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

• ) immobilized on polyacrylate (Lewatit), commonly known as Novozyme® 435 and Thermomyces lanuginosus lipase immobilized on silica, commonly known as Lipozyme® TL IM in different organic solvents, such as THF, acetonitrile, toluene, acetone, DIPE and 2-Me-THF. Vinyl acetate was used as acetyl donor at

• treated in 2-Me-THF with Lipozyme® TL IM (10 wt % of the substrate nucleoside) and vinyl acetate at 40 °C and 200 rpm in an incubator shaker to afford the monoacetylated nucleosides 15a,b in quantitative yields in 2 h (Scheme 3). The monoacetylated nucleosides 15a,b were mesylated using mesyl chloride in

• 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

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

• )phenyl]ethylene in acetic acid efficiently produced 4-vinyl-1,2-naphthoquinones 55 and 4-aryl-1,2-naphthoquinones 56a,b, respectively, under nickel(II) catalysis, forming a C–C bond (Scheme 16) [103]. When the reaction was carried out in 10% aqueous methanol solution at room temperature for 5 hours, 56b

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

• reaction, while the product of β-elimination of the tosylate – a vinyl ether – is inert under the reaction conditions. Compounds 3a–l were subjected to the study. All the compounds except 3h were found to be stable under the coupling conditions while product 5 was formed as indicated by TLC analysis

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

• first Fe-catalyzed cross-coupling reaction between Grignard reagents and vinyl halides [37]. As of late, the development of Fe-catalyzed cross-coupling methodology and mechanistic rationales have burgeoned [38]. Today, the rate of growth within the field of iron catalysis is much greater than that

• of the alkyl radical generating the cross-coupled product cannot be ruled out [57][60]. In 2020, Gutierrez and co-workers developed a Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes 14 with alkyl bromides 13 and aryl Grignard reagents 2 (Scheme 4) [61]. Using

• utility of their reaction, the authors studied the one-pot conversion of the vinyl azides to 2H-azirines 161. The carboazidation reaction for the aryl alkynes was completed in a comparable amount of time. A myriad of different functionalized π-systems was tolerated by the reaction, demonstrating its

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

• Chuanhua Qu,
• Run Huang,
• Yong Li,
• Tong Liu,
• Yuan Chen and
• Guiting Song

Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193

• arylalkenes or alkynes provided an attractive option for the synthesis of vinyl sulfones [19][20][21][22][23] (Scheme 1B). However, in contrast to the reaction of TosMIC as tosyl source with various aryl olefins, reports relating to reactions of TosMIC with electron-deficient olefins such as p-QMs for the

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• -stereoselective epoxidation of 2,3-dihydroisoxazole with in situ-generated DMDO, the syn-selective α-chelation-controlled addition of vinyl-MgBr/CeCl3 to the isoxazolidine-4,5-diol intermediate, and the substrate-directed epoxidation of the terminal double bond of the corresponding γ-amino-α,β-diol with aqueous

• rt, 16 h, 68%; (c) oxone, NaHCO3, acetone/H2O 3:2, 0 °C to rt, 80 min, 99%; (d) HCl (37 wt % in H2O), acetone/H2O 4:1, 0 °C, 30 min, 93%. Synthesis of final pyrrolidines (±)-1 and (±)-2. Reagents and conditions: (a) vinyl-MgBr, CeCl3, THF, 0 °C to rt, 16 h, 73%; (b) Zn dust, AcOH, 40 °C, 24 h, 85

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

• the oxathiolane precursor 56a from acyclic precursors. The method used chloroacetic acid (53), vinyl acetate, sodium thiosulfate, and water to construct the oxathiolane moiety. The use of sulfenyl chloride provided a new method to access such oxathiolanes (Scheme 16). Thioglycolic acid (3o), upon

• reaction with ʟ-menthol, afforded the relevant thiol-substituted esters 54, which further reacted with sulfuryl chloride to give compound 55. The reaction of compound 55 with vinyl acetate constructed a sulfur–carbon bond and produced 3k. The sulfuryl chloride reagent simultaneously allowed for

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• NOESY correlations between the vinyl proton and the aromatic protons or methyl groups in neighboring aryl substituents (see Supporting Information File 1). However, the configuration of nitrile 2o was unclear. Benzene, o-, m-, p-xylenes, and 1,2,4-trimethylbenzene (mesitylene) were included in the

Ligand-dependent stereoselective Suzuki–Miyaura cross-coupling reactions of β-enamido triflates

• Tomáš Chvojka,
• Athanasios Markos,
• Svatava Voltrová,
• Radek Pohl and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 2657–2662, doi:10.3762/bjoc.17.179

• -diaryl-substituted enamides is observed. Thus, the method provides synthetic access to both isomers of the target enamides from (Z)-β-enamido triflates. Keywords: enamides; isomerization; Suzuki–Miyaura coupling; vinyl triflates; Introduction Enamides are substrates of high value in organic synthesis

