Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• thioglycosides prepared from deoxyfluorinated 1,6-anhydro-2-azido-β-ᴅ-hexopyranose precursors by ring-opening reaction with phenyl trimethylsilyl sulfide. Nucleophilic deoxyfluorination at C4 and C6 by reaction with DAST, thioglycoside hydrolysis and azide/acetamide transformation completed the synthesis

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• enantioselectivities were low to moderate (up to 60% ee; Table 34) [14]. Another option to obtain the linear product is the ring opening of the addition product of the arylboronic acid to the dihydropyran-2-one derivative (Scheme 23) [14]. The Minnaard group next focused on the increase of the reactivity of ortho

• arylboronic acids [59]. Attempt to use the catalytic system L2/Pd(TFA)2 for the addition of phenylboronic acid to 3-methyl-2-cyclohexenone [14]. Ring opening of an enantioenriched tetrahydropyran-2-one derivative as alternative strategy to linear products [14]. Synthesis of biologically active compounds from

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

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• gave the desired THP as a 14:1 mixture of trans- and cis-265 in 80% yield. The trans-265 was obtained as a major isomer, where the reaction proceeded through the 6-membered chair-like transition state 264, and the electrophilic ring opening of cyclopropane by the oxocarbenium ion was believed to

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• product is then reacted with unprotected thymine which, in the presence of stoichiometric amounts of sodium hydride, results in the epoxide ring opening and the formation of the glycol backbone. The pre-amidite is then phosphitylated yielding the desired GNA-T amidite (Scheme 3). Recently, this simple

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• electron-rich pyrazolylamine led to the formation of intermediate A. Simultaneously, intermediate B (condensation of arylgyoxal and primary amine 32b undergoes C=N addition with intermediate A. Intramolecular cyclization of C yields a macrocyclic intermediate D which is followed by p-TsOH-promoted ring

• opening resulting in imine intermediate E. A consecutive intramolecular cyclization and tautomerization yields azepino[5,4,3-cd]indoles 143b. 9 Quinolines Quinolines are bicyclic aromatic heterocycles consisting of a fused pyridine and benzene ring. Quinoline and its derivatives are important both from

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• following the same procedure as described above for the EtOH treatment. To our surprise, the decomposition was much slower as expected (TLC monitoring, see Supporting Information File 1). It was assumed that the ring-opening could be influenced by water or by the in situ-generated thiophosphonic acid. Thus

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• ] (79% yield) as the sole product (Scheme 3). Ring opening of trans-epoxide 13 by HBr(g)–MeOH gave bromotriol 14, which is an ideal substrate for the synthesis of the aminocyclooctanetriol 18. For structural proof, bromotriol 14 was converted into the corresponding acetate 15 using Ac2O in pyridine and

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• thermal radical cyclization reactions according to the persistent radical effect [79][80] forming functionalized cyclopentanes 6 (Scheme 1B). Based on this sequence various other reaction pathways can be envisaged. Among them we hypothesized that the nucleophilic ring opening of simple epoxides 7 by N

• cyclizations to lactams of type 10 based on the persistent radical effect (PRE) are unknown and may provide a simple access to 3,4-disubstituted γ-lactams. We report here that tandem nucleophilic epoxide ring-opening/Brook rearrangement/radical oxygenation reactions are indeed very effective for the synthesis

• Information File 1 for details). The (R)-configuration at C2 as well as the (S)-configuration at both, C4 and the N-arylethyl group were established (Figure 2). A good diastereoselectivity was also observed for the ring-opening/Brook rearrangement/oxygenation sequence with cyclohexene oxide 7f, which

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

• cosmetics [147]. The catalyst could be recycled, however, with reduced performance due to Pt nanoparticle oxidation. 3.1.2 Polybutadiene (PBD): Partial depolymerisation of 1,4-PBD (cis, trans, Mw 1800–500000 g⋅mol−1) was achieved by an unconventional tandem ring-opening–ring-closing metathesis route

• bioderived plastic [252] that is manufactured on a 190 kton scale directly from lactic acid by condensation or from lactide by ring-opening polymerisation (Scheme 8) [253][254]. The main renewable raw material for lactic acid is starch, e.g., from corn, cassava, sugarcane or beet pulp [255]. Owing to the

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• challenging [15][16], and this was also the case for (rac)-13, since we first obtained the incomplete triene intermediate (rac)-15 as a result of only ring-opening metathesis (ROM) mediated by the Fischer carbene complex [Ru]=CH–OAc [6], generated by the reaction of Zhan catalyst-1B (14) with vinyl acetate

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• , conveniently prepared by [3 + 2] cycloadditions of terminal alkynes with sulfonyl azides, have been used as the precursors to N-sulfonylindoles by transition-metal-catalyzed transannulation reactions. In the presence of Rh(II) or Ni(0) catalysts the triazole ring-opening takes place and intermediate highly

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• , followed by a favoured 6-endo-trig cyclisation driven by the 4-methoxy group to form the 6,6-spirocycle 11. The addition of water and subsequent ring-opening would then form the acid 12, which upon elimination of water would then provide the observed acid chloride 13. We wished to also determine whether

Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity

• Dmitrii A. Shabalin,
• Evgeniya E. Ivanova,
• Igor A. Ushakov,
• Elena Yu. Schmidt and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29

