Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• three generalisations [81]. Firstly, errors and kinetic traps are minimised by weak interactions of the assembly units. The weak interactions result in nucleation, the second generalisation, where the initiation of capsid formation is minimised. This in return reduces the kinetic trap. Finally, the

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• three alkyne derivatives were tested in the reaction, with yields ranging from 3% to 85%. Keywords: amine-borane complex; pentafluorosulfanyl chloride; pentafluorosulfanyl substituent; radical addition; radical initiation; Introduction The pentafluorosulfanyl (SF5) substituent has been attracting its

• styrene [48][49][50]. We envisioned that it could be possible to replace the Et3B in Dolbier’s protocol by a stable amine–borane complex that could perform the radical initiation of SF5Cl on its addition on alkenes. This would address the drawbacks associated with the use of Et3B as the radical initiator

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• the metathesis mechanism: i.e., whether a double (ene-then-yne mechanism) or a triple (yne-then-ene mechanism) bond first enters the initiation step of the precatalyst activation. The group 6 metal-based precatalysts prefer the latter mechanism and yield the endo-products, while Ru precatalysts enable

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• inefficient initiation step (i.e., Φinitiation << 1) (Equation 1). A less common use of quantum yields by organic synthetic chemists is as a measure of how efficiently the reaction uses the light source. Considering photocatalysis is often purported as a green chemistry because it uses light, a more efficient

• 1 with amine catalyst 3 to give enamine intermediate 4. The initiation step is proposed to be a reductive quench of the photocatalyst using 4 as a sacrificial reductant to give [Ru]•−, which can then reduce 2 to give electrophilic radical 2•. Addition of 2• to another molecule of 4 generates α-amino

• likely operates via a radical chain mechanism. Initiation begins with the reductive quenching of the photocatalyst using iPr2NEt as a sacrificial reductant to give [Ru]•−, which then reduces the Lewis acid-coordinated enone 271 to give alkyl radical 271•. In the presence of a second enone 270 and chiral

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• IUPAC as follows: “Change in the rate of a chemical reaction or its initiation under the action of ultraviolet, visible or infrared radiation in the presence of a substance – the photocatalyst – that absorbs light and is involved in the chemical transformation of the reaction partners” [90]. In

Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions

• Edgar Peris,
• Raúl Porcar,
• María Macia,
• Jesús Alcázar,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159

• enhanced precatalyst preparation, stabilization and initiation, PEPPSI) [23][24]. In addition to pyridine ligands, other compounds with coordinating atoms such as C, N or P have been reported to tune the catalytic activity of the NHC–Pd complexes [25][26][27][28]. Thus, a ligand containing P as the

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• then kept constant or slightly decreased. The possible initiation of the polymerization is presented in Scheme 11, where hydrogen bonding of 36 with water is crucial. In 2013, Wang and co-workers also reported the use of aliphatic ketones and aldehydes as photoinitiators for the photopolymerization of

• -one, as well as formaldehyde (35), efficiently initiated the polymerization of MAA (42), and butanone was the most efficient compound. Since acrylates and methacrylates can be photopolymerized by self-initiation, a blank experiment without the use of any aliphatic ketone 44 or formaldehyde (35) was

• carried out, indicating that the polymerization of MAA (42) was mainly induced by photoinitiation by the aliphatic ketones 44 or formaldehyde (35), rather than by self-initiation of the monomer. Furthermore, oxygen was shown to strongly inhibit the photopolymerization, and an increase in the UV intensity

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• conjugate acid needed for initiation. Thus, the higher the concentration of PA, the higher the conversion. Figure 3 nicely documents this scenario. In 2019, the first report about NIR-sensitized cationic photopolymerization appeared in combination with a high intensity NIR LED [65]. Such a combination

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• . Several proposal for the mechanism are found in literature ranging from a closed photoredox catalytic cycle [53][61] to a chain propagation mechanism with photoredox initiation [65]. We evaluated the reference NDI 1 and the cNDI 6 as new photoredox catalysts using this benchmark reaction. The samples were

