Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• metathesis between the formed propargylic derivative and an appropriate allylic alcohol promoted by the Grubbs second-generation catalyst, finally produced in high yield (85%) the intermediate diene 6, as an essential building block for the southern fragment (Scheme 9). Several other asymmetric transition

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• the reaction and it was found that the optimized proportions of syngas were 5 bar CO and 5 bar H2 (1:1, (Table 3, entries 8–13). Scaled-up experiment Noteworthy, when conducting the reaction at a larger scale (10 mmol), benzaldehyde was obtained with a high yield of 93%, indicating that our system

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• obstacle was overcome by using a modified Fieser work-up procedure to yield the aldehyde 6 in high yield, 78%. Then, aldehyde 6 was converted to the α,β-unsaturated trans-ester 7 through a Wittig reaction with the phosphorane synthon 8, which was derived from ethyl bromoacetate at 60 °C for 8 h in THF in

Direct borylation of terrylene and quaterrylene

• Haruka Kano,
• Keiji Uehara,
• Kyohei Matsuo,
• Hironobu Hayashi,
• Hiroko Yamada and
• Naoki Aratani

Beilstein J. Org. Chem. 2020, 16, 621–627, doi:10.3762/bjoc.16.58

• -substitution with high yield. To isolate a pure product, the solvent was removed, then the reaction mixture was passed through a silica pad with CH2Cl2, followed by reprecipitation from MeOH. The yield of 2,5,10,13-tetrakis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)terrylene (TB4) was 56%. Since insoluble

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• readily available, dialkyl phosphonates and alkenyl(aryl)iodonium salts can be combined to form enol phosphonates in high yield and excellent selectivity. Results and Discussion We started our studies by investigating the reaction between diethyl phosphonate 1a and styryl(mesityl)iodonium triflate (2a

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• a reducing agent in a mixture of water and ethanol as the solvent at 85 °C. In continuation, bistriazoles have been produced using 0.4 mol % of 45 and 10 mg sodium ascorbate as a reducing agent in an ethanol/water mixture at 85 °C. All triazole products were produced in good to high yield (Scheme 7

• 24 h to produce a precipitate that was gathered and washed with water and ethanol (Scheme 18). It should be noted that 5.0 mol % of the 3D graphene/Cu nanocomposite 87 were sufficient to generate a high yield of the desired products in EtOH/H2O (1:1) at 70 °C. To screen the recyclability of 87, the

Copper-catalyzed enantioselective conjugate reduction of α,β-unsaturated esters with chiral phenol–carbene ligands

• Shohei Mimura,
• Sho Mizushima,
• Yohei Shimizu and
• Masaya Sawamura

Beilstein J. Org. Chem. 2020, 16, 537–543, doi:10.3762/bjoc.16.50

• methoxy group (in L2), the enantioselectivity drastically dropped to −10% ee, while the yield remained 99% (Table 1, entry 2). Similarly, N,N'-dimesityl-NHC L3, which lacked an oxygen functionality in the N-aryl group, showed poor enantioselectivity (9% ee) with high yield (99% yield, Table 1, entry 3

• ). Thus, the hydroxy group of L1 was essential for the enantioselectivity by the catalyst. When the mesityl group of L1 was changed to a bulkier 2-Me-4,6-Cy2-C6H2 group in L4, the enantioselectivity was markedly improved to 90% ee, with a high yield (97%, Table 1, entry 4). A naphthol substituent on the

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• exhibits unusual properties in nucleophilic reactions. This reagent was obtained [30][31][32] in high yield and with high purity by a one-pot synthesis from divinyl sulfide [33][34][35] and selenium dibromide. The structure of compound 1 suggests the possibility of formation of both seleniranium 2 and

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• hexadentate compound 16 in 73% yield. The synthesis of 19 (Scheme 3B) was achieved in moderate to high yield, firstly, by reacting equimolar amounts of LiPHPh and 2-chloropyridine (17) to give (2-pyridyl)phenylphosphide 18. Secondly, compound 18 was bridged by reaction with a half molar equivalent of

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• regeneration of the α,β-unsaturated 2-acyl-1-methylimidazole moiety was performed in high yield and E/Z selectivity via a two-step protocol. The resulting Michael acceptor was then engaged in an ECA to afford the expected 1,3-dimethyl product in 69% yield and a good diastereomeric excess of 94% (Scheme 17

• addition of diethylzinc to crotonyl N-acyloxazolidinone [48]. The 1,4-product was also formed in high enantioselectivity (>98% ee) and high yield (91%). The same year, Pineschi et al. evaluated various α,β-unsaturated acyl derivatives for the copper/(R,S,S)-phosphoramidite L16-catalyzed addition of

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• were obtained in short reaction time, high yield and purity without the need of any solvent when allenylboronic acid pinacol ester was used, or using a minimal amount of acetone when potassium allenyltrifluoroborate was used. Keywords: boron compounds; microwave; propargylation; regioselectivity

• - and regioselective way. The corresponding products were obtained after a short reaction time in high yield and purity without the need of a solvent when allenylboronic acid pinacol ester was used, or using a minimal amount of acetone when potassium allenyltrifluoroborate was used. The method is simple

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• , mesylate (SP)-60, and alkenylphosphine sulfide (SP)-65 were subjected to the reaction with Lewis-acidic AlCl3 (Scheme 12). Rearrangement of the tertiary alcohol (SP)-17 proceeded very efficiently, affording the corresponding product in high yield. Unfortunately, the stereoselectivity of the reaction

