Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• organocatalyst does not undergo oxidation or reduction but facilitates interaction between oxidant and substrate (Scheme 1, type II organocatalysis) are fluently discussed below to show the fundamental difference between type II and type III redox-organocatalysis. Organocatalysis by activation of redox

• addition to the electron-rich C=C bond [58] or proton loss followed by β-functionalization [59][60][61]. The iminium cation catalysis is used in the activation of electrophilic properties of enones for the nucleophilic epoxidation by hydroperoxides (Scheme 2B). N-Heterocyclic carbene (NHC) organocatalysis

• in oxidative processes for the activation of electrophilic properties of unsaturated substrates or for the activation of hydroperoxide oxidative properties. In Scheme 4A the proposed transition state for the Brønsted acid-catalyzed asymmetric Baeyer–Villiger reaction is shown, in which the

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• (non-targeted, e.g., modifying culturing conditions) and pathway-specific (e.g., heterologous expression or in situ pathway activation) approaches have been developed to awaken silent biosynthetic pathways [16]. Most importantly, however, genome mining can prevent the time-consuming re-discovery of

• minimally harbors three core domains, responsible for the activation and loading, tethering, and condensation of building blocks and intermediates. The biosynthesis is directional and starts at the N-terminal module with the activation and loading of the first building block onto the assembly line (Figure

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• catalyst but the reaction still requires thermal activation [21]. Thus, to our knowledge, the room temperature intramolecular azide–alkyne cycloaddition is unprecedented (plasmon-assisted click reaction at low temperature has been recently reported [22]). Excited by our initial finding, we tested various

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• one-pot reactions with recyclable organocatalysts [69]. Notably, we conferred K10 acid to promote the C–H activation in the synthesis of spirooxindolepyrrolidines, and used Zeolite HY catalyst to synthesize diastereoselective dispiro[oxindolepyrrolidine]s with a butterfly shape (Scheme 1A and 1B) [70

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• review paper exploring several procedures of C–H bond activation for the functionalization of N-oxides [12] and in 2019, Dongli Li and co-workers analyzed heterocyclic N-oxides with regard to their usefulness in synthesis of organic drug molecules and catalysis [13]. Many review papers have been

• proposed by the authors proceeded through cine-substitution. In the first step, the activation of imidazole 1-oxide 22 by oxalyl chloride led to the generation of imidazolium chloride 24, which transformed into intermediate 25 through nucleophilic substitution. Finally, the acidic hydrogen atom at C-2

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• , however, that the enantiomeric excess increases with an increase in bond length separation between the phosphorus and the R group. From the reaction evaluation we found that dual activation might be required from the catalyst in certain enantioselective reactions. Thus, CPA platforms that reintroduce a

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• characteristic of supramolecular catalysis is that the general modes of activation based on intermolecular interactions can operate on substrates in a selective way, and in confined environment, like the active site of natural enzymes [5][6][7][8][9][10][11][12][13][14]. As a result, molecular recognition of the

• distributions when performed inside the containers compared to the bulk solution. As mentioned above, activation of substrates, stabilization of intermediates and transition states through intermolecular interactions was established as one of the fundamental factors of supramolecular catalysis, and among these

• tetraaminobisthiourea chiral macrocycles as catalysts in decarboxylative Mannich reactions. Low macrocycle loading was used to catalyze the decarboxylative addition of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. It was reported that effective activation

Dissecting Mechanochemistry III

• Lars Borchardt and
• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1454–1456, doi:10.3762/bjoc.18.150

• activation to advance chemical synthesis on various fronts. Therefore, we hope you enjoy reading the variety of manuscripts in this Thematic Issues as much as we enjoyed editing it, which was only possible thanks to the impeccable assistance by the Editorial Team of the Beilstein-Institut. Lars Borchardt and

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• energies for selected (R)ISC processes of NI-PTZ-O and NI-PTZ and the activation barriers derived from these values clearly highlight the same trends obtained with the rate calculations [58]. For instance, a negligible RISC decay rate for the 3LE→1CT process in NI-PTZ-O roots on a large adiabatic energy

• difference and an even larger reorganization energy (0.75 and 1.92 eV, respectively), which lead to an activation barrier of ca. 3.42 eV (see details in Supporting Information File 1). Conversely, the sizable value of the RISC rate for the for the 3LE→1CT process in NI-PTZ roots on a small adiabatic energy

• difference and a similar value for the reorganization energy (0.23 vs 0.53 eV, respectively). This results in an activation barrier for the RISC process of ca. 0.076 eV, which is small enough to enable the RISC process at room temperature. In Scheme 2, a summary of the photodeactivation pathways for NI-PTZ

