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

• presence of transition metal catalysts [11][12][13][14]. Currently, this motif is synthesized by sequential introduction of the two functional groups [11][12][13]. Addition of a lithium acetylide to an epoxide affords the corresponding homopropargylic alcohol which can then undergo a sequence of mesylation

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• for 1 h with 10 mg/mL lysozyme. After 10% SDS was added to the tube, the mixture was incubated at room temperature, 60 °C, and then 0 °C, for 5 min durations. AcOK (5 M) and phenol/CHCl3/isoamyl alcohol (25:24:1) were then added, and the resulting solution was gently mixed by inversion and centrifuged

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

• , amoxapine, an ibrutinib derivative, N-desmethyl sildenafil, silodosin, and lapatinib (4d–k, 35–67%). The late-stage modification of these drug agents and their derivatives in this MCR underlined the synthetic value and high functional group tolerance (e.g., aromatic amine, amide, alcohol, heterocycle). We

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• , such as medium-chain alcohol dehydrogenase (CpDCS), esterase (CpDCE), P450 and O-methyltransferase (CpOMT1) (Figure S37). Through genome excavation and analysis of Penicillium shentong XL-F41, a significant difference was discovered between the key enzymes involved in the formation of product compound

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• of compound 4b has been confirmed by single crystal X-ray data. The next step was to investigate the possibility of obtaining six-membered oxygen-containing spiroheterocycles by interaction of DAS 1 with 2-(bromomethyl)benzyl alcohol (15) (Scheme 6). The synthesis was carried out under the conditions

• summarized in Scheme 8). The first pathway is realized in the formation of five-membered (in the case of 3-bromopropanol) and six-membered (in the case of 2-(bromomethyl)benzyl alcohol) cycles – the cyclization of the anion is faster than its reverse protonation. The same applies to substrates with activated

• alcohol followed by base-promoted cyclization. The procedures developed allow to obtain derivatives of such sought-after scaffolds in the field of medicinal chemistry as Δα,β-butenolides, tetrahydrofurans, and pyrans spiro-conjugated with a pyrrolidine ring. The tandem approach proposed is characterized

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

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• -withdrawing phosphines. A DCM/alcohol cooperative effect was quantified, and a continuum of isotope effects was measured with low KIE’s in the absence of deuterated alcoholic solvent, increasing to large solvent KIE’s when comparing reactions in pure MeOH to those in pure MeOH-d4. The effects are interpreted

• Lewis bases as additive to the bulk CH2Cl2 solvent (Figure 6) and compared them to the baseline rate in the absence of additive. The rates of formation of 3a are mildly sensitive to alcohol structure with MeOH outperforming EtOH and propanol. For the set of linear alcohols, the shorter the chain, the

• behaves accordingly here [66]. Specific gold–oxygen interactions are typically not invoked in mechanistic discussions, though a gold alcohol complex has been proposed in silyl enol ether protonation [67]. Equilibrium studies by Maier et al. indicate that methanol is more weakly coordinating than alkynes

(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

• 11 had an allene structure. It was also important to note that the reaction proceeded more selectively in ether, which significantly reduced the amount of byproducts. Pure final alcohol 10 was isolated by column chromatography on SiO2 in 46% yield and 1H, 19F and 13C NMR spectra were in full

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

• substitution with alcohol 94 in the presence of lithium phthalimide 95 leads to product 96 and turns over the catalytic cycle. Importantly, species 93 can be detected by high resolution mass spectrometry, when the reaction is carried out without nucleophile and using stoichiometric amounts of PTH1. H. Fu and

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

• Abstract In recent years, S-(alkyl)thianthrenium salts have become an important means of functionalizing alcohol compounds. However, additional transition metal catalysts and/or visible light are required. Herein, a direct thioetherification/amination reaction of thianthrenium salts is realized under metal

• -free conditions. This strategy exhibits good functional-group tolerance, operational simplicity, and an extensive range of compatible substrates. Keywords: amination; functionalization of alcohol; metal-free; S-(alkyl)thianthrenium salts; thioetherification; Introduction Sulfonium salts [1][2][3][4

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

• , followed by in situ re-acetylation of the C2-amino group and C6-alcohol with acetic anhydride, resulting in the formation of disaccharide 4 in a one-pot fashion. The anomeric benzyl protecting group in disaccharide 4 was then removed via a Pd/C-catalyzed hydrogenation reaction, producing a mixture of α/β

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

• enantioselectivity dropped significantly (Table 1, entries 9 and 10). To further improve the enantioselectivity of this CPA-catalyzed transfer hydrogenation, we next explored the effect of the alcohol part of Hantzsch esters (Table 2). The experimental results showed that the ee value of product 2a increased as the

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• inevitably change. This could lead to modifications of the structure of the corresponding supramers of reactants, hence their properties. Indeed, we have already addressed this issue and found that the stereoselectivity of the glycosylation of alcohol 3 by a related N,O-acetylsialyl thioglycoside may depend

• procedure The glycosylation procedure followed that described in our previous publications [33][36][37]. A mixture of thioglycoside sialyl donor 1 [36] or 2 (1 equiv, 0.1 or 0.15 mmol) and alcohol 3 [54] (1 equiv) was dried in vacuo for 2 h, then anhydrous MeCN (2.0 mL for 0.1 mmol of sialyl donor and 1.0

