Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• alkenes remains a commonly employed approach, yielding high yields for styrene derivatives (Scheme 4) [41][42][43]. The example by Theato is remarkable (Scheme 4A), who used HCl (gas) bubbled into neat alkene 13 for 5 hours, and obtained a relatively high yield of the monohydrochlorinated product 14 after

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

• high yield (72%) of the homopropargylic azide was reached. Full insights are given about the factors that were essential for the success of the optimization process. Keywords: alkyne; azide; hypervalent iodine; photoredox; trifluoroborate salt; Introduction Homopropargylic azides are important

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• , resulting in much better yields of the target monoadducts. Electrochemical measurements revealed that the functionalization raised the LUMO level of Li+@C60, leading to lower reactivity for the second addition. With this facile, selective, and high-yield approach for the derivatization of ion-endohedral

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

• IPrAuCl [35]. In arylative cyclisations incomplete reaction was seen with enyne 19 [8][37] but ynone 22 [39] afforded high yield of 24. A quantitative conversion was seen in the intramolecular arylative cyclisation of 25 where 13 outperformed IPrAuCl [36]. Conclusion An L-shaped NHC ligand motif, AImOx

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

• series. Likewise, 1,8-naphthyridines are easily accessed in high yield and on a multigram scale via Friedländer synthesis [18]. This was in clear contrast to the intermediate thiazolo[4,5-b]pyridines and the desired 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine that we wanted to access, with approaches to

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• activator of NBS, as was previously shown by the example of a very successful bromination of 6-methylquinoline at position 5 with a preparative yield of 74% [27]. Indeed, under the new conditions, we obtained dibromo derivative 15 in high yield without heating and subsequent purification (Scheme 7). The

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• -indolines was developed (Scheme 1c). With this method, a variety of chiral 3,3-difluoroindolines were synthesized in high yield and enantioselectivity under mild reaction conditions. Results and Discussion We conducted a preliminary exploration of the reaction using 3,3-difluoro-2-(phenylethynyl)-3H-indole

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• -dimethylanilino))prop-2-yn-1-ol (34) and TCNE in dichloromethane at room temperature yielded 35, which was characterized by a furan skeleton (Scheme 13) [116]. This transformation occurred through the intermediate formation of the corresponding TCBD with a high yield of 85%. Furthermore, when 35 reacted with

• toward rotaxane synthesis involves affixing stoppers at both termini substituents and threading a molecular thread through a macrocycle. In this threading–stoppering strategy, a mild yet high-yield reaction is required for the stoppering process. The [2 + 2] CA–RE reaction, which yields push–pull

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• , entries 2‒7) showed that the use of 100 mol % of DBU is optimal for the selective synthesis of triazole 3a in high yield (Table 1, entries 4 and 5). A study of the reaction medium revealed that common organic solvents are highly efficient for this cascade reaction (Table 1, entries 1‒11). Among the

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• two steps and readily entered the diazo transfer reaction with 4-nitrophenylsulfonyl azide (4-NsN3). The resulting diazo reagent 5 was produced in a high yield after undergoing straightforward chromatographic purification. The use of a Boc group at the nitrogen atom of the diazo imide significantly

• product 6b in high yield. The reaction with methyl pyrrole-2-carboxylate resulted in the isolation of only the C–H insertion product 9c in low yield. Similar reaction progress was observed in the case with imidazole, the product N–H insertion was observed only in trace amounts (according to NMR data of

• /lenalidomide precursor 10 with a high yield (Scheme 5). In the near future, after removal of the protective group, the biological profile of the compound obtained will be studied (i.e., antimyeloid activity, degradation of transcription factors IKZF1/2/3, antiangiogenic activity, and cytokine secretion), which

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• a thiol to a C–C double bond and was first reported in 1905 [80]. It is considered as a click chemistry reaction due to its high yield, stereoselectivity, rate, and thermodynamic driving force. Generally, the thiol–ene reaction is conducted under radical conditions, often photochemically induced [81

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• been found to be highly efficient catalysts in this transformation. Nolan and co-workers reported the catalytic activity of [Cu(IPr)Cl] in the hydrosilylation of carbonyl compounds to form silyl ethers in high yield [48][49]. A series of bis-NHC–copper complexes was synthesized and the compounds were

Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• high yield of α-cadinene (11) (Figure 3C and 3D), and GGPP and GFPP were not accepted as substrate. For verification of the GC–MS-based identification the product was isolated from a preparative scale incubation of FPP (80 mg, 185 μmol) to obtain pure 11 (1.3 mg, 6.4 μmol, 3.5%). Structure elucidation

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• acylimidazole 3a (Table 1, entry 5) as monitored by TLC analysis. The reaction was completed after 3 hours, meaning that the in situ-formed enolate needed 3.3 equiv of tropylium NTf2 (2a) to complete the reaction. By this route, the tandem product 3a was isolated in a high yield of 93% but without any

