A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• , such as 5 and 6, available via [3 + 2]-cycloadditions [21][22][23][24][25] or [3 + 3]-annulations [26] of trifluoroacetonitrile imines 7, respectively, were reported (Scheme 2). Noteworthy, the latter 1,3-dipoles are easily generated under mild conditions via base-mediated dehydrobromination of the

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• unsymmetrical 3,3'-diindolylmethanes (DIMs) with a quaternary carbon center has been developed via iodine-catalyzed coupling of trifluoromethyl(indolyl)phenylmethanols with indoles. In contrast to previously reported methods, the new procedure is characterized by chemoselectivity, mild conditions, high yields

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds

• Guanglong Pan,
• Qian Yang,
• Wentao Wang,
• Yurong Tang and
• Yunfei Cai

Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89

• radical initiator under mild conditions. A wide range of structurally diverse nitrogenous heterocyclic compounds including indolines, oxindoles, isoquinolinones, and isoquinolinediones have been accessed in high yields. This heterogeneous protocol features base- and transition metal-free, good catalyst

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• , which can provide the desired biguanides in one-step under relatively mild conditions. Given the moderate yields of the reported procedure, the reaction conditions should be reexamined in an exhaustive and systematic study. In addition, the development of new “biguanidilation” agents presenting other

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• -metal catalysts, such as in the Suzuki–Miyaura and Heck coupling reactions. Methodologies for forming different C–C bonds have recently been developed in the field of single-electron chemistry [63][64][65]. Considering that EDA-complex-initiated free-radical reactions are carried out under mild

• conditions, more attention has been paid to this efficient strategy for C–C-bond formation. In 2015, Yu and colleagues [27] proposed a method for direct C–H trifluoromethylation of aromatic hydrocarbons through an EDA complex. Trifluoromethylated product 61 was synthesized by employing tryptamine derivative

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• formation of an unexpected product, i.e., β-triazolylenone. Being inspired by the results, we intended to use 1,3-dicarbonyl compounds as detosylative alkylating agents that would lead to the formation of β-triazolylenones in a highly regioselective manner under mild conditions (Scheme 1d). Results and

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• kinetics, cost of metals, toxicity, difficulty in catalyst reusing and need of downstream processing. Significant efforts have thus been made to develop greener and sustainable catalytic systems featuring high efficiency under mild conditions. The use of sodium carbonate or bicarbonate as ecofriendly

Metal-free visible-light-enabled vicinal trifluoromethyl dithiolation of unactivated alkenes

• Xiaojuan Li,
• Qiang Zhang,
• Weigang Zhang,
• Jinzhu Ma,
• Yi Wang and
• Yi Pan

Beilstein J. Org. Chem. 2021, 17, 551–557, doi:10.3762/bjoc.17.49

• successfully studied. However, the disproportionate dithiolation of alkenes is unknown. Herein, a transition-metal-free protocol is presented for the vicinal trifluoromethylthio–thiolation of unactivated alkenes via a radical process under mild conditions with a broad substrate scope and excellent tolerance

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• respect, a bifunctional quinine-derived sulfonamide organocatalyst was developed to catalyze the asymmetric sulfa-Michael reaction of naphthalene-1-thiol with trans-chalcone derivatives. The target sulfa-Michael adducts were obtained with up to 96% ee under mild conditions and with a low (1 mol

• synthetic organic chemistry [22]. Thus, the SMA with thiols and α,β-unsaturated ketones are generally carried out at low temperatures and with high catalyst loading [23][24][25][26]. The studies that employ mild conditions and low catalyst loading use thiophenol derivatives or simple alkylthiols as

• sulfa-Michael additions of thiols to chalcones with sulfonamide-type organocatalysts in the literature [30][31], in this study, a new quinine sulfonamide organocatalyst derivative was developed to catalyze the enantioselective SMA of naphthalene-1-thiol to trans-chalcones under mild conditions and with

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• -dioxaphospholane-4,5-dicarboxylate (168) gave the corresponding phosphonodepsipeptides 169 in 65–86% yields under mild conditions. Although the diisopropyl ester was applied instead of diethyl ʟ-tartrate, a low diastereoselectivity (ratios varied from 55:45 to 67:33) was observed as well. Acetophenone (170

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• . A series of substituted products was obtained in SNAr reactions between 2,6-bistriazolylpurine derivatives and O- and C-nucleophiles under mild conditions. The products were isolated in yields up to 87%. The developed C–O and C–C bond forming reactions clearly show the ability of the 1,2,3-triazolyl

• 4a. Also hydrolysis of 2c into 4b proceeded under mild conditions and only gentle warming to 50 °C was required. 2,6-Bistriazolylpurine derivatives in SNAr reactions with C-nucleophiles Next, SNAr reactions between 2,6-bistriazolylpurine 2c and C-nucleophiles offered an easy way for the C–N bond

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• a packed column with K2CO3 is based on a simple set-up and issues due to channeling were not observed, the use of forcing conditions may not tolerate more sensible functionalities. As such, the phase-transfer-catalyzed process may be preferable in these cases due to its mild conditions which

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• was discussed previously [29]. The reaction of 4 with malononitrile-derived gem-dithiolate (5b, Scheme 1, route 2) also proceeded under mild conditions in DMF and bicyclic o-quinone 6b was obtained in a good yield. The brown crystals suitable for X-ray analysis were grown from an acetone/diethyl ether

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• biotransformation of gem-difluorocyclopropanecarboxamide (±)-83 (Scheme 34) occurred rapidly and under mild conditions to give (1R,3R)-amide 83 (46% yield, >99% ee) and (1S,3S)-acid 82 (51% yield, 87 % ee). Enantioselective hydrogenation of difluorocyclopropenes: Recently, Mikami and co-workers reported the