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• reaction is possible upon elimination of the resulting benzylic alcohol on D, allowing another arylation forming E [18]. This complex sequence of transformations is herein applied to the synthesis of 1-aryltetralines, analogues of cyclolignan natural products having important medicinal applications [19][20

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• -carbonyl-based Michael acceptors. Results and Discussion Synthesis During our endeavors to identify potent Lewis-base catalysts for the oxa-Michael reaction [13][14], the triarylphosphine 1 was tested in a model reaction (2 equiv allyl alcohol, 1 equiv acrylonitrile, 0.05 equiv 1). However, no conversion

• with allyl alcohol (in both cases using a molar ratio of 1:1.05 and dichloromethane as the solvent). While in the latter case only the starting materials were observed after 24 h at room temperature, the reaction of 1 with acrylonitrile turned yellow during the same time and exclusively yielded the

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• ). The cinchona amine 3 was prepared starting from the naturally occurring quinine [31]. The gained catalyst was demethylated using BBr3 to give alcohol 4. The demethylated cinchona amine was reacted with half-squaramide [9] 5, resulting in demethylated squaramide 6. A short and flexible linker was

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• . Thus, aiming at enhancing the catalytic activity, we performed some additional photocatalytic tests, upon the addition of different concentrations of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP). This alcohol has interesting physical and chemical properties, and, being well miscible with many organic

• solvents and with water, it has been used in a large variety of (electro)chemical reactions [53]. The hydroxy group of this alcohol has a pKa of 9.3 [54][55], so we can expect that it is a suitable proton donor for this kind of reaction. We performed the photocatalytic CO2 reduction by dissolving in 5 mL 1

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• indispensable role in drug discovery and design since the hydrogen atom can act as lipophilic hydrogen-bond donor and act as a bioisostere for the alcohol moiety [81][82][83]. Thus, many effective difluoromethylation strategies have been developed in recent years. Difluoroacetohydrazonoyl bromides were chosen

A series of perylene diimide cathode interlayer materials for green solvent processing in conventional organic photovoltaics

• Kathryn M. Wolfe,
• Shahidul Alam,
• Eva German,
• Fahad N. Alduayji,
• Maryam Alqurashi,
• Frédéric Laquai and
• Gregory C. Welch

Beilstein J. Org. Chem. 2023, 19, 1620–1629, doi:10.3762/bjoc.19.119

• film, but use of such alcohol-based solvents limits the types of organic materials to be used as CILs. With ethyl acetate as a processing solvent a wider range of organic materials can be developed and studied as CILs. Herein, we report on the design, synthesis, and application of four new CILs using

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

• dissolved initiators in the liquid phase during the process. A suspending agent, e.g., polyvinyl alcohol (PVA), is added to the system to prevent coalescence. The viscosity in suspension polymerization is low throughout the process which brings good heat transfer and temperature control, and therefore well

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• method, diverse β-alkoxy sulfides were synthesized without the need to any catalyst, or additive. The reaction proceeded through the formation of carbonium ion intermediate I, which underwent electrophilic addition of alcohol to provide product 152. In the meantime, N-(arylthio)succinimide 1 as a

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

• . Two complexes, 61 and 65 (see Scheme 21), were found equally efficient. The products were obtained in 95 to 99% yield and the range of functionalities tolerated included nitro, nitrile, ether, carbonyl, alcohol, and amine [35]. Gautier and co-workers studied the effect of the addition of aromatic N

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

• , Supporting Information File 1). The closest characterised terpene synthase with an amino acid sequence identity of 25% is the (1(10)E,4E,6S,7R)-germacradien-6-ol synthase from Streptomyces pratensis [33]. The recombinant enzyme efficiently converted FPP into one sesquiterpene alcohol whose electron

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

• alkenyl compounds, the vinyl ether function is characterized by a (Z)-configuration as shown in Figure 1. In addition, an acyl group is present on the secondary alcohol of the glycerol. This acyl group is constituted by a saturated or unsaturated lipid chain or, in the case of platelet-activating factor

• of the secondary alcohol produced 2.3. The primary alcohol was deprotected in acidic conditions to produce 2.4. The installation of the phosphocholine polar head group was achieved in two steps starting with the reaction of 2.4 with bromoethyl dichlorophosphate (2.5) to produce the phosphate

• derivative 2.6. The treatment of 2.6 with trimethylamine produced an ammonium salt. A treatment with silver carbonate was applied to remove any traces of bromide salts. Then, the secondary alcohol was deprotected by hydrogenolysis to produce 2.7 (lyso-PAF). Finally, the acetylation of the secondary alcohol

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• oxidative alkylation of cyclic benzyl ethers with malonates or ketones. Oxygen is used as a terminal oxidant at atmospheric pressure. The key intermediate of this oxidative coupling reaction is benzyl alcohol intermediate C (Scheme 4) [52]. The generation of N–O radicals from NHPI in the presence of oxygen

• coupling process. Initially, ether 64 interacts with tert-butoxyl radicals via hydrogen atom transfer reaction to generate radical A with release of tert-butyl alcohol. Subsequently, the radical A adds to the C=C bond of α-oxo ketene dithioacetal 107 to form radical B, which further reacts with Fe(III) to