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

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

• polymerization reached over 90% conversion after 2 h (Table 1, entries 10 and 11). While the reaction rate was higher than that of the solution reactions, polydispersity under ball-milling conditions remained low (Mw/Mn = 1.15). To maintain low polydispersity, fast initiation and slow propagation are required

• [28]. In the case of ball-milling polymerization, the time required for the physical mixing of monomer, catalyst, and initiator would result in a delayed initiation of the polymerization. However, the relatively slow propagation rate of DBU-mediated trimethyl carbonate polymerization allowed for well

• -milling polymerization did not allow for controlling the molecular weight distribution, resulting in a broad polydispersity (Mw/Mn) of 2.01 (Table 4, entry 5). As mentioned, fast initiation over chain propagation is one of the requirements in a controlled polymerization. While TBD could chemically enhance

Synthesis of polydicyclopentadiene using the Cp₂TiCl₂/Et₂AlCl catalytic system and thin-layer oxidation of the polymer in air

• Zhargolma B. Bazarova,
• Ludmila S. Soroka,
• Alex A. Lyapkov,
• Мekhman S. Yusubov and
• Francis Verpoort

Beilstein J. Org. Chem. 2019, 15, 733–745, doi:10.3762/bjoc.15.69

• gradually happen during the exposure time of polydicyclopentadiene thin layers in the air as a result of the oxidation of double bonds. A new vibrational band at 1410 cm−1 in the IR spectrum appears which is originating from the primary radicals which are formed alongside the chain initiation. The kinetics

• chain process of PDCPD oxidation follows. Various mechanisms of chain initiation are possible, e.g., the formation of primary free radicals initiating the chain reaction of polymer oxidation (Equation 1). More often, the chain initiation step is described as a bimolecular interaction between oxygen and

• , and can be conveniently described as the reaction given in Scheme 5. Impurities remaining in the polymer after its purification can participate in the initiation of the chain oxidation. These impurities can include initiator or catalyst residues, metal impurities with mixed valences, in particular

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

• reactions of 7-oxanorbornene derivatives 13 and 14 were carried out with the so-called “ill-defined” catalysts, namely RuCl3·H2O and Ru(OTs)2(H2O)6 [27][28] (Scheme 3). However, these catalysts had limited usefulness due to a slow initiation rate and detrimental effect of water on the reaction mixture

Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands

• Tegene T. Tole,
• Johan H. L. Jordaan and
• Hermanus C. M. Vosloo

Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19

• for 80 °C, at 420 min. It also showed higher TOF at 60, 90 and 100 °C at 420 min. According to a DFT study by Getty et al. [19] the more positively charged the Ru, the slower the initiation rate of the catalyst. The calculated Mulliken atomic charge of Ru in 7 (0.934) is less positive than in 8 (0.976

• , precatalyst 6 showed a low initiation rate. This is also in agreement with the DFT study of Getty et al. [19], i.e., precatalyst 6 (0.988) has more positive Mulliken’s atomic charge on Ru than both 7 (0.934) and 8 (0.976). Its high activity at 110 °C with 69% selectivity is, however, remarkable for linear

• ruthenacycle. In addition, the relatively low ruthenium metal positive charge on 9 would cause it to have a high initiation rate constant [19]. On the other hand, the 3-Me group in 6 will strengthen the Ru–N chelation via inductive electron-donation and steric repulsion between the methyl group and the two

Ammonium-tagged ruthenium-based catalysts for olefin metathesis in aqueous media under ultrasound and microwave irradiation

• Łukasz Gułajski,
• Andrzej Tracz,
• Katarzyna Urbaniak,
• Stefan J. Czarnocki,
• Michał Bieniek and
• Tomasz K. Olszewski