• . Further applications of free radical chemistry have developed through the use of radical initiators under comparatively mild conditions to form cyclopropylmethyl radicals, which can readily release their strain by opening to give homoallyl radicals. gem-Difluorocyclopropanes, because of their

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• obtain aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers. The products are structurally unique and represent highly functionalized compounds containing the gem-difluoroalkyl ether unit in addition to a bromochloromethyl group. The reaction proceeds under mild conditions and is compatible with variously

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• vinylphosphonates from simple and commercially available alkynes proceeds under mild conditions with high stereoselectivity, and thus enabling the rapid construction of molecular complexity. Results and Discussion We investigated the reaction of phenylacetylene (1a), Selectfluor®, and diethyl phosphite to afford β

• -fluorovinylphosphonates under mild conditions. First, we examined the catalytic activity of various transition metal catalysts, including Au, Ag, Cu, Rh, and Pd complexes (Supporting Information File 1). Among these metal salts, silver salts, especially AgOAc, were the most effective catalysts for generating the desired

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• yields but under very mild conditions with no need of any (photo)catalyst or additive, despite the scope of the process is in part limited since the presence of at least one electron-withdrawing group on an aromatic ring completely suppressed the reaction. Emission spectrum of compound 1e (red) and of

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• of aldimine and ketoimine substrates under mild conditions [18]. Early studies reported a positive effect of sonication on the classical aminocyanation procedures. The reaction rate of the classical Strecker reaction using cyanide salts, amines and aromatic carbonyl derivatives [19] or piperidone [20

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• were prepared by the reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (1) with the corresponding substrates, resulting in the selective alkylation of one of the nitrogen atoms of the imidazole ring. The reaction proceeds under mild conditions in a polar solvent, giving the alkylated

• corresponding to the CH(CF3)2 group were significantly broadened. While all attempts to involve guanine in the reaction with 1 failed (DMSO, 25–70 °C, 4 d), the reaction of adenine (5) or 2-fluoroadenine (6) with tetrakis(trifluoromethyl)-1,3-dithietane (1) was found to proceed under mild conditions (DMSO, 25

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• , only a slight decrease in the yield was observed (84%) along with the same stereochemical outcome. Also, the chiral sulfinyl auxiliary can be easily removed under acidic conditions to give the free amine. Treating 3i with HCl gas in methanol at 0 °C, the tert-butylsulfinyl group was cleaved under mild

• conditions and the target primary amine 4 was obtained with 57% yield. Conclusion In conclusion, we have explored arylethynes as new nucleophiles for the Mannich reactions of (R)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine. Quite unexpectedly, the diastereoselectivity of the reactions were noticeably

Activation of pentafluoropropane isomers at a nanoscopic aluminum chlorofluoride: hydrodefluorination versus dehydrofluorination

• Maëva-Charlotte Kervarec,
• Thomas Braun,
• Mike Ahrens and
• Erhard Kemnitz

Beilstein J. Org. Chem. 2020, 16, 2623–2635, doi:10.3762/bjoc.16.213

• such as hydrodefluorinations and dehydrofluorinations were observed, followed by hydroarylation and Friedel–Crafts-type reactions under mild conditions. Keywords: aluminum fluoride; C–F bond activation; dehydrofluorination; hydrodefluorination; hydrofluorocarbons; Introduction Hydrofluorocarbons

• for the synthesis of hydrofluoroolefins (HFOs), which have been regarded as the next generation of refrigerants, exhibiting zero ozone depletion potential (ODP) and a negligible GWP [11][12][13]. A considerable amount of studies has been carried out to synthesize HFOs under mild conditions [11][14][15

• activation of C–F bonds under mild conditions, and hence the addition of the silane HSiEt3 as a hydrogen source [27][48][49]. More recently, ACF was shown to efficiently convert the fluoroalkenes HFO-1234yf (1) and HFO-1234ze (4a) in the presence of the hydrogen source HSiEt3 into the hydrodefluorination or

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• FTIR and PXRD showed little to no structural change to the biomaterials after metal deposition. Heck coupling results demonstrate the importance of using ChNCs as opposed to ChsNCs in order to control the redox chemistry of Pd, with full product yield in relatively mild conditions using PdNP@ChNC. TEM

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• required for the coupling are not tolerated with the highly electrophilic ketimine moiety of 4-trifluoromethylpyrimidin-2(1H)-ones. The CEL reaction was successfully applied in the N-arylation of many heterocyclic systems [35][36][37] including non-fluorinated pyrimidin-2(1H)-ones [38][39] under mild

• conditions. There are a few thorough studies on this reaction with pyrimidine and purine nucleoside bases and their derivatives which are most closely related to fluorine-containing substrates 1 [40][41][42]. However, considering the high sensitivity and capricious nature of CEL reaction, we wish to report

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

• . One exciting development in C–F bond formation is the use of small-molecule photosensitizers, allowing the reactions i) to proceed under mild conditions, ii) to be user-friendly, iii) to be cost-effective and iv) to be more amenable to scalability than typical photoredox-catalyzed methods. In this

• for inducing different organic transformations under extremely mild conditions without threatening reagents and conditions [83][84][85]. There are three commonly observed and distinct mechanisms of photocatalytic activation [86] in the context of organic synthesis: i) Most reported photocatalytic

• -light irradiation by a household (19 W) compact fluorescent light (CFL) bulb (emitting variable wavelengths in the range of ≈365–625 nm) [195] and under mild conditions. Control reactions revealed that both the PS and light were essential for the reaction to occur. According to their report, benzylic C