuel B. Marques LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, NOVA FCT , 2829-516 Caparica, Portugal 10.3762/bjoc.20.272 Abstract The reactivity of our recently disclosed hypervalent iodine

• . A plausible mechanism is proposed, suggesting a possible radical pathway. Keywords: electrophilic amination; hypervalent iodine reagents; sulfinamide; sulfonamide; Introduction Iodine(III) compounds, known as λ3-iodanes, have been extensively applied in organic synthesis. Although initially used

• as strong oxidizing agents [1], during the last decades HIRs have been investigated as group-transfer reagents, useful in several bond-forming reactions, such as in C–C, C–N, and C–O [2][3][4][5]. The benziodoxol(on)e family, cyclic iodine(III) reagents, stands out for their thermal stability and

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• 10.3762/bjoc.20.263 Abstract A novel study on the hypervalent iodine-mediated polyfluoroalkylation of sulfoxonium ylides was developed. Sulfoxonium ylides, known for their versatility and stability, are promising substrates for numerous transformations in synthetic chemistry. This report demonstrates the

• reactants. Finally, DFT calculations provided insights about the mechanism of this transformation, which strongly suggest that an SN2 reaction is operative. Keywords: alkylation; DFT calculations; fluorine chemistry; hypervalent iodine; sulfoxonium ylide; sulphur ylides; Introduction Introducing fluorine

• research groups recently reported the α-arylation between sulfoxonium ylides and diaryliodonium salts [33], and encouraged by this precedent, we envisioned that the chemistry between sulfoxonium ylides and hypervalent iodine compounds might be ripe for further exploitation. The trifluoroethyliodonium salt

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• can be noticed that the presence of an amino acid is compatible with the conditions of the reaction and did not interfere or significantly decrease the yield of the reaction (Scheme 3). Then, the N-carboxylate hydrazides 5a–d were firstly oxidized with iodine in the presence of potassium carbonate to

• lead to the corresponding hydrazones 6a–d in good yields (69–80%). Surprisingly, these conditions were unsuitable for compounds 5e and 5f and led to the formation of numerous byproducts. Fortunately, the replacement of iodine with N-bromosuccinimide (NBS), previously reported for the oxidation of

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• Charu Bansal Oliver Ruggles Albert C. Rowett Alastair J. J. Lennox University of Bristol, School of Chemistry, Bristol, BS8 1TS, UK 10.3762/bjoc.20.258 Abstract The chemistry of hypervalent iodine (HVI) reagents has gathered increased attention towards the synthesis of a wide range of chemical

• ; heterocycles; hypervalent iodine; oxidation; Introduction Halogenated carbocyclic and heterocyclic compounds are present in many active pharmaceutical ingredients [1][2]. The intramolecular halocyclisation of alkenes mediated by HVI(III) reagents allow access to a range of halogenated cyclic scaffolds in a

• this review aims to fill. The synthetic uses of HVI reagents [14][15][16], their involvement in heterocycle synthesis [17][18][19], and alkene functionalisation [20][21], have each been well-reviewed elsewhere. Review Hypervalent iodine-mediated fluorocyclisation Fluorine can substantially improve the

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

• intermediate C with tert-butylperoxy radical B leads to the target product 38. Pathway II involves the oxidation of TBAI with TBHP to form hypervalent iodine compounds D and E. The reaction of species E with substrate 37 leads to the formation of intermediate F, which interacts with TBHP to yield product 38

• . There is no consensus on the nature of the iodine species formed in reactions when using iodine-containing agents and their role in the mechanism of peroxidation. The selective peroxidation of malonodinitriles and cyanoacetic esters 39 with TBHP under Cu-catalysis without oxidative destruction was

• further attacked by TBHP to give product 61. Benzyl alcohols 62 were also converted into tert-butyl perbenzoates 63 under the action of the TBAI/TBHP system (Scheme 22) [65][66]. During the process, TBHP oxidizes TBAI into iodine, which reacts with the second TBHP to generate tert-butylperoxy radical B

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• Andrew Greener Stephen P. Argent Coby J. Clarke Miriam L. O'Duill School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK 10.3762/bjoc.20.245 Abstract Hypervalent iodine(III) reagents have become indispensable tools in organic synthesis, but gaps remain in the

