Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• NMR spectra. The solubility issues forced us to investigate also other modification protocols. Thus, macrocycle 11 was subjected to an ozonolysis with subsequent Wittig reaction in a one-pot manner (Scheme 4). Performing the ozonolysis in presence of pyridine led to immediate reduction of the primary

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• steps as shown in Scheme 3. First, reduction of commercially available indole-2-carboxylate with lithium aluminum hydride in dry tetrahydrofuran gave (1H-indole-2-yl)methanol (10) in 89% yield. The obtained alcohol was exposed to benzoyl chloride and triethylamine to furnish benzoate 11, which was

• previous observations [38]. Reduction of the nitro group by palladium-catalyzed hydrogenation in dry methanol gave 2a in 92% yield. Interestingly compound 2a undergoes ring-closure reaction spontaneously at room temperature to give trace amounts of 3a (59 mg, 2%) after column chromatography, when a 3.1 g

• , this method is not viable for N-benzylated indoles, where reduction in liquid ammonia with sodium is usually used as a standard protocol instead, even though successful reports are rare [41]. Other methods involve strongly basic and oxidative conditions [42], which are not tolerated by the CH2 group in

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• the reduction of the environmental effects of chemical synthesis [22]. The use of ultrasonic irradiation allows for optimal mixing of the reactants and the catalyst by enhancing the homogeneity of the reaction medium. It also decreases the chance of agglomeration of the heterogeneous nanoparticles

• , including amlodipine and nifedipine [24]. The structure of 1,4-DHP resembles the coenzyme NADH, which is very important in oxidation and reduction reactions in biological systems. 4-Substituted 1,4-DHPs have been used in the treatment of cardiovascular diseases as organic calcium channel modulators [25

• up to 97% using an external magnet. In a series of five reactions, the catalyst was used repeatedly without significant decrease in catalytic activity (Figure 7). The slight reduction of the yield in later reactions may have been a result of the loss of catalyst in the recycling process. Comparison

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• , a mixture of products is formed, among which 22 and 23 are the majority. It is important to note that the complexity of the reaction of β-NQS with primary aliphatic amines has already been reported in the literature. Fieser and Fieser [71] studied the reduction potentials of various naphthoquinones

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• group such as the phenethyl group for stepwise monodisperse PEG synthesis is the reduction of the PEG elongation cycle from three steps in two pots to two steps in one pot. Using the new approach, there is no need to isolate and purify the intermediate product after the deprotection step. Because

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• and co-workers demonstrated the generation of highly reductant CO2 radical anions through potassium formate hydrogen atom abstraction promoted by DABCO [25] (Figure 2c). This species was then used for reduction of (hetero)aryl and alkyl halides, and subsequent carboarylation of several styrenes

Effect of a twin-emitter design strategy on a previously reported thermally activated delayed fluorescence organic light-emitting diode

• Ettore Crovini,
• Zhen Zhang,
• Yu Kusakabe,
• Yongxia Ren,
• Yoshimasa Wada,
• Bilal A. Naqvi,
• Prakhar Sahay,
• Tomas Matulaitis,
• Stefan Diesing,
• Ifor D. W. Samuel,
• Wolfgang Brütting,
• Katsuaki Suzuki,
• Hironori Kaji,
• Stefan Bräse and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 2894–2905, doi:10.3762/bjoc.17.197

• a second oxidation wave that is more prominent and cathodically shifted for DICzTRZ at 1.05 V, compared to 1.14 V for ICzTRZ. No reduction wave is observed for DICzTRZ. The HOMO value calculated from the oxidation potential obtained from differential pulse voltammetry (DPV), is −5.21 eV, which is

• . DICzTRZ is less emissive than ICzTRZ (ΦPL of 72% [14]), with ΦPL in degassed toluene of 60% that decreases to 44% once exposed to oxygen. This reduction in ΦPL is in part due to the decrease in the radiative decay rate given the smaller calculated oscillator strength for the emissive S1 state for this

