A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• subsequent water elimination leading to a stable tertiary, bis-benzyl carbocation that evolves forming the corresponding alkene by proton elimination (Scheme 3). The reaction was carried out at 60 °C with 10 mol % of 16 (Table 2, entry 1), monitoring the formation of the products by 1H NMR and GC–MS (see

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• approach has been used to synthesise 1,2,3-triazole-linked sialic acid derivatives at C-2 from various non-aromatic alkynes, among which a long hydrophobic chain showed the best inhibitory activity (IC50 = 28 µM) for a bacterial neuraminidase [20]. More recently, a long alkyl chain (benzyl N-butylcarbamate

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

• , entry 1). Since the reaction seemed to stop after 30–40% conversion, it was speculated that the ester enolate chelate complex formation was incomplete due to consumption of the base. For instance, deprotonation of tyrosine residues in benzyl position has been observed previously in the derivatization of

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• ). The use of a sterically more demanding Fmoc-protecting group decreased the ee values even more for the minor diastereoisomer (Scheme 1, 3c). Surprisingly, with benzyl-protected oxindole, the reaction did not proceed (Scheme 1, 3d), which implies that the carbonyl group of the carbamate moiety in the N

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

• closely related analogues, one containing a bromo substituent and the other one incorporating an 8-membered instead of a 7-membered ring. The key transformation in this four-step synthesis, with an overall yield of 29%, is the Fischer indole reaction of 2-nitrophenylacetyl acetoacetate with 1-benzyl-1

• -phenylhydrazine in acetic acid that delivers methyl 2-(1-benzyl-3-(2-nitrophenyl)-1H-indol-2-yl)acetate in 55% yield. Keywords: anticancer; Fischer indole synthesis; Heck reaction; heterocyclic compounds; indolobenzazepines; latonduines; paullones; Introduction Indolobenzazepines are fused heterocyclic

• derivative 7 was generated in 79% yield by treatment of amine 6 with chloroacetyl chloride. Next, the aminoacetyl group in 7 was benzyl-protected to give 8 in 88% yield. Halogen exchange reaction using excess sodium iodide in acetone gave the desired iodo-alkyl derivative 9 in 79% yield. Lastly, our attempt

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• group present in 3′-O-benzyl-β-ᴅ-glucofuranosylpyrimidines [27]. In this article, regioselective acylation at the primary hydroxy group of 3′-azido-3′-deoxy-β-ᴅ-allofuranosylpyrimidines was carried out with the different biocatalyst Lipozyme TL IM using the same acylating agent, i.e., vinyl acetate but

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• product (Table 1, entry 5). However, tertiary amines with a benzyl group reacted very slowly and afforded the expected product in moderate yield (Table 1, entry 6). The reason for the incompatibility of tributylamine towards this method has yet to be explored. A synthesis of allylic cyanides via visible

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

• intermediate in each of the multiple PEG elongation cycles can significantly reduce the use of harmful organic solvents and other chemicals. In the literature, besides the DMTr group, other protecting groups including benzyl and silyl groups have also been used for PEG synthesis [15][19][21][24]. However, like

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• , ensuring the smooth progress of the total synthesis of hoshinoamide A. With the tripeptide 7 in hand, we went on to construct the peptide scaffold (Scheme 3). When tripeptide 7 was subjected to Pd-catalyzed hydrogenation conditions [16], the benzyl group was selectively cleaved to generate 8. Treatment of

• yield is shown in Table 1. Fmoc-Val-N-Me-ᴅ-Phe-Val-Pro-OH (8). Tripeptide 7 (2.3 g, 3.3 mmol) was dissolved in 30 mL of MeOH/HCOOH (v/v 9:1) and hydrogenized with Pd(OH)2 (500 mg) under H2 atmosphere for 10 hours to remove the benzyl groups. The reaction mixture was filtered through a pad of celite and

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• and the benzyl groups were removed by hydrogenolysis using 10% Pd(OH)2/C in methanol at ambient temperature with a H2 balloon, which afforded the target trisaccharide 1 in 68% yield over three steps (Scheme 6). The structure of 1 was confirmed by several NMR spectroscopic techniques such as 1H NMR

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

• to the styrene derivative selectively to afford a metastable benzyl radical [111] which is captured by BuOO• via a radical termination process. Iron-catalyzed oxidative addition/coupling and functionalization Carbofunctionalization Moving forward, the Fe-catalyzed carbofunctionalization of alkenes

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• as well as nickel- and palladium-derived complexes were optimized at B3LYP-GD3BJ/TZVP and B3LYP-GD3BJ/TZVP &SDD level of theory, respectively. The presence of the benzyl and 3-indolylmethyl groups is crucial in their efficiency as drugs. In order to have a complete overview of the systems, different