• and potential decomposition pathways will enable the future design and development of new reagents. Keywords: hypervalent iodine; reagent development; structural analysis; thermal stability; thermogravimetric analysis; Introduction Hypervalent iodine(III) reagents have experienced a renaissance in

• enable access to chemical motifs that are difficult to synthesise using traditional approaches. However, gaps remain in the functionality they can transfer. Specifically, unstabilised alkyl groups are still underrepresented. For the development of new hypervalent iodine reagents to bridge this gap, it is

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• arylation; rearrangement reaction; Introduction The chemistry of hypervalent iodine compounds is well-established and they are prevalent as oxidants and electrophilic reagents in organic conversions [1][2][3]. They have gained significant attention due to their high reactivity and ability to carry out

• various useful transformations under mild, eco-friendly reaction conditions [4][5][6][7][8][9][10][11]. Various review articles [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] and books [27][28] have appeared on the chemistry of hypervalent iodine compounds. In the past two decades

• , diaryliodonium salts (DAIS), a versatile category of hypervalent iodine compounds, have seen significant progress in hypervalent iodine chemistry. Their efficiency and environmentally friendly characteristics have positioned DAIS as next-generation arylation reagents [29][30]. Other than aromatic electrophiles

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

• intermediate C which underwent extrusion of iodine and dipropyl disulfide to give intermediate D. Subsequent reaction with acetic anhydride, pyridine and KHF2 resulted in the replacement of the TMS by acetyl groups which was important for practical reasons (stability during chromatography). The reaction of 13

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• (DMDS, 50 µL) and a 0.24 M iodine solution in diethyl ether (5 µL). The mixture was allowed to stand sealed at 40 °C for 15 h. Subsequently, the mixture was diluted with pentane (200 µL) and washed with a saturated sodium thiosulfate solution. The organic phase was dried over sodium sulfate and

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

• ]. This mild method proceeds with a broad range of unactivated alkenes, including natural products and pharmaceutical derivatives such as sulbactam acid and oxaprozin. Mechanistic studies revealed that the reaction was initiated by the electrochemical oxidation of iodide ions, generating iodine radicals

• that dimerize to form iodine (I2). Subsequent anodic oxidation of in-situ formed Et3N produced an α-amino radical. The iodine then reacts with the alkene to form an iodonium intermediate, which undergoes intramolecular cyclization with losing an electron, and a second water attack to yield the desired

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• Pierre Angot, 64053 Pau Cedex 09, France School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire ST5 5JX, United Kingdom 10.3762/bjoc.20.209 Abstract A change in mechanism was observed in the hypervalent iodine-mediated cyclization of N-alkenylamides when the carbon chain between

• , reaction conditions were developed, and the scope of this cyclization studied. Keywords: cyclization; DFT; hypervalent iodine; mechanism; proline; Introduction Proline is one of the 20 DNA-encoded proteinogenic amino acids that are essential to life [1][2]. In addition, the pyrrolidine core is present in

• enantioselective conjugate addition to α,β-unsaturated pyroglutamic acid derivatives followed by deoxygenation [10], and the enantioselective organocatalytic reaction between 2-acylaminomalonates and α,β-unsaturated aldehydes [11][12]. The development of new synthetic methods using hypervalent iodine reagents has

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• depending on the incorporated halogen on the pyran core at C4: −208.33 ppm for 12 (fluorine), −197.95 ppm for 13 (chlorine), −192.80 ppm for 14 (bromine), and −184.56 ppm for 15 (iodine). Similarly, the increase in chemical shift of F2 is smaller as exemplified with an upfield shift of −205.46 ppm for 12 to

• includes effective core potentials for iodine. Empirical dispersion was accounted with Grimme’s D3 [72][73] correction including Becke–Johnson damping [74]. Computations were performed both in the gas phase (i.e., individual molecules with thermal corrections at 298.15 K based on ideal gas assumptions) and

• , 17, and α-ᴅ-talose 18. ORTEP diagram showing 50% thermal ellipsoid probability (except for 18): carbon (gray), oxygen (red), fluorine (green), chlorine (orange), bromine (dark red), iodine (purple), and hydrogen (white). Packing arrangement of compound compound 15; a) View down the b axis; b