Beilstein J. Org. Chem. 2019, 15, 160–166, doi:10.3762/bjoc.15.16

• initiation step. This unexpected catalytic activity might be due to the fact that catalysts 4b and 1a have different counter ions and therefore we decided to examine if there is an influence of counter ions on the catalytic activity. To achieve this we used analogues of 1a bearing different counter ions (1b

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• ) in the reacting solution. In order to enhance the ESI response of putative reactive intermediates, the reaction was performed with the charge-tagged tetrazine 4∙Br (R2, Scheme 5). A continuous-flow setup [4][17][18] was used for fast sampling of the reaction R2 directly after its initiation. A

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• and 4a clearly outperformed GII-SIMes, with catalyst 4a emerging as the most efficient of all (>97% conversion in 9 min). Complex 5a showed a higher initiation rate with respect to GII-SIMes, but eventually was found to be less efficient due to a decrease in its catalytic activity related to

• comparable to GII-SIMes and HGII-SIMes in the RCM of substrate 7 (Scheme 1), giving full conversion within 30 minutes, whereas the corresponding Hoveyda-type complexes 18b and 19b presented a more pronounced initiation period, giving good conversions in much longer reaction time (2–4 h) [16]. A similar trend

• was observed in the RCM of 9 (Scheme 2), but reaction rates were lower in all cases. As for 20a and 21a, the initiation rates in the RCM of 7 were observed to be faster than GII-SIMes, HGII-SIMes and 19a, while the initiation rates of 20b and 21b were lower than GII-SIMes and HGII-SIMes, but superior

Degenerative xanthate transfer to olefins under visible-light photocatalysis

• Atsushi Kaga,
• Xiangyang Wu,
• Joel Yi Jie Lim,
• Hirohito Hayashi,
• Yunpeng Lu,
• Edwin K. L. Yeow and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2018, 14, 3047–3058, doi:10.3762/bjoc.14.283

• = 12). On the basis of these observations, a proposed triplet sensitization mechanism is illustrated in Scheme 4. In this reaction, photocatalyst 8 serves as a catalyst of an initiation step through energy transfer from photoexcited 8* to xanthate 1 to form excited xanthate 1* and regeneration of 8 in

• ). Conclusion We have established a protocol for a photoinduced radical addition of xanthates to olefins using an iridium-based photocatalyst under blue LED irradiation, leading to diverse xanthate adducts. This reaction proceeds through a radical-chain propagation mechanism via an initiation involving a

Organometallic vs organic photoredox catalysts for photocuring reactions in the visible region

• Aude-Héloise Bonardi,
• Frédéric Dumur,
• Guillaume Noirbent,
• Jacques Lalevée and
• Didier Gigmes

Beilstein J. Org. Chem. 2018, 14, 3025–3046, doi:10.3762/bjoc.14.282

• generation of silylium cations is possible. These cations have been described in the literature for initiation of ring-opening polymerization processes [25]. Cations Ph-NVK+ produced in catalytic cycle (Figure 5B) have also been well noted in the literature as highly reactive structures [26][27]. Amines

• photopolymerization initiation as shown in [53] (see Part 3). For this purpose, the Ir complex was more interesting than the Ru one because of the longer excited state lifetime, lower oxidation potential leading to higher interaction rate constants with additives used for ring-opening photopolymerization (e.g

• polymerization reactions Polymerization reactions whose initiation is induced by photoredox catalysts has been detailed in part 1.4. Representative monomer conversions with different photoredox catalysts and upon different irradiation light for free radical polymerization and for cationic polymerization are

The activity of indenylidene derivatives in olefin metathesis catalysts

• Maria Voccia,
• Steven P. Nolan,
• Luigi Cavallo and
• Albert Poater

Beilstein J. Org. Chem. 2018, 14, 2956–2963, doi:10.3762/bjoc.14.275

• is ortho-substituted, there might be present steric repulsion with the NHCs, which might in turn facilitate the departure of the indenyl ligand [36]. Apart from reducing decomposition [37][38], this steric pressure should lead to faster rates for the initiation step of the metathesis reaction. This

