Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• for the synthesis of functional materials via cross-coupling reactions. Next, we extended our investigation to 1-naphthol in this reaction, and found that the arylation of 1-naphthol was achieved selectively at the C-2 position. The cascade cyclization resulted in the corresponding products 3an and

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

• 18 containing an exocyclic alkene was subjected to the reaction conditions, a mixture of benzylic chlorides (20) was formed in low yields, and trace amounts of the allylic chloride 19 was also isolated, the materials differentiated on the basis of the coupling of the acetal H5 with the respective

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• -sensitive substrates. Another challenge, shared with Nicewicz's method [90], is the preparation of arylacridine 159 in a single step from the relatively expensive 9-chloroacridine through Pd-catalyzed cross-coupling with 2-chlorophenylboronic acid. Additionally, for large-scale reactions, a flow reactor is

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• suitable for the coupling to peptides on resin, prepared by solid-phase peptide synthesis (SPPS) [35]. The detailed conditions for the amide-forming reaction were optimized using biscarboxylic acid-substituted C60 derivative 3 and a similar peptide with a primary amine derived from γ-aminobutyric acid

• a similar peptide (GABA-(Lys)5-peptide-PEG) on resin for the reaction with compound 3. Initial trials, using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and N-methylmorpholine (NMM), respectively, as a coupling reagent and a base, and 5 equiv of peptide on

• (32%) when HBTU was used as a coupling reagent. Finally, use of a greater excess (6.0 equiv) of peptide on resin relative to 3, and a combination of HBTU and DIPEA as the coupling reagent and base, provided the C60–peptide conjugate in an isolated yield of 41% (based on the used compound 3). The yield

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• properties and to modify the profile of biological activity due to optimum fluorine lipophylic properties, and enhanced interaction with lipid membranes [12][13][14]. Pentafluorophenyl-substituted porphyrin systems are especially useful for the connection of various functionalities capable for coupling with

• synthesis and characterization of tris(carboranyl)porphyrins of A3B-type (where “B” corresponds to the substituent responsible for bioconjugate coupling) based on the transformations of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin which was used as a basic compound for the synthesis of new boronated

• linkers capable to connect these porphyrins with biomolecules, thus improving their biomedical characteristics and theraputic efficacy for PDT and BNCT due to the combination of different substituents within porphyrin framework. Amide coupling of A3B-type carboranylporphyrin containing an amino

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• -workers developed an elegant chemoenzymatic route in 2000 [36]. The synthesis commenced to construct linear decapeptide 2 by global SPPS method on 2-chlorotrityl resin. After coupling 2 with N-acetylcysteamine (NAC, 3), the mimic of peptide-S-PCP, peptide-SNAC 4 was prepared. When incubated with purified

• limitations, such as possible Cα epimerization [45] during SNAC coupling and essential HPLC purification, which was generally difficult and time-consuming. Developing other different methods, exceptionally more straightforward approaches to access activated substrates, would solve this inevitable bottleneck

• TE-catalyzed marcolactonization [69]. The synthesis of linear peptide 34 commenced with the lactone opening of 26 to afford Weinreb amide 27. Following primary alcohol protection and amide reduction, the aldehyde 28 was coupled with iodide 29 to afford 30 via Nozaki–Hiyama–Kishi coupling, which was

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• with potential for further modification by cross-coupling. The full scope of the transformation can be found in Supporting Information File 1, Schemes S2 and S3 [45]. Concerning scope limitations, the azido-alkynylation of vinyl-pyridine 1b was unsuccessful and thiazole 1c only afforded 18% of the

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• diverse alkenes followed by a diradical coupling or radical addition process to achieve the difunctionalization (Scheme 1b, middle) [32][33][34][35][36][37]. However, to the best of our knowledge, the methodology involving the addition of a carbon radical from a diazo compound onto the double bond of an

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• 78.5 (C-4’), revealed the presence of a 2,4-di-O-methylpyranose substructure. Furthermore, an HMBC, δH 3.48 (H-6”)/δC 78.7 (C-4”), along with typical chemical shifts and coupling constants from C-1” to C-5” obtained in CD3OD (Table 2), indicated the presence of a 4-O-methylpyranose substructure. The

• HMBC, δH 3.64 (H-3’)/δC 103.0 (C-1”), indicated that these two sugar structures were connected through a glycosidic bond. The geometries of the two olefins at C-16 and C-20 were determined to be trans based on the large coupling constants, 3JH-16/H-17 15.0 Hz and 3JH-20/H-21 15.0 Hz, respectively. The

• geometry of the remaining double bond at C-18 was established to be trans by comparing the 13C NMR chemical shifts at C-16 and C-21 between 1 and polycavernoside D (5) (Table S1 in Supporting Information File 1) [5]. In addition, a 4J long-range coupling between δH 1.95 (H-26) and δH 2.18 (H-24) and three