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• . Finally, the potential as halogen-bonding activator was benchmarked in solution in the gold-catalyzed cyclization of a propargyl amide. Keywords: diaryliodonium; gold catalysis; halogen bonding; hypervalent iodine; non-covalent interactions; Introduction The compound class of diaryliodonium (DAI) salts

• organocatalysis, previously only iodine(I)-based Lewis acids had been applied. However, after this study, the application of DAI salts as XB donors gained increasing interest and was investigated by several groups [11]. In the last years, important information about structure–activity relationships was also

• applied as catalyst for the cyclization of propargylic amide 11, a typical benchmark reaction in gold catalysis (Scheme 2) [24][25][26][27], which had previously already been activated by iodine(I) and iodine(III)-based XB donors [15][18]. To evaluate the activity of the new iodoloisoxazolium 7BArF, it

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• Phong Thai Lauv Patel Diyasha Manna David C. Powers Department of Chemistry, Texas A&M University, College Station TX, 77843, USA 10.3762/bjoc.20.197 Abstract Iminoiodinanes comprise a class of hypervalent iodine reagents that is often encountered in nitrogen-group transfer (NGT) catalysis. In

• the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis. Keywords: aziridination; electrochemistry; H-bond activation; hypervalent iodine; nitrene transfer; Introduction Hypervalent iodine reagents find widespread application in selective oxidation chemistry due to

• the combination of synthetically tunable iodine-centered electrophilicity and the diversity of substrate functionalization mechanisms that can be accessed [1][2]. Large families of iodine(III)- and iodine(V)-based reagents have been developed – including iodobenzene diacetate (PhI(OAc)2, PIDA

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• methods. For these reasons, it is no exaggeration to say that radical reactions of group 17 interelement compounds with isocyanides have hardly been developed. Upon exposure to near-UV light, perfluoroalkyl iodides (RFI) undergo homolysis to form perfluoroalkyl radicals (RF•) and iodine radical (I•). The

• perfluoroalkyl radical, as a carbon radical, rather than iodine radical can add to isocyanides to form imidoyl radicals. Then, the iodine atom of RFI can trap the imidoyl radicals to give the corresponding 1,1-adducts (R–N=C(I)–RF) in good yields [25][26]. Radical addition of group 16 compounds to isocyanides In

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• solvents (DES) [83]. Catalysis can also be achieved using molecular iodine [84], AlCl3 [85], sodium ascorbate [86], and even solid-state and nanoparticle-mediated catalysts like CuO/ZrO2 [87], Fe3O4@Si@MoO2 [88], caspacin-cyclodextrin functionalized magnetite nanoparticles (CPS CD) [89], and Mg-Fe

• generated hydrazones were cyclized with simple ketones to pyrazolines. The oxidation to the corresponding 4-halo-substituted pyrazoles 69 can be achieved in a one-pot fashion by halogenation with iodine chloride or elemental bromine (Scheme 24) [102]. When cyclic ketones are used, fused products 70 are

• esters are tolerated in the method [113]. Starting from enaminone 86 functionalization, the hypervalent iodine compound 87 facilitates the introduction of a difluoromethanesulfonyl group in the copper(I) bromide-mediated consecutive three-component synthesis of difluoromethanesulfonyl-functionalized

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• of the iodide anion generated molecular iodine which reacted with 39 to furnish unstable hypoiodous anhydride 40, thereby triggering the key CO2 extrusion. The resulting C(sp2)-centered radical 42 underwent a SET anodic oxidation/cyclization/deprotonation sequence to yield the oxadiazole derivative

• 38. As such, the iodide electrolyte served as an electromediator to both promote the decarboxylation process and protect the aniline product from overoxidation. Importantly, a control experiment without electricity but in the presence of molecular iodine instead proceeded smoothly, thereby confirming

• the critical role of in situ-generated molecular iodine (Scheme 8) [44]. Formal cycloaddition Hydrazones constitute a versatile building block for the construction of azacycles through formal cycloaddition reactions. Under oxidative electrochemical conditions, either the oxidation of the hydrazone or