Synthesis and reactivity of azole-based iodazinium salts

• Thomas J. Kuczmera,
• Annalena Dietz,
• Andreas Boelke and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 317–324, doi:10.3762/bjoc.19.27

• to iodide and bromide were performed giving the salts 10a and 10b in excellent yields [27]. A copper-catalyzed iodination gave the diiodinated product 11 in quantitative yield [42]. Finally, N-methylation of 5aa was performed, to yield the dicationic salt 5av in 56% yield without decomposition of the

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• uptake of continuous flow synthesis can also be seen in the development of less frequently exploited extraction technologies. This is the case for a multi-jet oscillating disc reactor (MJOD) [64], where a continuous flow iodination reaction was coupled with a telescoped continuous flow work-up section

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

• application scope, robustness, and selectivity [74]. Recently, an electrochemical NHPI/PINO-mediated benzylic iodination was achieved using lutidine or 2,6-di-tert-butylpyridine as bases with low nucleophilicity [89] (Scheme 10). When pyridine was used instead 2,6-disubstituted pyridines its N-benzylation by

• of ethylbenzene and CH-fluorination of aldehydes catalyzed by N-hydroxybenzimidazoles, precursors of corresponding N-oxyl radicals. Mixed hetero-/homogeneous TiO2/N-hydroxyimide photocatalysis in the selective benzylic oxidation. Electrochemical benzylic iodination and benzylation of pyridine by

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• deprotection of the silyl group was accomplished in the presence of potassium carbonate (K2CO3) and methanol to provide the terminal alkyne 5 in 96% yield in two steps. The iodoarene 8 [12][16] was facilely synthesized from sesamol (6) via methylation and iodination in an overall yield of 67%. With the

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• (Scheme 6); iodination with NIS, as previously described [29], gave lower yields. We first attempted the coupling with the terminal alkyne 19, anticipating the possibility of reducing the triple bond after coupling reaction. In agreement with literature precedents, we chose LiHMDS for deprotonation of 19

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• - and p-positions in the case of bromination as well as iodination (product 2b, 2d, 2h, 2k, 2s, 2w, 2ab, 2ag, etc. in Scheme 3). In some cases, the formation of negligible amounts of dihalo derivatives (3–5%) could not be avoided. Only for the attempted monobromination of unsubstituted phenol, the

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• cyanation of the resulted isoxazoles 8a–f to cyanides 9a–f using Me2C(OH)CN/(Me2N)2C=NH [29], their acid hydrolysis, followed by esterification of the resulting acids 9a–f with diazomethane. 4-Iodoisoxazoles 12a–f, necessary for the preparation of 3,4-disubstituted isoxazoles, were obtained by iodination of

• 11a,c,e–g with NIS/TFA [30]. The reaction of 11d gave the product of double iodination 12c. 4-Iodoisoxazoles 12a,b,d–f were transformed into 3,4-substituted isoxazoles 13a–g by Suzuki reaction using a published procedure with some modifications [31]. Isoxazoles 1, except for isoxazole 1a, were

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• azobenzenes with electron-donating substituents by electrophilic activation with NXS. Halogenation of azobenzenes with electron-accepting substituents Using the optimal parameters for the mechanochemical bromination and iodination of L1 [51], we investigated the halogenation of azobenzene substrates with

• PdII-catalyzed iodination of L6–8 was conducted with N-iodosuccinimide (NIS) as the iodine source. The reaction time for the iodination of L6 was the same as for the analogous bromination reaction (Table 2, entry 10). Iodination of L7 and L8 was completed within five and seven hours, respectively

• (Table 2, entries 11 and 12). Unlike bromination, iodination of L6–8 with NIS resulted in a mixture of the mono- and diiodinated products at the ortho positions of one or both phenyl rings (LnI-IV and LnI-V, Scheme 2 and Table 2, entries 10–12), as confirmed by NMR spectroscopy (Figures S104–S130 in

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• approach, 1 was mono-O-allylated to 2 under similar conditions reported previously for monobenzylation (Scheme 3) [50]. Iodination (3) and subsequent elimination of the iodide with zinc dust gave allylic alcohol 4 as a single enantiomer, which was esterified with Boc-protected glycine to allyl ester 5

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• delivered 3c in 53% yield (Scheme 6). In an alternative approach we tried to synthesize non-benzylated species 1a from methyl indol-2-ylacetate. Iodination at position 3 of the indole backbone in the presence of N-iodosuccinimide [45] followed by Ullmann cross-coupling with o-bromo-nitrobenzene [46] was

• expected to give non-benzylated 1a. However, iodination of methyl indol-2-ylacetate led to polymerization reactions involving the CH2 protons. In order to investigate the general viability of this synthetic way, we performed iodination at position 3 of ethyl indole-2-carboxylate, which does not contain

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• 2008, Bhanage et al. developed a novel methodology for the synthesis of alkyl iodides/nitriles using ruthenium tris(2,2,6,6-tetramethyl-3,5-heptanedionate) (Ru(TMHD)3) as the catalyst (Scheme 24) [47]. This catalyst was found highly efficient in the hydrogenation, iodination, and cyanation reaction of

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• . While anthranilamide (5) bromination with N-bromosuccinimide in acetonitrile at room temperature [29] furnished 2-amino-5-bromobenzamide (6a) in 78% yield, iodination of 5 with iodine in the presence of hydrogen peroxide in water [30] at 50 °C provided 2-amino-5-iodobenzamide (6b) in 89% yield. After