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• the NG precursor 39 by heating dialkyne 38 and tetracyclone 2, which led to two hexarylbenzene units connected by an oxygen linker. Upon treatment of 39 under Scholl reaction conditions (DDQ, TfOH), an oxa-[7]helicene containing chiral NG 40 was obtained in high yield [43]. Meanwhile, they enlarged

• )benzene through Co-catalyzed cyclotrimerization in a 45% yield. Then monoiodide NG 49 was obtained through oxidative cyclodehydronation in a high yield. From the heptagon-containing NG 49, Sonogashira coupling with p-tert-butylphenylacetylene (50) afforded 51 in a quantitative yield. Subsequent Diels

• with cyclopentadienone 2 generated compound 57. The final Scholl reaction of 57 afforded helical NG 58 in high yield. This folded NG 58 is composed of two HBC layers fused to a [10]helicene with an interlayer distance of 3.6 Å as determined by X-ray crystallography. Since the helicene was initially

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• afforded the Pbf-protected [23] phenylglycine derivative 10a in high yield and enantioselectivity, an almost racemic mixture of 10b was obtained from the corresponding (p-methoxyphenyl)boronic acid (2b, Scheme 2a). This decrease in enantioselectivity can be attributed to a faster racemic background

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

• excellent yield (ca. 90%). After heating 150 with triethylamine, 151 was isolated in high yield at ca. 100 g scale (Scheme 34). The preparation of methoxyiminostilbene 151 by Singh et al. [56] complements the earlier synthesis of Fuenfschilling et al. [32] which requires 151 as an intermediate (Scheme 35

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• polysubstituted derivative 21g was also functionalized in high yield (71%). Pleasingly, other metals have been also successfully applied for the trifluoromethylthiolation of aromatic derivatives by C(sp2)–H bond activation such as Rh(III) and Co(III)-based catalysts as depicted below. Rhodium catalysis: In 2015

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• and the phosphonate 126 leading to the cis-ester 127 in high yield. Reduction of the ester using DIBAL gave the allylic alcohol 114 which was submitted to an Ullmann coupling [59] with isovanillin (80) to give the corresponding diaryl ether 128. Further esterification [60] with S-acetylthioacetic acid

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• azide and alkyne groups in high yield and regioselectivity without using harsh reaction conditions. In recent years, this click protocol has been successfully employed in porphyrin chemistry to synthesize various triazoloporphyrins by attaching an azide or alkyne moiety to the periphery of the porphyrin

• molecular architectures featuring 1,4-disubstituted triazole units with high yield and higher regioselectivity. The click-inspired synthesis and photophysical properties of diverse triazole-linked porphyrin conjugates are discussed in this review. This review includes a number of recent and important

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• reduction steps were compatible to be coupled in one flow system obtaining 6-monoamino-6-monodeoxy-β-cyclodextrin in a high yield. Our flow method developed is safer and faster than the batch approaches. Keywords: azidation; continuous flow; β-cyclodextrin; H-cube; 6-monoamino-6-monodeoxy-β-cyclodextrin

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• ] cyclooctene 27 in very high yield. The final stages of the synthesis corresponded to the elaboration of the second cyclopentenone ring allowing access to ent-fusicoauritone (28) in 24 steps. 1.1.1.2 Strategy 2: Late-stage formation of the 8-membered ring: Ophiobolins belong to the family of sesterterpenoids

• 31 and oxazolidinone 32 (Scheme 5) [26]. Subsequently, compound 33 was converted in four steps into aldehyde 34 which was engaged in a coupling reaction with bromoketone 35 according to Utimoto conditions to furnish the A-C-D adduct 36 as a single stereoisomer in high yield. Of note, the Utimoto

• expected tetracyclic cyclooctane-bearing product 92 in high yield (86%). Of note, this cyclization occurred on a highly functionalized substrate. All the carbons of the cyclooctene ring were stereogenic, except the two of the double bond, and the precursor possesses both a hydrindane and a cyclopentane

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

• -azidocholest-5-ene (5) in high yield. The same product was recently obtained by direct dehydroxyazidation of cholesterol upon treatment with N-acetyl azidobenziodazolone (ABZ) and PPh3 in THF [19], Table 1. While synthesizing new potential biologically active probes with cholesterol scaffolds in the Port Said

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

• converted to 3 through a 6-step sequence involving reduction of the aromatic ring and oxidation of the enone to a dienone. The resulting dienone 3 underwent a key photoinduced santonin-like rearrangement in the presence of acetic acid, furnishing 4 in high yield. It should be noted that the group of Hiraoka

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• conditions gave the secondary side peracetylated 6 in a high yield. The selective deprotection of silyl groups, yielding compound 7, was also performed standardly using BF3O·Et2O. Our new procedure is based on the methylation of this acetyl-protected β-CD 7 using a DIPEA/methyl tosylate mixture without