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• arylative spirocyclization reaction delivered product 40a in comparable yield, suggesting an initial in situ reduction of the Fe(III) precatalyst occurs in the early stages of the catalytic cycle. Although the mechanisms of Fe-catalyzed cross-coupling reactions are often complex [74][75] (Scheme 8), the

• operate in the absence of any external oxidants under an inert atmosphere. Although not investigated, Loh’s transformation most likely begins with the generation of an aryl radical from the reduction of the diaryliodonium salt with Fe(II) which subsequently abstracts a hydrogen from CH2Cl2 to generate an

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• hemicucurbituril-based macrocycle, alternately consisting of amidobenzene and 2-imidazolidione moieties was designed and synthesized. Based on the fragment coupling strategy, nitrobenzene-containing hemicucurbituril was firstly prepared facilely under alkaline environment, and reduction of the nitro groups

• reduction of 5-nitroisophthalic acid with NaBH4 and BF3·Et2O followed by subsequent bromination with PBr3 [46] and 2-imidazolidinone (6) were used as building blocks. By controlling the molar ratio of 5 and 6 at 1:10 or 6:1 and the reaction conditions, products 7 and 8 were readily accessible with 25.3

• imidazolidinone components were observed at rt. This indicated that the formed macrocycle is highly symmetric in solution. After successful construction of macrocycle 9, the aminobenzene-containing hemicucurbituril 4 was obtained by reduction of the nitro groups in 9 with Fe powder in H2O/EtOH at 86 °C for 2 h

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• final product 6 failed in the last step of the synthesis. The conversion of 12 to the reduced aminomethyl compounds 17 was challenging. While the reduction with LiAlH4 in THF gave good results (shown via TLC and LC–MS analysis), the isolated products were not stable and degraded quickly, making full

• found to be very low due to a reductive replacement of the fluoro atoms of the benzyl ring during the reduction of the nitrile with LiAlH4. Only a small amount (5% yield) of the desired compound was isolated. Also, a reductive replacement was observed during the conversion of 12h, yielding the

• intermediate 17a with R1 = Bn instead of R1 = bromobenzyl. Depending on the nature of the side chain R1 in compounds 12a–g, the reduction to compounds 17a–g leads to a change of R1 to a different side chain R1' which can be used for further transformation to R1'' by conversion with electrophiles. This was

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• , also as protective group for phenolic residues. After ring closure, the ethoxycarbonyl-protected phenols are deprotected simultaneously with the further processing of the carbamate group, either following route A (lithium alanate reduction) to give N-methylated phenolic products, or following route B

• approaches to the monomeric 1-benzyl-1,2,3,4-tetrahydroisoquinoline alkaloids are typically inspired by their biosynthesis and comprise Bischler–Napieralski-type cyclizations of arylacetamides (followed by reduction of the resulting 3,4-dihydroisoquinolines) or Pictet–Spengler-type cyclizations of

• by lithium alanate reduction [18][19]. In a novel total synthesis of the racemic alkaloid N-methylcoclaurine (1) performed in this course we also used the ethoxycarbonyl group successfully for protection of two phenolic groups at two different rings during the N-acyl-Pictet–Spengler reaction [15

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• remarkable reduction in deaths related to HIV/AIDS in the United States due to usage of combination drug therapies [26]. In these combination therapies, ʟ-(−)-2’,3’-dideoxy-3’-thiacytidine (1) is one of the standard components, having an enhanced pharmacological profile over AZT and other dideoxynucleotide

• % aqueous sulfuric acid, the isopropylidene group of 13 was selectively deprotected at 70 °C in dioxane to obtain diol 14. This diol was further cleaved using lead tetraacetate, and further reduction with sodium borohydride produced compound 15. The 5'-hydroxy group of 15 was then treated with tert

• ). Sodium periodate was used for oxidative cleavage of cis-diol 3d. The subsequent aldehyde was then converted to a vicinal diol by reduction with sodium borohydride. Further, it was protected by 2,2-dimethoxypropane to give the 1,3-oxathiolane derivative 21. The benzoylated compound 22 was obtained by