• with methanol. {Dimethyl (2RS,4SR,5RS)-1-(benzoylcarbamothioyl)-2-benzyl-5-(2,4-dichlorophenyl)pyrrolidine-2,4-dicarboxylate}2Ni (L1-Ni): Red solid, 113 mg, 92% yield; mp 321–323 °C (MeOH, decomp.); 1H NMR (400 MHz) δ 8.05 (d, J = 6.6 Hz, 4H), 7.92 (d, J = 8.2 Hz, 2H), 7.60–7.11 (m, 20H), 5.44 (d, J

• ), 1228 (78), 1229 (49); anal. calcd for C58H54Cl4N4NiO10S2: C, 56.5; H, 4.4; N, 4.5; S, 5.2; found: C, 56.9; H, 4.2; N, 4.6; S, 5.1. {Dimethyl (2RS,4SR,5RS)-1-(benzoylcarbamothioyl)-2-benzyl-5-(2,4-dimethoxyphenyl)pyrrolidine-2,4-dicarboxylate}2Ni (L2-Ni): Red solid, 109 mg, 90% yield; mp 305–307 °C

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

• 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

• potential targets for the versatile pyrazolo[1,2,3]triazine library presented herein. Conclusion In analogy to literature-known acid-induced conversions of triazene-benzyl acetamides to 3,4-dihydrobenzo[d][1,2,3]triazines, so far not described pyrazolo[3,4-d][1,2,3]-3H-triazines 5 were successfully

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• % (R)-CPA 2, the benzyl-substituted 3-alkenylindole 81 (dienophile) was subjected to a Povarov cycloaddition with the commonly used imine 80, giving the 2,3,4-tetrahydroquinoline as a single diastereomer in high yield and enantioselectivity and finely tolerating the high steric requirements necessary

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

• 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

• ), and identified 1-benzyl-1,2,3,4-tetrahydroisoquinolines bearing phenoxy and benzyloxy substituents (SG-005, SG-094; for structures of bioactive compounds mentioned in this text, see Figure S1 in Supporting Information File 1) on both aromatic rings as potent blockers with promising antitumor activity

• highly electrophilic N-acyliminium intermediates [17]. As a special aspect, we used a carbamate unit (instead of the commonly used carboxamide), ending up with 1-benzyl-1,2,3,4-tetrahydroisoquinolines bearing an N-ethoxycarbonyl residue, which in turn was easily converted directly into an N-methyl group

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

• . Both TBS and SEM protecting groups were tolerated, as demonstrated by the syntheses of the fluorenones 10u and 10v (52 and 46% yields). As expected, the O-benzyl group was not tolerated, giving only trace amounts of product 10w, as benzyl ethers are well known to undergo side reactions with free

• 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

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• derivatives. It was perceived that the MDO self-assembled in situ from amino acids and cinchona alkaloid derivatives. For example, on reacting (E)-2-[2-(3-aryl-3-oxoprop-1-en-1-yl)phenyl]acetaldehydes 21 with ethyl or benzyl (E)-2-[(4-methoxyphenyl)imino]acetates 22 in the presence of the MDO 23/24

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

• absence of organic halide, the copper salts catalyzed the hydroamination of the alkene [59]. Mechanistic studies showed that the copper–amido complex coordinated with alkenes, which then acted as a primary photocatalyst. After light irradiation, the excited alkene–copper–amido species offered a benzyl

• radical and the organocopper via SET with hydrogen atom abstraction from CH3CN. Subsequently, the benzyl radical was captured by the organocopper to generate the hydroamination products (Scheme 10). In 2020, the same group [60] reported the copper-catalyzed asymmetric dual carbofunctionalization of

• photophysical properties (Scheme 16). In 2019, Vlla’s group [76] explored the copper-catalyzed alkynylation of dihydroquinoxalin-2-ones 34 with terminal alkynes under irradiation. 4-Benzyl-3,4-dihydroquinoxalin-2(1H)-one 35 was subjected to an oxidation process with a CuII salt to generate a nitrogen radical

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

• tetrahydroisoquinoline derivatives, 7,12-dihydro-6,12-methanodibenzo[c,f]-azocine-5-carboxylic acids by three component Petasis reaction with the use of aminoacetaldehyde acetals bearing substituted benzyl groups as the amine components followed by Pomeranz–Fritsch double cyclization reaction. By applying this method