• of cytotoxic, antifungal, or antibiotic properties [10][11][12]. Modern stereoselective syntheses leading to highly substituted enamides include cross-coupling of vinyl (pseudo)halides or organoboron compounds [13], hydroamidation of alkynes [14][15][16], ynamide functionalization [17][18][19], or

• bond of vinyl (pseudo)halides during the Suzuki coupling have been published [25][26][27][28][29]. Typically, inversion of configuration occurs on substrates containing a double bond in conjugation with an electron-withdrawing group, such as the carbonyl group in enones [27][30]. We hypothesized that

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

• acids have been shown to catalyze the reactions via single or double hydrogen bonding [57][58]. Saito et al. accomplished the chiral phosphoric acid-catalyzed intramolecular aza-Michael addition reaction of N-unprotected 2-aminophenyl vinyl ketones 90 to obtain chiral 2-substituted 2,3-dihydro-4

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

• found with Pd(OAc)2/bpy as the catalyst, N-methylacetamide as the solvent, and a temperature of 80 °C. Variously substituted indoles as well as esters of 118 (R = aryl, alkyl, vinyl) were generally well tolerated, but oxa- (X = O) and azo- (X = NR) cyclobutanes met with limited success. Alternative

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

• . Common cryogel compositions include natural polymers such as gelatin and chitosan, and synthetic acrylamide-based polymers and poly(vinyl alcohol) (PVA) [12][13][14]. The reader is directed to a recent review by Thakor and co-workers which discusses cryogel synthesis in greater depth [15]. 2. Cryogel

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• geometry was inferred from its NOESY spectrum, which showed a weak but distinct correlation between the vinyl proton singlet (δ 5.66) and the methylene group flanked by nitrogen and the ester (δ 4.06). The E-geometry was also suggested by the chemical shift of the hydrogen atoms at C-3 of the pyrrolidine

• the nucleophile to the carbonyl site, while in the latter case insertion of the vinyl unit between the carbonyl and the aryl ring makes the electrophilic site in the enaminone significantly less crowded. Cyclization of enaminones bearing heteroaromatic substituents proceeded very well (Table 2

• interaction between the vinyl hydrogen (δ 5.55) and the methylene unit adjacent to the ester (δ 3.96). The through-space anisotropic deshielding of C-3 in the ring (δ 3.32) by the carbonyl group also supported the assignment of the geometry. Microwave heating of intermediate 25a with silica gel in xylene

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

• [Cu(dap)2Cl] and visible light are necessary for this transformation. In 2013, Ollivier and co-workers [45] successfully applied the same strategy to the allylation of diphenyliodonium 2. In 2017, Liu’s group [46] reported the copper salt-catalyzed cyclization of vinyl azides 3 with ammonium

• resulting cyanoalkyl radical then adds to the alkene to form a new alkyl radical. This radical is captured by a high-valent CuIII complex, which undergoes a reductive elimination to give the target product (Scheme 12). In 2018, Reiser and co-worker [63] established a CuII-catalyzed oxo-azidation of vinyl

• with oxime esters. Oxo-azidation of vinyl arenes. Azidation/difunctionalization of vinyl arenes. Photoinitiated copper-catalyzed Sonogashira reaction. Alkyne functionalization reactions. Alkynylation of dihydroquinoxalin-2-ones with terminal alkynes. Decarboxylative alkynylation of redox-active esters

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• -annulation reaction may undergo a free-radical addition pathway. Firstly, NFSI oxidizes Cu(I) to form bissulfonylamidyl radical 10. Secondly, intermolecular nitrogen free-radical addition to the alkyne provides the vinyl radical 11. Then, there may be two possible pathways. Path a: vinyl radical 11 is

• trapped by Cu(II) to deliver the Cu(III) species 12, which undergoes intramolecular annulation and reductive elimination to afford the desired product 8 and regenerate the Cu(I) catalyst. Path b: vinyl radical intermediate 11 is oxidized by Cu(II) to give the cationic vinyl species 14. Finally, the

• ]. Then, they also reported another CuH-catalyzed coupling reaction of 1,3-enynes 54 and nitrile to prepare polysubstituted pyrroles 55 (Scheme 21) [66]. The substrates 54 could be easily prepared by Sonogashira coupling of terminal alkynes and vinyl halides. It is worth mentioning that the addition of

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• attractive strategy for the synthesis of carbazole derivatives [28][29][30][31][32][33][34][35][36][37][38][39][40]. In recent years, by using the one-pot domino synthetic strategy of in situ-generated 2-vinyl- or 3-vinylindolines and sequential Diels–Alder reaction with activated dienophiles, we have

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• bond of these oxadiazoles quantitatively resulted in E/Z-vinyl triflates. The reactions of the cationic intermediates have been studied by DFT calculations and the reaction mechanisms are discussed. Keywords: acetylene-oxadiazoles; Friedel–Crafts reaction; hydroarylation; superelectrophilic activation

• protonation of 5-acetylenyl-1,2,4-oxadiazoles 3 (Table 1), one would propose the following reaction pathways for compounds 3 in Brønsted superacids (Scheme 2). Protonation of oxadiazole 3 affords dication B, which may react with counter anion of acid X− giving rise to vinyl derivatives 4. In the presence of