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• cross-coupling between two aromatic rings [43]. In the future, further developments in bioinformatics, structural biology, and AI techniques will enable the design of biosynthetic enzymes and pathways to produce desired bioactive compounds, although understanding the chemistry catalyzed by individual

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• synthetic route, which enabled us to introduce a methyl substituent in this position. Likewise, methyl-substituted thiazolo[4,5-b]pyridines 5, 15a, and 15c were synthesized using an optimized Suzuki coupling and served together with compounds 12a–c as key intermediates to explore different reagents and

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• distance of 21 Å between the two Cu(II) complexes results in an independent paramagnetic behavior. However, in the closed form, the metal centers are much closer to each other (4.03 Å) resulting in a weak antiferromagnetic coupling via through-space exchange interaction. This demonstrates the value of

• coordination-switchable tweezers for switching between two magnetic states that are stable at room temperature [44]. To increase the magnetic coupling between the metal center the group investigated the Mn(III)–salphen tweezers 14 that can coordinate in apical position to cyanide ions. The complexation of CN

• − anions to the open form unexpectedly resulted in the closing of the tweezers thanks to a Mn–CN–Mn bridging [45]. An antiferromagnetic coupling between the two Mn(III) centers combined with a spin crossover from high spin to low spin Mn(III) was observed. Like in the other terpy-based tweezers, a

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• carbon, and one methyl carbon. A spin system H-6 (δH 6.85)/H-7 (δH 7.33) with an ortho-coupling constant (8.5 Hz) was observed using homonuclear correlation spectrometry (COSY). The heteronuclear multiple bond correlation (HMBC) cross-peaks from H-6 to C-2 (δC 112.4) and C-4 (δC 145.2), and from H-7 to C

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• , four methines (with one olefinic and two oxygenated), and four non-protonated carbons (with one olefinic and three bonded to oxygen). Detailed interpretation of the COSY spectrum of compound 1 revealed the presence of two discrete proton spin-coupling systems corresponding to a –CH–CH(OH)–CH2–CH2– unit

(E,Z)-1,1,1,4,4,4-Hexafluorobut-2-enes: hydrofluoroolefins halogenation/dehydrohalogenation cascade to reach new fluorinated allene

• Nataliia V. Kirij,
• Andrey A. Filatov,
• Yurii L. Yagupolskii,
• Sheng Peng and
• Lee Sprague

Beilstein J. Org. Chem. 2024, 20, 452–459, doi:10.3762/bjoc.20.40

• all cases, except the reaction in diglyme (Table 1, entry 5), a mixture of (E)- and (Z)-2-bromo-1,1,1,4,4,4-hexafluorobut-2-enes (3a,b) in a ratio of 2:1 was formed. The configuration of the isomers was determined by the 5JFFcis coupling constant in the 19F{H} NMR spectrum (ca. 0 Hz for (Z)-isomer and

• distillation in 52% yield for 6a,b and 34% yield for 7a,b. NMR analysis showed the mixtures of (E)- and (Z)-isomers in both cases with the ratio E/Z = ≈4:5 for 6a,b and E/Z = ≈1:2 for 7a,b. The configuration of the isomers was determined by the 5JFFcis coupling constant in the 19F{H} NMR spectrum (ca. 0 Hz for

• column 7a was isolated in 67% yield. The 19F{1H} NMR spectra of 7a, showed the coupling constant of CF3 and CF3 to be 11.3 Hz, suggesting strongly that product 7a like the original silane 8 has (E)-configuration. Although some olefins presented above were obtained several decades ago, there was almost no

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• arm in an adjacent peptidyl carrier protein (PCP). The amino acid loaded on the PCP then undergoes coupling with the amino acid loaded on the downstream PCP in the condensation (C) domain. Finally, the linear peptide on the PCP in the last module is either hydrolyzed or cyclized by a thioesterase (TE

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• palladium-catalyzed direct intermolecular arylation, followed by a direct intramolecular arylation step. As the C–H bond activation of several benzene derivatives remains very challenging, the preparation of fluoranthenes from 1,8-dibromonaphthalene via Suzuki coupling followed by intramolecular C–H

• contrast, only a few examples of fluoranthene backbone preparation by Pd-catalyzed C–H arylation have been reported. Some examples of the preparation of this skeleton by Suzuki coupling followed by intramolecular C–H coupling have been described [18][19][20][21][22][23][24]. In 2017, Metin, Türkmen and co

• intermolecular Suzuki coupling with an intramolecular C–H arylation, it should be possible to access numerous fluoranthene derivatives from commercially available 1,8-dibromobenzene in a single manipulation (Scheme 1d). Here, we describe i) conditions enabling the annulative π-extension of 1,8-dibromonaphthalene

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• not seen wide applications in nanocatalysis despite its numerous benefits. Therefore, Ozturk made it usable by coupling it with an ionic liquid, creating g-C3N4-SO3H nanoparticles, which displayed high catalytic activity for the Friedel–Crafts arylation of indoles with aldehydes. The optimum product