• stereoselectivity. It was found that the P-stereogenic β-/γ-mercaptoalkylphosphine oxides underwent intramolecular cyclization to the corresponding bicyclic phosphine oxides with high stereoselectivity and high yield under mild reaction conditions. 1H NMR spectra of compounds 12 and 29. 13C NMR spectra of compounds

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• excess, (LR/substrate 2.5:1, toluene, reflux) the reaction was chemoselective toward the amide group, and compound 2a was obtained in high yield (93%), although the unreacted LR complicated the isolation and purification of the product. Lowering the molar ratio of the starting materials to strictly

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• diazotized and treated with 1,3,5-trimethoxybenzene to afford (E)-1-(3,5-dibromophenyl)-2-(2,4,6-trimethoxyphenyl)diazene (15) in high yield. Unfortunately, the following monocoupling step using (4-cyanophenyl)- or (4-methoxyphenyl)arylhydrazides turned out to be rather ineffective. The desired monocoupling

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• , when the ethoxycarbonyl group R3 was replaced by an acetyl substituent, the resulting substrate was successfully converted to 2w with a high yield. However, when the substrate bore a strong electron-withdrawing cyano group, the reaction was less efficient. and the product 2x was produced in a much

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• -(1,6)-Man, α-(1,5)-Ara, and α-(1,2)-Man was synthesized by AGA using three monosaccharide building blocks. The linear oligomannosides were readily assembled and isolated in short time and high yield under standard conditions. The introduction of a capping step after each glycosylation and optimized

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• of 5 with 11 (1.5 equiv) gave 6 in reproducibly high yield (ca. 95%) when performed on gram scale. However, when performed on larger scale (9.3 g), the reaction stalled after ca. 90% conversion and addition of extra catalyst Pd[(PPh3)2Cl2] and/or 11 failed to drive the reaction to completion. We

Formation of alkyne-bridged ferrocenophanes using ring-closing alkyne metathesis on 1,1’-diacetylenic ferrocenes

• Celine Bittner,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2019, 15, 2534–2543, doi:10.3762/bjoc.15.246

• monomeric ferrocenophane 2a in a high yield (93%). The signal for the terminal proton has vanished in the 1H NMR spectrum, and the 13C NMR spectrum only shows one signal at 79.6 ppm associated with the symmetric C≡C triple bond. The same high yield for compound 2a could be achieved in an identically

• propargylic compound was synthesized as well in high yield. The NMR data fit the results of Suitor et al. that were published only recently [93]. Unfortunately, the propargylic compound could not be characterised crystallographically as it only gave an orange powder upon different crystallisation techniques

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• -nitrobenzaldehyde (8a) to give the corresponding tertiary amine 9a in high yield. The nitro group of 9a was subsequently reduced by SnCl2 in high yield. The resulting aniline 10a was used to obtain the azo compounds 12a–e in varying yields through a Mills reaction with the corresponding nitroso compounds 11a–e

• , which were commercially available or prepared as described in our previous communication [7]. A final methylation of the tertiary amine 12a–e with MeI in DCM and subsequent precipitation with MTBE (methyl tert-butyl ether) gave 2a–e as orange powders with ≥99% trans-isomer in moderate to high yield

• . proceeding through a tert-butylimine intermediate (31) formed under Dean–Stark conditions [32]. This imine was reacted with NaOiPr to form the ether 32, which was subsequently hydrolyzed to obtain the desired aldehyde 28g in high yield. Reductive amination of the aldehydes 28f–h with 7 furnished amines 16f–h

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• . In our control experiment, alkyne 2 was converted into product 4 in high yield (88 %) using AgOTf at 5 mol % (Table 1, entry 1). Interestingly, 1-methoxyisochromene 4 can also be isolated in 89% yield, using a AgOTf catalytic loading of 1 mol % (Table 1, entry 2). All silver complexes 1a–d (1 mol

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• subtilis of 9 µM and 10 µM for Micrococcus luteus, respectively [25]. For the sustainable, high yield production of bioactive diterpenoids various aspects have to be considered. One key issue in yielding high recombinant terpene production titers, are metabolic bottlenecks in the precursor supply, which

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• the use in multimodal (PET/OI) medical imaging of mitochondria in cancerous cells. Results: A dihalogenated fluorinatable pyridinyl rhodamine could be successfully synthesized with the high yield of 85% by application of a halogen dance (HD) rearrangement. The near-infrared dye shows a quantum yield

• rearrangement. By our optimized procedure, we have obtained the dye 15 at high yield and without the necessity of HPLC purification. The chlorine atom in 2’-position can potentially be used to introduce the PET radionuclide fluorine-18 while the bromine atom serves as a constraint against rotation around the

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• 6,7-difluoro-4-quinolone-3-carboxylate building block 10 was accessed in high yield in only three steps from commercially available substrates. The nature of the cyclopropanation–ring expansion makes the 4-chloro-3-carboxy-quinoline structure with perfect positioning of the carboxylate and chlorine

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• include the regioselective dihydroxylation and etherification to introduce the C-14 hydroxy group and the construction of the butenolide moiety. Particularly, the characteristics of Li’s route are low cost, high yield (9 steps, 44% yield) and easy handling (all intermediates could be scaled up to 100

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• triisopropylsilyl nitronate. Then, the catalytic asymmetric cycloaddition gave the 2-isoxazolidine cycloadduct 1 in a high yield. In the light of our previous ligand screening results [49], two bisoxazolines with an isopropyl (ligand B) or tert-butyl group (ligand A) were tested. Optimization of the conditions