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• of biaryl aldehyde intermediates 8, reduction [60] in the case of nitriles 14, or Boc deprotection [61] for 14k, m, o according to standard protocols (Schemes 4–7; for details, see Supporting Information File 1). Although it may seem counterintuitive to first convert aldehydes 8 and nitriles 14 into

• Suzuki cross-coupling reactions, followed by reduction or reductive amination. The oxidative cyclization conditions are compatible with many functional groups on the aromatic rings (methoxy, chloro, cyano, nitro, and phenol protecting groups like TBS and SEM – but not benzyl and methylenedioxy

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• alkyne 27 with the assistance of CF3CH2O−. The added CuII precatalyst is likely reduced at the cathode to produce the requisite CuI. The base CF3CH2O− is produced through cathodic reduction of TFE. The addition of TFE to the reactions helps cathodic H2 evolution and may also stabilize the iminium ion

Solvent-free synthesis of enantioenriched β-silyl nitroalkanes under organocatalytic conditions

• Akhil K. Dubey and
• Raghunath Chowdhury

Beilstein J. Org. Chem. 2021, 17, 2642–2649, doi:10.3762/bjoc.17.177

• (Table 1, entry11). Upon further reduction in the loading of nitromethane (2) to 2.5 equivalents, the yield (82%), enantioselectivity (97% ee), and reaction time were not affected (Table 1, entry 12). Moreover, the reaction became sluggish when conducting the reaction with 2.5 mol % of the catalyst VII

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• , similar to the reaction performed in methanol (99:1 er, Table 1, entry 7). Using the same conditions as with catalyst (S,R)-C1, we also used 3 mol % (S,S)-C1 (Table 1, entry 8). The yield and diastereomeric and enantiomeric purity were very similar as with catalyst (S,R)-C1. However, a further reduction

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

• Tobias Klein,
• Franka V. Gruschwitz,
• Maren T. Kuchenbrod,
• Ivo Nischang,
• Stephanie Hoeppener and
• Johannes C. Brendel

Beilstein J. Org. Chem. 2021, 17, 2621–2628, doi:10.3762/bjoc.17.175

• smallest structures were obtained for BTU with Rg < 3 nm (Figure S12C, Supporting Information File 1). On the contrary, the reduction of the applied shear forces (500 rpm) limited the fragmentation rate for both samples. For BTU and after 10 min, a significant amount of the large structures (>40 min

• the rather harsh forces induced by this technique at the applied conditions. A reduction of the applied power might represent a suitable way to further limit the shear forces on the sample and gain more control, but this was not further tested. The peak maxima at around 80 min (BTU) and 65 min (BTP

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• reduction in conjugation. Another example of a tandem α-ketol rearrangement was used in the total synthesis of delitschiapyrone A (49), a cytotoxic natural product with previously demonstrated efficacy against several cancer cell lines. The final steps of the synthesis include a Diels–Alder reaction between

• eventually becomes isoleucine (Figure 14a). The enzyme catalyzes two consecutive reactions: an α-ketol rearrangement to generate a 3-hydroxy-2-ketoacid intermediate 61, followed by NADPH-dependent reduction to the dihydroxylated product 62 [18]. Interestingly, another reductoisomerase known as 1-deoxy-ᴅ

• 64 (Figure 14b) [20][21]. The other enzyme believed to catalyze an α-ketol rearrangement is AuaG, which is a monooxygenase that uses FAD and molecular oxygen to convert aurachin C (66) to 69 (Figure 14c) [22]. Subsequent reduction and dehydration by AuaH produces aurachin B (71). While the above are

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• accelerated freezing rate or reduction in cryogelation temperature will lead to smaller pore sizes throughout the cryogel. This is because the solvent freezes at a faster rate, allowing only a small amount of crystal growth [13][14]. Ivanov et al. researched the production of poly(acrylamide) (PAAm) cryogels