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• structural motifs to provide the functionalized pyridine and pyrrole derivatives. The functionalization reactions cover iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, alkylation, selenylation, sulfenylation, amidation, esterification, and hydroxylation. We also briefly

• -ylmethanamine and thiophen-2-ylmethanamine were reacted smoothly with NIS under standard conditions, while they did not react well with NBS. Notably, under the same reaction conditions, the desired products of the iodination and bromoniation reactions were trifluoromethylated monoiodopyrroles 37 and

• functionalizations of pyrrole derivatives, such as iodination, bromination, trifluoromethylation, azidation, carbonylation, arylation, and alkylation. The proposed mechanism generally involves two kinds of intramolecular cyclizations: one is 6-endo-dig cyclization to promote the formation of pyridine ring

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• be inspected from Scheme 7, our journey in this regard stem from the iodination of 2 using H5IO6/I2/H2SO4 in acetic acid–water solvent system to afford the desired triiodotruxene derivative 22 in 50% yield. Furthermore, Suzuki–Miyaura cross-coupling reaction of 22 with 4-formylphenylboronic acid (23

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• which was methylated using methyl iodide and lithium diisopropylamide (LDA) to produce (–)-81a in 84% yield. Desilylation of (–)-81a followed by tert-butyldimethylsilyl (TBS) protection of (–)-82a gave ester (+)-83. Compound (+)-83 was converted to (Z,Z)-(+)-84 by using iodination and a diimide

• Scheme 10. Subsequent stannylation followed by iodination converted compound (−)-82b to an inseparable 7:1 mixture of (E,E)-iododiene (+)-89a, and its 6-iodo isomer 89b in 60% yield. Compound (+)-89a was then subjected to Stille coupling with oxazole vinylstannane 24 using Pd(PPh3)4, CuI, and CsF in DMF

• 82% yield (83% ee). Subsequent free radical hydrostannation on (−)-98 produced (+)-99 as the major product of a 46:1 mixture of (Z/E)-α-stannylated geometric isomers. The purified vinylstannane (+)-99 underwent iodination stereoselectively with excess N-iodosuccinimide to give (−)-100, which was then

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• iodination and bromination of 10 proved to be more difficult than anticipated. For example, attempts to obtain the 3-iodo derivative 11 using I2/Cs2CO3 in dioxane [48], NIS in DMF [49], NIS/AgNO3 in acetonitrile [50], and NIS/TFA in DCM [51] failed completely or provided the desired product as a complex

• was prepared via the palladium-catalyzed reduction of the corresponding phosphate 17 [54]. Iodination and Sonogashira coupling, followed by acetylation led to the formation of the desired enynyl acetate 20. This compound was treated with 5 mol % Ph3PAuCl/AgSbF6 in DCM, and after 6 h, this afforded the

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• conjugation of the desired moiety. A C8-alkynyl-modified adenosine derivative was synthesized, reviving an old synthetic pathway for iodination of purine nucleobases. Silylation of the C8-alkynyl-modified adenosine revealed unexpected selectivity of the two secondary sugar hydroxy groups, with the 3'-O-isomer

• halide to iodine, taking into account that direct iodination of purines has been claimed being troublesome [26], although not impossible [27]. For C8-iodination of adenosine, first the hydroxy groups at the sugar moiety were protected with tert-butyldimethylsilyl (TBDMS) groups. The silylated nucleoside

• 2 was dissolved in THF and lithium diisopropylamide (LDA) was added, followed by iodine in THF. The reaction temperature was kept strictly between −70 and −80 °C to make sure that iodination proceeds without further side reactions (Scheme 1) [28]. Despite the fact that the exocyclic amino group was

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

• they are the most trustworthy strategies for direct functionalization of aromatic scaffolds [50]. As can be inspected from Scheme 18, monoiodosumanene 79 was obtained by gold-catalyzed iodination in the presence of N-iodosuccinimide (NIS). The mononitrosumanene 80 was achieved through the nitration

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

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• (Scheme 2). Cyclohexanone 4a has acidic hydrogen atoms that can facilitate the aromatization by modification, e.g., by iodination. In order to obtain further insights into this possibility, 4a was heated with deuterium oxide, but no change was observed. In contrast, the signals assigned to the protons in

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• crotonate (15) with 1-hydroxymethylbenzotriazole (16) generated methyl 2,2-dihydroxymethylbut-3-enoate (17) in 58% yield. Iodination and subsequent double displacement with sodium sulfide afforded methyl 1-vinylthietane-1-carboxylate (19) in 51% yield over two steps [34]. Compound 19 was used as an

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• , followed by iodination and phosphonate introduction by an Arbusov reaction. Alternative approaches were elaborated from olefinic C-glycosides, which were converted into the corresponding C-linked hydroxymethyl derivatives and processed to give the glycosyl methylphosphonic acid derivatives [18][19]. As the

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• 12 (Scheme 2) were prepared. The transformations leading to diarylethene cores 3 and 6 were carried out on a 10–100 mmol scale (Scheme 1). The iodination at positions 6 and 6' of benzo[b]thiophene residues has been reported [5][8]. Following those protocols, diiodides 5 and 8 were obtained in fairly

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• later stage the optical purity could be improved (see below). Diol protection gave dioxolane 14, which underwent Saegusa oxidation to afford enone 15. Subsequent α-iodination gave access to α-iodoenone 16, which could be stereoselectively reduced under Corey–Itsuno conditions to yield allylic alcohol 17