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

• yields of the desired product 7 (ca. 15–32%) due to competing ring opening reactions of the 7-cyclopropyl group (Scheme 2). Clearly, a better procedure was required. A large number of electrophilic chlorinating reagents for the direct chlorination of aromatic rings have been reported [17]. Recently, Xue

A photochemical determination of luminescence efficiency of upconverting nanoparticles

• Baptiste Amouroux,
• Clément Roux,
• Jean-Claude Micheau,
• Fabienne Gauffre and
• Christophe Coudret

Beilstein J. Org. Chem. 2019, 15, 2671–2677, doi:10.3762/bjoc.15.260

• (Figure 1) [25][27]. Switching of such diarylethene dyes in both directions (ring closure/coloration or ring opening/discoloration) by UCNPs has been documented for years, with a seminal work reported in 2009 by the team of Branda [28]. In the following we will show how this photochromic compound can be

• used to give a reasonable quantitative estimation of the upconversion phenomenon. In particular, we will exploit the ring-opening reaction since only the closed form 1-c presents a good spectral overlap with the visible emissions of the Er-UCNPs. In order to achieve a “user friendly” quantitative

• , the value of the ring-opening QY Φco of actinometer 1 is taken as 0.02, using the calibration curve by Sumi et al. [26]. Monochromatic actinometry is typically ran in a continuously stirred reactor and relies on the following equation: where d[1-c]/dt is the rate of consumption of the DAE closed form

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• long-wavelength isomers, we have found that a second, distinct long-wavelength isomer is produced electrochemically. This different long-wavelength isomer arises from a difference in the regiochemistry of spirocyclic ring-opening. The structures of both long-wavelength isomers were ascertained by

• cyclic voltammetry and 1H NMR analyses, in concert with computational modeling. These results are compared to those for the symmetric parent PSHD, which due to symmetry possesses only a single possible regioisomer upon either electrochemical or photochemical ring-opening. Density functional theory

• photochromism results from a spirocyclic ring-opening or other isomerization which results in increased conjugation. Electrochromism is also of increasing materials relevance, e.g., for self-dimming automotive mirror and aircraft window darkening applications [6][7][8]. In electrochromic applications, the color

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• ring-opening process from the ring-closed photoisomer to the original ring-opened photoisomer. The photo fatigue resistance of Glyco-DTE was then examined at 550 nm via an alternate irradiation with UV and visible light at room temperature. The ring-closing/opening cycles of Glyco-DTE could be repeated

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

• open forms with rather low emission efficiency. The photoswitching kinetics was studied at several wavelengths with UV and visible light. New diarylethenes underwent ring-closure reactions by irradiation with UV light (365 nm, 405 nm), and the reversible ring-opening by irradiation with visible light

• that in the OF each benzothiophene unit (with aligning thiophene group(s)) contributes into absorption independently. It was confirmed that asymmetric compounds with “compact” structures can be transformed to the closed form with the same light as bulkier analogs (the latter featuring slower ring

• -opening reactions; see Table 2). Second, a bithiophene residue induces a red-shift of 30–35 nm in the absorption of the OF with respect to a mono-thiophene ring. The oxidized DAEs (OF) absorbed at higher wavelengths than the corresponding nonoxidized analogs (by ca. 20–30 nm), and a splitting of the band

Click chemistry towards thermally reversible photochromic 4,5-bisthiazolyl-1,2,3-triazoles

• Chenxia Zhang,
• Kaori Morinaka,
• Mahmut Kose,
• Takashi Ubukata and
• Yasushi Yokoyama

Beilstein J. Org. Chem. 2019, 15, 2161–2169, doi:10.3762/bjoc.15.213

• ring opening of the closed forms. Wavelengths of absorption maxima of the closed forms of photochromic triazoles. Absorption spectral data of triazoles and other related photochromic compounds. Kinetic data of thermal back reactions and aromatic stabilization energy of 1c–3c, 9c and 10c. Natural charge

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• ] cycloadditions. For the former, the reaction of an aminodiene with a triafulvene initially resulted in the formation of a [2 + 2] cycloadduct, and an energetically strained 4-membered ring inevitably undergoes subsequent ring-opening (Scheme 13a) [10]. During the [4 + 2] cycloaddition, the triafulvene could only

• temperatures, as well as low levels of cytotoxicity against mouse fibroblast 3T3 cells [191]. With these characteristics in mind, the outlook for these hydrogels having therapeutic applications is promising, with further optimisation [236]. Pentafulvenes have also been used to prepare monomers for ring-opening

• [190]. Preparation of hydrogels via Diels–Alder cycloaddition with fulvene-conjugated dextran and dichloromaleic acid-modified poly(ethylene glycol) [191]. Ring-opening metathesis polymerisation of norbornene derivatives derived from fulvenes and maleimides to furnish facially amphiphilic polymers

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• synthesis of new pyrrolidine nitroxides from 5,5-dialkyl-1-pyrroline N-oxides via the introduction of a pent-4-enyl group to the nitrone carbon followed by an intramolecular 1,3-dipolar cycloaddition reaction and isoxazolidine ring opening. The kinetics of reduction of the new nitroxides with ascorbate were