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• of parameters with which to control reactivity. In this perspective, we provide an overview of the different mechanisms for radical reactions involving NHPI esters, with an emphasis on recent applications in radical additions, cyclizations and decarboxylative cross-coupling reactions. Within these

• years and in the past, they were perceived as fleeting reaction intermediates. Recent progress in photoredox catalysis [6][7][8], electrochemistry [9][10], and the use of transition-metal (TM) catalysts in radical cross-coupling reactions [11] have dramatically expanded the use of radicals in synthesis

• ]. Two decades later, in 2012 the Overman group demonstrated the utility of this transformation in the total synthesis of (–)-aplyviolene, involving the diastereoselective coupling of a tertiary radical and an enone acceptor [38]. Further developments of this chemistry resulted in the general use of NHPI

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• probes, organic light-emitting diodes, and organic solar cells [2][7][8][9]. The principal way for the preparation of these heterocycles involves the coupling of 3H-phenoxazin-3-ones with variously functionalized aromatic amines. This is followed by the cyclization of the initially formed adducts [10][11

• unpaired electrons and the singlet biradical form. In previous studies on the coupling of 3H-phenoxazin-3-one derivatives 8 and 9 with o-phenylenediamine [10][11], the preference was given to the 12Н-quinoxaline[2,3-b]phenoxazine form 7 (Scheme 5). A series of N-aryl derivatives of this form was also

• shifts were measured with a precision of 0.01 ppm, and 0.1 Hz for spin–spin coupling constants J. The assignment of resonance peaks was carried out using COSY, HSQC, and 1H,13C as well as 1H,15N HMBC. Melting points were determined using a PTP (M) apparatus and were left uncorrected. IR spectra were

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• corresponding boronic acid 9 and a Suzuki–Miyaura cross-coupling between 8 and 9 gave rise to dimer 10, followed by the oxidation of both acenaphthene units into 1,8-naphthalic anhydrides. Installation of the thiepine ring was achieved by a double nucleophilic aromatic substitution induced by sodium sulfide

• corresponding bis(thiophenyl) thioether, which then underwent successive bromination and iodination to give intermediate 18. Next, a two-fold Suzuki–Miyaura cross-coupling occurring chemoselectively on the iodinated positions allowed the symmetric extension of the hydrocarbon scaffold, with the insertion of two

• thiepine via a two-fold Suzuki–Miyaura cross-coupling with 1,2-phenylenediboronic pinacol ester. The resulting S-doped extended tribenzothiepine 21 proved stable under ambient conditions for several months and exhibited good solubility in common organic solvents, which is ascribed to the boat-shape

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

•  1), unveiled the following reaction mechanism: initially, an oxidative coupling of the two alkyne moieties of our model 1a leads to the formation of INT 1, as previously reported [33]. This step, with a Gibbs energy barrier of 25.7 kcal·mol−1, is the rate-determining step for this process. Next, INT

Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• regioselectivity. Significant advancements in the synthesis of arylthianthrenium salts have prompted a growing interest in their utilization as versatile precursors for the conversion of C–H bonds in arenes into C–C/X bonds through transition-metal-catalyzed cross-coupling processes [12][13][14][15][16][17][18][19

• -metal-catalyzed cross-coupling [32][33] and aminofunctionalization [34] of alkenes were achieved, benefiting from the unique reactivity of organothianthrenium species that are generated through the reaction of alkenes and thianthrene sulfoxide (TT=O) or thianthrene (TT) (Scheme 1b). Alcohols are widely

• accessible and have significant importance in the pharmaceutical industry, positioning them as appealing candidates for C(sp3) coupling due to their availability as a common chemical feedstock. However, due to the high bond dissociation energy of the C–O bond and the poor leaving ability of the hydroxy group

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• ) were measured. The significant difference in the quantum yield values between the compounds was attributed to the increase in the population of triplet excited states because of spin–orbit coupling by bromine atoms. On the contrary with previous studies, it was found that the effect of proton and

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• , leading to the formation of the α-phosphoryl GlcNAc-MurNAc-monopeptide derivative. Subsequently, coupling this intermediate with tetrapeptide, TFA·H-ʟ-Ala-γ-ᴅ-Glu(OMe)-ʟ-Lys(COCF3)-ᴅ-Ala-ᴅ-Ala-OMe under mild conditions resulted in the synthesis of dibenzyl α-phosphoryl GlcNAc-MurNAc-pentapeptide 7 (see

• Supporting Information File 1 for comprehensive information on the synthesis details of the tetrapeptide). To avoid loss of valuable material through HPLC purification, crude 7 is used directly in the next step, and purification performed after the final prenyl phosphate coupling and global deprotection

• . Finally, the benzyl-protecting groups in compound 7 were cleaved via hydrogenolysis, followed by co-evaporation of the resulting crude product in pyridine. This yielded a monopyridyl salt, setting the stage for the final lipid coupling and deprotection sequence. To establish the vital lipid diphosphate