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• cage nitrogen atoms) and/or rotamers (restricted rotation around amide C–N bonds), which is well-known for amides and carbamates (Figure 4a). The activation barriers for the rotation across amide C–N bonds in 4a and 4c estimated by DFT (18.4 and 19.4 kcal/mol, respectively, ωB97XD/Def2TZVP, gas phase

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• in both techniques and probably pressure-induced activation and shearing deformation of reactant particles are more efficient using the grinding. We next examined the chelating effect of the above salens 1 with different transition metals. A library of metal–salen complexes was synthesized as

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• the intermediate C6–bromide to 11 was confirmed by 13C NMR, with C6 shifting downfield from δC 33.4 ppm to 51.6 ppm. Following this, dibenzyl phosphate was glycosylated with 11 using NIS/AgOTf activation of the thioglycoside, which proceeded in good yield (65%) to deliver 12. A final global

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• activation energy supported the proposed routes (see Supporting Information File 1 for details). Conclusion In summary, a borane-catalysed hydroboration of nitriles to give primary amines has been developed, transforming the previously stoichiometric reagent H3B·SMe2 into a catalyst. B-N/B–H transborylation

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• biomass-derived furfural and 5-methylfurfural, are converted into 3-silylated 2-furyl carbinols upon condensation with organomagnesium or organolithium reagents. The hydroxy unit of the carbinol adducts can be exploited to promote C3(sp2)–Si bond functionalization through intramolecular activation. Two

• approaches were contemplated for this purpose. Activation by alkoxides of the C3–SiEt3 or C3–SiMe2t-Bu bonds was ineffective. Conversely, treatment of the C3-benzyldimethylsilyl-appended derivatives with tetrabutylammonium fluoride led to cyclic siloxanes, which revealed to be competent donors for copper

• ][3]. As part of this effort, exploitation of furfural and corresponding derivatives attracts continuous attention [4][5][6][7]. In this area, we have actively investigated catalytic C–H activation reactions [8][9][10][11][12][13][14], and as part of this work, we have recently developed an iridium

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• , which have found, sometimes inadvertently, links between polymer and small molecule mechanochemistry that could eventually close the apparent gap between both branches. In turn, this might reveal synergistic opportunities to strengthen the field of mechanochemistry as a whole. Discussion Activation of

• mechanophores in polymers by ball milling Mechanochemical activation of mechanophores in polymeric materials is typically carried out by pulsed ultrasonication [5][6]. Under such conditions, the collapse of cavitation bubbles in the liquid medium creates a gradient that exerts mechanical force along the polymer

• ). Importantly, the BMPF mechanophore was also proven to be thermally stable up to 110 °C, which supports the conclusion that the mechanical force caused by the grinding was responsible for the activation of the BMPF mechanophores [28]. Comparative studies between ultrasound and ball milling have also

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• recently, two publications from the Werz group appeared concerning anodic activation of donor–acceptor cyclopropanes followed by their functionalization with arenes [43] or yielding oxy-ketones or 1,2-dioxanes [44]; the latter process was inspired by a previous report of Buriez [45]. The anodic

Electro-conversion of cumene into acetophenone using boron-doped diamond electrodes

• Mana Kitano,
• Tsuyoshi Saitoh,
• Shigeru Nishiyama,
• Yasuaki Einaga and
• Takashi Yamamoto

Beilstein J. Org. Chem. 2022, 18, 1154–1158, doi:10.3762/bjoc.18.119

• hydroperoxide/dicumyl peroxide/phenol from cumene, acetophenone from ethylbenzene, and others. Generally, molecular oxygen has been utilized in the straightforward oxidation of aromatic alkyls. However, since molecular oxygen is highly stable, activation of the molecular oxygen itself is necessary, which

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• with an activation energy of about 10.7 kcal·mol−1. On the other hand, if the removal of one H2O molecule occurs from the O–H and N–H groups, IS5 transforms into IS9 through TS14 with a high barrier of 31.8 kcal·mol−1. IS9 is then converted to product 10ab based on the shifting of H atom from the O–H

• bond to N atom (Scheme 4). This process is thermodynamically favorable by a Gibbs free energy (ΔG) of −6.5 kcal·mol−1. In addition, a second way from 4a, through the TS5 transition state, to form the IS3 intermediate requires an activation energy of ca. 33.7 kcal·mol−1. IS3 could release one H2O

• IS8 can be omitted because it is so fast with a small activation energy of 2.1 kcal·mol−1), the formation of product 10ab is superior as compared to its isomer. In terms of the value of the rate constant k, the direction of 10ab formation is in the range of 103–106 times faster than 10ab-v2. The

Synthesis of protected precursors of chitin oligosaccharides by electrochemical polyglycosylation of thioglycosides

• Md Azadur Rahman,
• Kana Kuroda,
• Hirofumi Endo,
• Norihiko Sasaki,
• Tomoaki Hamada,
• Hiraku Sakai and
• Toshiki Nokami