• -enylmagnesium bromide to the corresponding nitrone, oxidation to alkenylnitrone, intramolecular 1,3-dipolar cycloaddition, and isoxazolidine ring opening. Nitroxide 1 showed both an unexpectedly low reduction rate [6] and long relaxation times t1 and tm at room temperature [4]. Unexpectedly high resistance of

• performed for reductive isoxazolidine ring opening [15][16] producing aminoalcohols 9a–c in 85–95% yields (Scheme 2). We have previously reported that oxidation of secondary amines with a spiro(2-hydroxymethyl)cyclopentane moiety at the α-carbon with the H2O2/WO42− system is ineffective whereas conversion

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

• oxidation conditions. Based on this assumption, the corresponding silyl nitronate from 3-nitropropanal or its acetal were not tried for cycloaddition. We then set to liberate the β-hydroxy ketone synthon by ring opening of the isoxazoline 3 (Scheme 3). Raney-Ni-catalyzed hydrogenolysis in the presence of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• ring opening at the less substituted carbon and effective deoxygenation performed at the C2 substituent [39]. This strategy was applied in the formal synthesis of (R,R)-formoterol (14) and (R)-tamsulosin (15) (Scheme 5) which have been used as therapeutic drugs for many years [40][41]. They are

• aziridine ring opening combined with functionalization of the C2 substituent and optional alkylation or arylation of the nitrogen atom [44]. Following a similar regioselective aziridine opening, a mixture of epimeric amino alcohols (2R/S,1'R)-23 was prepared in two steps from the aziridine alcohol (2R/S,1'R

• compounds were obtained in a 84:16 ratio. The major ether (2R,1'R)-26, which emerged from the displacement of the tosyloxy group (path a), was accompanied by (2S,1'R)-26 which came from the aziridine ring opening at C3 (path b). After chromatographic purification and hydrogenolysis enantiomerically pure (R

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• –C bond formations, and ring opening reactions [83][84][85][86][87]. Along with these nickel and vanadium were also well known to catalyze a number of organic reactions. Recent reviews published on the catalytic applications of these metals in various forms have underlined the indispensable

A heteroditopic macrocycle as organocatalytic nanoreactor for pyrroloacridinone synthesis in water

• Piyali Sarkar,
• Sayan Sarkar and
• Pradyut Ghosh

Beilstein J. Org. Chem. 2019, 15, 1505–1514, doi:10.3762/bjoc.15.152

• sites along with H-bonding donor/acceptor site. So, it may also be associated to the nanoreactor to approach the enaminoketone. Then, consecutive cyclization and ring opening of isatin (translactamization) affords intermediate C which undergoes cyclocondensation to furnish the final product F

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• ] transferring the non-oxygenated boron substituent and promoting oxirane ring opening [39]. The group’s migratory aptitude cannot be directly compared to that known from cationic rearrangements, because the nature of the other boron substituents plays a key role in migration, as revealed by calculations [40][41

• B could be envisaged with the large pinacol substituent facing the small oxirane ring and thus placing the migrating group antiparallel to the adjacent oxiranyl C–O bond. This may explain the role of the diol substituent on the reaction efficacy (see Table 1). Upon migration and oxirane ring opening

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• -acyl-5-hydroxypyrazoline acts as a bidentate ligand [31]. Upon treatment with TMEDA mononuclear complexes with concomitant ring opening to give a seven-membered bidentate chelate are generated. Although numerous syntheses of pyrazolines [3][4][5] in general and 1-acyl-5-hydroxypyrazolines [24][25][26

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• ester ring opening, while compound 11 demonstrated to be stable. The two compounds showed no toxicity on human primary fibroblasts. Further studies will be conducted to determine the cellular uptake of compounds 8 and 11. Structure of boronic acid analogues (for clarity, sugar numbering has been

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• formed by a concerted pathway. Then the fluoride induced ring opening and subsequent cyclization of intermediate 84 would generate phthalimide 79. Although most multicomponent reactions leading to isoindolinones make use of benzoic acid derivatives as one of the starting components, in a few

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• Discussion Aliphatic polycarbonates are found in many biomedical applications since they have many desirable properties such as high biocompatibility, easy degradation, good mechanical properties, and low toxicity [21][22][23]. Many synthetic methods have been developed, and the chain-growth ring-opening

• biomedical applications [24]. The amidine base 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is one of the best studied and most popular organocatalysts for ring-opening polymerizations of cyclic carbonates and lactones [25][26][27]. In contrast to the high activity of lactone polymerization, cyclic carbonate

• improvement of reaction efficiency. The high impact collision energy [28][29] and exothermic nature of the given ring-opening polymerization [30] could increase the temperature of a ball-mill system, which would speed up the polymerization rate [31][32]. To gain insight into thermal effects, we monitored the

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• by epoxide ring-opening and esterification reactions with fatty acids 3 (Scheme 1). If successful, developing a multistep approach to prepare DAGs would contribute to the expansion of synthetic mechanochemical methodologies in ball mills [28][29][30][31], which are often limited to single-step