• hydrolysis [8]. It has also been found that degradation of chitosan/dextran cryogels resulted in an average increase in pore size, possibly due to thinning of the pore walls and reduction in crosslinks [32]. In general, mechanical property analysis of degraded cryogels is a topic largely overlooked by

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• ruthenium-based catalysts and copper-based catalysts are discussed, and the strong reduction ability of copper complexes is explained. Subsequently, mechanisms of the photoredox catalysis by CuI and CuII are summarized, and the copper-catalyzed reactions, including alkene functionalization, alkyne

• electrons from donors are relatively scarce in the literature. Thus, the RQC pathway rarely occurs for CuI-photocatalyzed reactions. Yet, CuI complexes have the potential to replace ruthenium or iridium-based photocatalysts in reductive photoredox reactions due to their strong reduction ability [22][29

• product Nu–R can be obtained through an inner-sphere pathway between [LnCuIINu]X and the radical R• [41][42] (Scheme 5A). Alternatively, a photosensitizer generated a radical via reduction or oxidation, and is not engaged in the key bond construction. [LCuI] is photoexcited to generate LnCuI*, which

Synthesis of new substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids containing a tetracyclic tetrahydroisoquinoline core structure

• Agnieszka Grajewska,
• Maria Chrzanowska and
• Wiktoria Adamska

Beilstein J. Org. Chem. 2021, 17, 2511–2519, doi:10.3762/bjoc.17.168

• ) carried out in refluxing toluene using a Dean–Stark apparatus followed by the reduction with NaBH4 (not shown). When the condensation of acetal 1 and aldehyde 2f and the subsequent reduction were carried out in EtOH at rt, according to our procedure applied for the synthesis of aminoacetals 3a–e, the

In-depth characterization of self-healing polymers based on π–π interactions

• Josefine Meurer,
• Julian Hniopek,
• Johannes Ahner,
• Michael Schmitt,
• Jürgen Popp,
• Stefan Zechel,
• Kalina Peneva and
• Martin D. Hager

Beilstein J. Org. Chem. 2021, 17, 2496–2504, doi:10.3762/bjoc.17.166

• . 23 µm). However, the width and the length of the scratch is nearly unchanged. Thus, the overall healing efficiency is lower compared to the reduction of the scratch depth. In contrast, the analysis of the healing behavior of P2 was just impossible. The scratching of the material resulted in no

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• . In this work, we report a new synthetic strategy to the photochemical reduction of CuII to CuI for the CuAAC reaction using BPNs as the photo-initiator under NIR light. Results and Discussion The detailed preparation and characterization of the initial BP crystals and BPNs were previously reported

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• cyclic voltammetry (CV) in dry acetonitrile. The obtained voltammogram, recorded at a scanning rate of 50 mV/s, is given in Figure 11. The HOMO and LUMO energy levels were deduced from the onset potentials of the oxidation and reduction waves, respectively. The potential of the saturated Ag/AgCl

• /Fc+ with respect to zero vacuum level. The onset potentials for the oxidation and reduction of 3c were 1.50 eV and −1.36 eV, respectively. Thus, their LUMO and the HOMO energies were found to be −2.92 eV and −5.78 eV, respectively, giving rise to an electrochemical band gap of 2.86 eV. We noticed a

Enantioselective PCCP Brønsted acid-catalyzed aminalization of aldehydes

• Martin Kamlar,
• Robert Reiberger,
• Martin Nigríni,
• Ivana Císařová and
• Jan Veselý

Beilstein J. Org. Chem. 2021, 17, 2433–2440, doi:10.3762/bjoc.17.160

• diuretic drug fenquizone used for the treatment of hypertension [7][8], or evodiamine, a stimulant used in fat reduction or inflammation [9][10][11]. Moreover, it was reported that both enantiomers of 2,3-dihydroquinazolinones exhibit different bioactivities [12][13]. Thus, the development of