Beilstein J. Org. Chem. 2022, 18, 1133–1139, doi:10.3762/bjoc.18.117

• polyglycosylation via the electrochemical activation of thioglycosides is a practical approach for the preparation of chitin oligosaccharides. Hashimoto and co-workers have already reported the synthesis of protected precursors of chitin oligosaccharides by polyglycosylation of thioglycosides [5]. However, this is

• electrochemical activation occurs at the surface of the anode and the substrates must move to the surface of the electrode. To confirm the reactivity of oligosaccharides, we measured oxidation potentials of monosaccharide 1a, disaccharide 2a, and trisaccharide 3a using a rotating disk electrode (RDE) made of

• glassy carbon (Figure 8). The oxidation potential of oligosaccharides 2a and 3a (Eox = 1.76 and 1.74 V vs SCE) was higher than that of monosaccharide 1a (Eox = 1.70 V vs SCE). We also examined electrochemical activation of tetrasaccharide 4a to obtain octasaccharide 8a through the dimerization of 4a

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• ; spiro ring system; Introduction Single-electron transfer is one of the simplest modes for small molecule activation, employing a polarity inversion to generate radical ions which have proven to be unique reactive intermediates in the field of synthetic organic chemistry. A radical cation Diels–Alder

• reaction is a typical example of this activation mode since both the original diene and dienophile are electron-rich and thus not an effective combination of reactants [1][2][3][4][5][6][7][8][9][10][11]. Single-electron transfer makes the construction of six-membered ring systems possible. In general

Electroreductive coupling of 2-acylbenzoates with α,β-unsaturated carbonyl compounds: density functional theory study on product selectivity

• Naoki Kise and
• Toshihiko Sakurai

Beilstein J. Org. Chem. 2022, 18, 956–962, doi:10.3762/bjoc.18.95

• subsequent treatment with 1 M HCl. Electroreductive coupling of 1a–h with methyl vinyl ketone (2b) and subsequent treatment with 1 M HCl. Ep values of 1a–h derived from CV. Calculations of activation energies (∆G‡) and energy differences (∆G) from Dx to Ex. Calculations of ∆G from D’a to E’a. Supporting

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• and TS-4'-exo associate with nitrogen invertomers 4'-endo and 4'-exo of cycloadduct 4', respectively. Next, we determined the Gibbs energy of activation for nitrogen inversion in cycloadducts 4 and 4' to figure out if the invertomers undergo rapid interconversion. Having carried out full geometry

• , respectively. In turn, the Gibbs energies of activation corresponding to the endo approaches indicate that cycloadduct 4 (ΔG‡1+2j->4-endo = 19.3 kcal/mol) is more kinetically favorable than its epimer 4' (ΔG‡1+2j->4'-endo = 20.3 kcal/mol). The small free energy difference (1.0 kcal/mol) between the two

• activation for this cycloaddition reaction and to compare this value with the Gibbs free energy barrier calculated for the reaction between 1 and 2j (Scheme 9). The azomethine ylide 1 cycloaddition to the chloro-substituted cyclopropene 2m was also found to proceed by a one-step mechanism via two transition

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• was replaced by the Zn/Cu couple which was prepared without any metal activation by in situ ball milling of zinc and copper dusts. The advantage of the ball milling process is that the whole procedure is operationally very simplified. The reactive alkene generated was trapped in situ by several dienes

• , irradiation and electrochemistry as methods of chemical activation [8]. Based upon our experience in applications of this method to organic synthesis [9][10][11][12], we recognized its potential for the adjustment of conditions in zinc-mediated debromination reactions. Highly reactive dienophiles such as

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• catalytic amount of NaHSO4 was necessary. Since isocyanides are sensitive to acids, this approach was ruled out a priori. Aware of these issues, we were discouraged from employing p-tosylimidazole as well, since it requires acid activation to be effective as a dehydrating agent. Accordingly, we moved our

• entirely exerted in the solid phase through mechanochemical activation. In conclusion, we hope that our synthetic strategy could be considered a significant step toward a less impacting and more extensive research on isocyanide chemistry. Resonance forms of isocyanides. The purification process of a

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• , natural and (semi)synthetic endoperoxides with wide structural diversity show antimalarial activity against Plasmodium falciparum malaria. In this case, the reductive activation of the endoperoxide ring with the homolytic cleavage of the O–O bond leads to the generation of carbon-centered free radicals

• in the crystal structure, indicating that a tyrosyl radical abstracts the pro-S hydrogen atom from C13 of AA (Figure 2B and 2C) [48][52][53]. Mechanism of the cyclooxygenase reaction The enzyme reaction is initiated upon Tyr385 activation by the oxyferryl heme cation radical, which is generated