• hands, a selective epoxide ring-opening reaction with fatty acids 3 leading to the formation of the corresponding sn-1,3-protected monoacylglycerols (MAGs 4) was attempted (Scheme 3). Initially, commonly used solution-based protocols were tested in the ball mill [33]. For example, 2 was reacted with

• stearic acid (3a) in the presence of amines such as pyridine or tributylamine. However, the analysis of the reaction mixture only showed unreacted starting materials. In previous work, an acceleration of the oxirane ring-opening reaction with carboxylic acids [34] or alcohols [35] by using Lewis acid

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• by NMR, ESIMS, and X-ray crystallography. The utility of this chemistry is further demonstrated by the tests of the novel catalysts (up to 10−2 mol %) in different metathesis reactions such as cross metathesis (CM), ring-closing metathesis (RCM) and ring-opening cross metathesis (ROCM). Keywords: CM

• ; cross metathesis; Hoveyda–Grubbs catalyst; olefin metathesis; RCM; ring-closing metathesis; ring-opening cross metathesis; ROCM; ruthenium metathesis catalyst; styrene; 2-vinylbenzylamine; Introduction Ruthenium-catalysed olefin metathesis reactions have been playing an important role in various fields

• ][9][10][11][12], including most popular recent books [13][14]. Obviously, the application of various catalysts is required to achieve the best results in each of the many directions of metathesis reactions such as cross metathesis – CM, ring-opening metathesis – ROM, ring-closing metathesis – RCM

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• when the same sequence of diastereoselective carbometalation/oxidation was performed on cyclopropenyl ester 1, the in situ-formed donor–acceptor cyclopropanol undergoes a selective ring-opening to provide the acyclic product possessing a quaternary carbon stereocenter [57]. As the enantioselective

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• ciprofloxacin and moxifloxacin (Scheme 1), and reverse transcriptase inhibitors [2], such as nevirapine. Meanwhile, since 1 contains a three-membered ring with high tension [3][4][5][6] and a nitrogen prone to single-electron oxidation, ring opening readily occurs followed by N-centered radical formation. The

• (Rh2(II,II)), that efficiently catalyzes the ring opening of 1 to achieve cycloaddition with alkene substrates under an argon atmosphere [18]. During the reaction, no metal valence changes were observed. We proposed that Rh2(II,II) may coordinate with the nitrogen in 1 to decrease the bond dissociation

• 3,5-dimethyl compound 1d afforded the desired product 3d with an excellent yield of 91% (Table 2, entry 3). We reasoned the electron-withdrawing groups on the arene increased the nitrogen–hydrogen bond dissociation energy (BDEN–H) of compound 1 [21], decreasing the rate of ring opening. Substrates 1i

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• publication, catalyst 9 was used for an aqueous living ring-opening metathesis polymerization-induced self-assembly (ROMPISA). The authors demonstrated the possibility of performing living ROMP in water selecting a quaternary ammonium-based phenyl norbornene carboximide as core-forming monomer [60]. This

• tags. c) PEG-tethered catalysts. Chemical structure and components of amphiphilic molecule PTS and derivatives. In vivo metathesis with an artificial metalloenzyme based on the biotin–streptavidin technology. Most common metathesis reactions. Ring-opening metathesis polymerization (ROMP), acyclic diene

• metathesis (ADMET), ring-closing metathesis (RCM), ring-opening metathesis (ROM), and cross-metathesis (CM). Catalytic cycle for metathesis proposed by Chauvin. First aqueous ROMP reactions catalyzed by ruthenium(III) salts. Degradation pathway of first generation Grubbs catalyst (G-I) in methanol. Synthesis

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• more concentrated alkaline conditions (5 N KOH) as a result of a pyridinium ring opening–closure process [57]. It was also shown that the ionization of a diol fragment of NAD+ under alkaline conditions plays a very important role in the dissociative cleavage of the glycosyl bond of the “northern

Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• corresponding 1H-pyrrolo[3,2-c]pyridine-2,3-dione 4l. The most possible explanation of this fact is the steric hindrance introduced by the N-phenyl substituent, which obstructs the thiazole ring opening. Conclusion In summary, we have developed a novel approach to 1H-pyrrolo[3,2-c]pyridine-2,3-diones (5

Reusable and highly enantioselective water-soluble Ru(II)-Amm-Pheox catalyst for intramolecular cyclopropanation of diazo compounds

• Hamada S. A. Mandour,
• Yoko Nakagawa,
• Masaya Tone,
• Hayato Inoue,
• Nansalmaa Otog,
• Ikuhide Fujisawa,
• Soda Chanthamath and
• Seiji Iwasa

Beilstein J. Org. Chem. 2019, 15, 357–363, doi:10.3762/bjoc.15.31

• the catalyst leakage during the work-up. Synthetic transformations of 2d and 2f In order to demonstrate the advantages of products, further synthetic transformations of the cyclopropane products were investigated. A ring opening and direct amidation of the chiral cyclopropane-fused γ-lacton 2d using