• vinyl triflates 4a–c with a predominant formation of Z-isomers as product of an anti-addition of TfOH to the acetylene bond (Scheme 3). E/Z-Stereochemistry of compounds 4a–c was determined by H,F-NOESY correlation between vinyl proton (>C=CH–) and the CF3 group from the TfO substituent (see Supporting

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

• epoxide using vinyl Grignard reagent followed by esterification with acrylic acid (35) proved to be inefficient due to low reproducibility and poor isolation of product 36. The strategy was altered by changing the terminal epoxide 34 to an allylic alcohol (95%) utilizing dimethyl sulfonium methylide

• -promoted double bond migration. The cyclopropyl functionality in 46 can be assembled from the reaction of sulfur ylide and the α,β-unsaturated ketone 47, which in turn can be realized from the cross metathesis between commercially available ethyl vinyl ketone (48) and the C2-symmetrical diene-diol 49. The

• afforded in 78% yield as an (E)-isomer exclusively after reaction with excess ethyl vinyl ketone (48) in the presence of a catalytic amount of Grubbs II catalyst and CuI. The free secondary alcohol in 51 required a protection prior to the next transformation. For this purpose, MEMCl was chosen instead of

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• this protocol using the chiral iPrBiOx ligand under slightly modified reaction conditions (Scheme 19) [72]. Recently, Chu achieved the selective assembly of vinyl and aryl functionalities onto saturated cyclic hydrocarbons via a photoredox nickel-catalyzed sequential C–O decarboxylative vinylation

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• method using π-activated alcohols has frequently been used for xanthene synthesis. Some of these methods are the stereoselective synthesis of 9-vinyl-substituted unsymmetrical xanthenes and thioxanthenes by intramolecular FCA reaction [39], Lewis acid-catalyzed intramolecular FCA [40], and the synthesis

• synthesis is based on the o-quinone methide intermediate [54][55][56][57][58]. The carbocation formed by the activation of an alkene with acid turns into an intermediate o-quinone methide, resulting in a successful cyclization. As seen in the mechanism, the acid catalyst adds to the vinyl group, allowing

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

Towards new NIR dyes for free radical photopolymerization processes

• Haifaa Mokbel,
• Guillaume Noirbent,
• Didier Gigmes,
• Frédéric Dumur and
• Jacques Lalevée

Beilstein J. Org. Chem. 2021, 17, 2067–2076, doi:10.3762/bjoc.17.133

• )vinyl)-3-cyano-5,5-dimethylfuran-2(5H)-ylidene)malononitrile in 65% yield. A second Claisen–Schmidt condensation of 2-(4-((E)-2-((E)-2-chloro-3-(ethoxymethylene)cyclohex-1-en-1-yl)vinyl)-3-cyano-5,5-dimethylfuran-2(5H)-ylidene)malononitrile with the appropriate 3-alkyl-1,1,2-trimethyl-1H-benzo[e]indol-3

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• (transformation of the vinyl group at C-6 was preferred, except for the reactions of isoxazoline (±)-4 with 7f and 7g), while all CM reactions of (±)-6 were completely regioselective (the vinyl group at C-6 was transformed first). This can be explained by steric hindrance: the substituent at C-3 on the

• isoxazoline ring shields the vinyl group at C-4 from reacting with the bulky catalyst molecules (Figure 4). For the smaller Me or Et groups, this effect is relatively weak (only some reactions of (±)-5 with 7c and 7e were completely regioselective). The large Ph group, however, provided complete

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• -handle, their fluorinating power was low. They could fluorinate only reactive carbanions, but not aromatics, olefins, vinyl acetates, trimethylsilyl or alkyl enol ethers, and so on. Soon after (1986), Schwartz and co-worker reported the stereospecific synthesis of alkenyl fluorides with N-fluoro-N-tert

• shows 31 examples and their methods of preparation. Umemoto and co-worker also reported the synthesis of a polymer version, poly(vinyl-N-fluoropyridinium salts) of these reagents [36]. The reactivities of many N-fluoropyridinium salts were examined [32] and mainly five kinds of N-fluoropyridinium salts

• , olefins, silyl enol ethers, vinyl acetates, sulfides and so on, under mild conditions with high selectivity and yields [29][30][31][32]. All these reactions could be carried out routinely using standard glassware in normal laboratory environments and without any specialist training. Some interesting

Electron-rich triarylphosphines as nucleophilic catalysts for oxa-Michael reactions

• Susanne M. Fischer,
• Simon Renner,
• A. Daniel Boese and
• Christian Slugovc

Beilstein J. Org. Chem. 2021, 17, 1689–1697, doi:10.3762/bjoc.17.117

• , the difunctional divinyl sulfone was tested as the strongest Michael acceptor (E = −18.36, for phenyl vinyl sulfone [19]) under investigation. In distinction from the experiments described above, three equivalents of the alcohol were used. In general, the different catalysts perform very similar in