• , variously substituted 7,12-dihydro-6,12-methanodibenzo[c,f]azocine-5-carboxylic acids, via our modified method based on a combination of the Petasis reaction, in which we used aminoacetaldehyde acetals with substituted N-benzyl groups as the amine component and the Pomeranz–Fritsch double cyclization

• without alkoxy substituents, prepared from phenylboronic acid (5d), glyoxylic acid hydrate (4) and an N-benzyl aminoacetal 3d with good yield 79% (Scheme 4), it was necessary to perform the cyclization reaction using 70% HClO4 instead of 20% HCl. In these conditions, the desired product 7f was obtained

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• in 50% yield (Scheme 4b, 1.32 g). For synthetic utility, the directing group was conveniently removed by refluxing with KOH in EtOH and the benzyl-protected ester 5 was obtained in 75% yield. We also conducted several deuteration experiments to shed a preliminary insight into the mechanism. No H/D

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

• ) are shown in Figure 2. As can be seen, the BPNs displayed an excellent wide range of light absorption region up to 1000 nm. In this regard, BPNs are the only light absorbing component in the NIR region where CuII is completely transparent. Initially, the model reaction between benzyl azide (Az-1) and

• at 4.42 ppm and appearance of the new signal at 8.67 ppm corresponding to the triazole moiety confirmed successful click reaction under white LED exposure conditions after 4 h (Figure 3a). Kinetic studies conducted by 1H NMR analysis confirmed that the click reaction between benzyl azide and

• reaction to reform Cu(II). Similar observations were reported by the other photoinduced CuAAC reactions [41]. In order to demonstrate the functional group tolerance, the extent of the reaction was investigated on various alkyne groups using benzyl azide under both white LED and NIR light irradiation. The

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

• dropped significantly to 35% ee. Additionally, we tested the influence of substitution of the aromatic amine and prepared the benzyl-protected anthranilamide 1u. Unfortunately, the reaction between 1u and isovaleraldehyde (2a) did not deliver the corresponding product 3u even after a prolonged reaction

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• the desired stereochemistry inversion at the C5’ carbon. Treatment with excess NaH furnished a terminal epoxide derivative which after the sequential treatment with benzyl bromide and reduction with LiAlH4 afforded alcohol 102 (81% yield from 95). The free secondary alcohol was then protected as TBS

• ) via a Mitsunobu esterification. The resulting product 106 contained all the correct stereochemistry, which after removal of the benzyl protection, provided the target molecule brevipolide M (13) as a colorless oil. Sabitha’s strategy to brevipolide M and N (13, 14) Following the previous success

• treated with an acid to remove the isopropylidene protection and induce intramolecular cyclization to the 2’,5’-syn-furan 109 in 80% yield. This triol was subjected to excess sodium hydride and tosylating agent, and the mixture was allowed to react for 90 minutes, after which benzyl bromide was added to

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

• Matthew J. Fleming and
• David M. Hodgson

Beilstein J. Org. Chem. 2021, 17, 2385–2389, doi:10.3762/bjoc.17.155

• as only γ-amino ether 25 was observed in its absence. It was also important to carry out the reaction at −78 °C to avoid a 1,2-Wittig rearrangement of the lithiated benzyl ether [22]; this restricts the reaction to N-Bus-aziridines, as epoxides are not deprotonated by LTMP at such low temperatures

• hexane (69%, E/Z = 62:38) and the amount of dimer 24 curtailed (8%) by reducing the amount of LTMP from 2 to 1.2 equiv. The viability of a benzyl ether (Scheme 10) in the carbenoid eliminative cross-coupling offered a straightforward way to probe any effect of the size of the leaving group on

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• selectivity of α-stereochemistry was primarily due to the strong directing effect of the neighboring benzyl ether group with the Hg(OAc)2. When cyclic mercuric halide 8 was treated with NaBH4 and oxygen (O2) in DMF oxidative demercuration takes place to give alcohol 10 in quantitative yield (Scheme 4). The

• 1.4 equiv of Hg(OAc)2 and sodium bromide (NaBr) at room temperature, then β-ᴅ-arabinose derivative 18 was formed as the major product (Scheme 8) [45]. The high stereoselectivity of β-derivative 18 at the anomeric position was predominantly due to the presence of the benzyl groups at the C-2 and C-3

• -amino alcohol 38 leading to the formation of (1R,2R,6R)-9-benzyl-9-azabicyclo[4.2.1]nonan-2-ol (39). The bicyclic derivative 39 through the number of consequent reactions formed a highly potent (+)/(−)-pyrido[3,4-b]homotropane (40), a bridged nicotinoid (Scheme 15) [61]. Similarly, precursor 41 at room