• hypothesis will be examined computationally in order to assist catalyst design efforts. Results and Discussion We have studied the initiation cycle involving the transformation of the indenylidene precatalysts into the active methylidene for a series of olefin metathesis relevant complexes 1–6, using

• lengths are given in Å). Catalysts studied by DFT calculations. Precatalyst initiation in olefin metathesis (L = NHC ligand). Precatalyst initiation reaction pathway for catalysts 1–6 (M06/TZVPsdd//BP86/SVPsdd; Gibbs free energies in kcal/mol). Structural analysis for species I–III for catalysts 1–6 (in

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• different distances from the carbene carbon. We show that the predicted initiation rates of Grubbs, indenylidene, and Hoveyda–Grubbs-like complexes incorporating these carbenes show little variance and are similar to initiation rates of standard Grubbs, indenylidene, and Hoveyda–Grubbs catalysts. In all

• investigated cases the partial charge of the carbene carbon atom is similar, resulting in comparable Ccarbene–Ru bond strengths and Ru–P/O dissociation Gibbs free energies. Keywords: catalysts; cationic carbenes; DFT; initiation; metathesis; Introduction The isolation of the first stable N-heterocyclic

• , but also on the properties and initiation rates of the most important ruthenium-based metathesis catalysts, including Grubbs, indenylidene, and Hoveyda–Grubbs complexes, as well as carbene dimerization. We also considered two different solvents: dichloromethane, which is a standard solvent for

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• ether 7a in 92% yield. Two different paths can be invoked for metathesis of compound 7a. Metathesis initiation may occur by attack of the ruthenium alkylidene at the alkyne unit to produce the more substituted vinyl alkylidine intermediate 8a which may undergo concomitant ROM–RCM with the norbornene

• nucleus to provide the triene 9a (path 1). Alternatively the metathesis initiation may occur initially at the norbornene double bond to provide the ring-opened ruthenium alkylidine intermediate 10 (path 2). The latter then undergoes RCEYM to provide the tricycle 9a. With this background a solution of the

• acetylenic unit in 17 inhibits metathesis initiation at the acetylenic unit. The norbornene derivative 17 just remains inert under metathesis conditions. Thus metathesis in these examples proceeds through path 1 (Scheme 3). Conclusion In conclusion we have developed a protocol for the synthesis of condensed

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• initially monitored over time through gas chromatography, affording the conversion versus time diagram depicted in Figure 4. Figure 4 clearly shows that both tungsten complexes are active in the metathesis of 1-phenyl-1-propyne, with the bimetallic compound W2F3 (grey) showing a slower initiation rate

• compared to the alkylidyne complex WPhF3. For the bimetallic complex W2F3, an additional initiation step is required, in which the W≡W triple bond is cleaved and catalytically active alkylidyne species are formed. Therefore, the conversion of the substrate with catalyst W2F3 is significantly slower at the

Visible light-mediated difluoroalkylation of electron-deficient alkenes

• Vyacheslav I. Supranovich,
• Vitalij V. Levin,
• Marina I. Struchkova,
• Jinbo Hu and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2018, 14, 1637–1641, doi:10.3762/bjoc.14.139

• boron-centered radical anion 5. After the initiation event, the reaction proceeds via a chain mechanism. Thus, radical addition at the double bond gives radical 6, which abstracts a hydrogen atom from cyanoborohydride to generate boryl radical anion 5. The latter species can readily abstract the iodine

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• exploited for developing targeted cytotoxic agents: Dysregulation of translation initiation factors and regulators [14]. Mutations in epigenetic regulatory genes [15]. Overexpression of surface receptors like HER2R [16], folate receptor [17], GnRH receptor [18][19] and amino acid transporters [20

• the initiation of a clinical trial based on various PDCs consisted of two novel peptides selected after phage display that target murine A20 leukemic cells (ClinicalTrials.gov Identifier: NCT02828774). These clinical trials will focus on chronic lymphocytic leukemia (CLL). Except these two PDCs, there