• ring opening with formation of the linear intermediate C. In comparison with alkyl-, aryl-, and hetarylhydrazines [11] as well as semicarbazide and its derivatives [12], the nucleophilicity of the internal nitrogen atom of hydrazide 2 is significantly reduced. As a result, the interception of the

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

• . It will examine the role of the fluorine substituents in both ring-forming and ring-opening reactions, as well as methods for obtaining difluorocyclopropanes as single enantiomers. Several examples are provided to highlight the biological importance of this class of compounds. Keywords: biological

• -difluorocyclopropanes. First, we discuss the synthetic routes to gem-fluorocyclopropane derivatives. Then, we review the chemical transformations, emphasizing ring-opening reactions. Finally, we survey the biological activity of significant molecules that possess the 1,1-difluorocyclopropane fragment in the structure

• ]. The radical ring-opening polymerization (RROP) provides a synthetic route to fluoropolymers, which are useful materials [91]. The RROP of gem-difluorovinylcyclopropane (90) gave mainly the polymer with an unsymmetrical repeating unit, by the cleavage of the C2–C3 bond in the ring (Scheme 44, path a

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• -azabenzotriazole ring to the 7-azabenzotriazoline ring 18 and cleavage of the N–O bond through delocalization of the lone pair at N-2 to liberate 1 and 1H-[1,2,3]triazolo[4,5-b]pyridine as the byproduct. The second pathway occurs through 4 key steps: a) activation of the pyridine in the acidic media; b) ring

• -opening of the triazole moiety through a Dimroth rearrangement process affording 20 (reaction becomes instantly bright red); c) reduction of diazonium species to afford intermediate 21, observed by UV-LC–MS; and finally d) reductive cleavage of the -O–NH- bond, usually carried out under catalytic

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• -opening reactions (Scheme 11) [58]. The synthesis commenced with the smooth ring opening of the methyl-substituted lactone 90 using lithium bromide, which gave a single trans-cyclobutenyl bromide 91. Then, the bromocyclobutene 91 was submitted to further amide coupling and 4π electrocyclic ring opening to

• contradictions regarding the specific rotation values of inthomycin C and securely assigned the (3R)‑configuration for inthomycin C ((−)-3) [57]. In the synthetic studies towards racemic inthomycin C ((rac)-3), Maulide and co-workers investigated the stereoselective synthesis of halocyclobutenes and their ring

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

• -(amino)cyanocyclopropane derivatives not contaminated by intermediates or ring-opening byproducts [21], whereas the asymmetric Strecker synthesis induced by chiral amines was successfully conducted by sonication in the presence of silica gel [22]. Pursuing our interest in developing environmentally

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• rearrangement leads to p1•+ that further reacts by an inductive ring opening and α-cleavage to q1•+. Another α-fragmentation to r1•+ may be followed by a hydrogen rearrangement to s1•+ and two α-cleavages to t1•+, giving an alternative mechanistic explanation for the fragment ion at m/z = 312 by loss of C8–9

• rearrangement to a2•+ and a hydride shift to b2•+ (Scheme 3A). This hydride migration is in reverse order compared to a similar step along the cationic cyclisation cascade during the biosynthesis of 2 (Scheme S1 in Supporting Information File 1). The subsequent inductive ring opening to c2•+ and α-cleavage of

• inductive ring opening to v2•+, another hydrogen rearrangement to w2•+, and two α-cleavages to x2•+. Another hydrogen rearrangement and elimination of two hydrogen atoms lead to y2•+ which is identical to z1•+ in the fragmentation mechanism for the base peak ion of 1. Fragmentation mechanisms for

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• reactions of unsaturated compounds, e.g., alkene and enyne cross metathesis (CM [1] and EYCM [2][3][4]), alkene and enyne ring-closing metathesis (RCM and RCEYM) [5][6], ring-opening metathetic polymerization (ROMP) [7], etc., the CM and RCM are the most popular in organic synthesis [8]. Furthermore, the

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• cycloreversion, i.e., under the reaction conditions the adduct 3m may undergo a ring-opening with the liberation of the starting propenone 2f and the new isomeric azomethine imine B. The latter is able to isomerize into pyrazoline 4b or it reacts with propenone 2f leading to adduct 3f (Scheme 4). To prove this

• heterocycles, a mixture of substituted pyrazolines and corresponding pyrazoles was obtained [42], and also for the reaction with arylmethylidenemalononitriles [43]. It was assumed that the expected compounds initially had formed, but under the reaction conditions, they underwent a ring opening with the

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• moiety throughout (Scheme 3). Thus, the α,β-unsaturated ester 15 [25] was carried through a similar sequence to that previously described, i.e., dihydroxylation, cyclic sulfate formation, ring-opening with TBAF (although note the regioselectivity [31]), deoxyfluorination, and deprotection to deliver the

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• process, an alkene reacts with a halogen cation to form a halonium ion, which immediately undergoes ring opening by fluoride to form a vicinal halofluoride (see Scheme 1). The overall result is an anti-addition of the XF moiety (X = Cl, Br, I) across the double bond. Since many nucleophilic fluorine

• is the formation of only a single halonium ion intermediate is possible. According to the Fürst–Plattner rule (ring-opening into a chair conformation is preferred over a twist boat conformation), the formation of the products (rac)-2a,b is expected (Scheme 1). Indeed, halofluorinations of (rac)-1

• the absence of the reagent. It is also worth mentioning that the bromolactone (rac)-17a was surprisingly stable against lactone ring-opening: the compound remained intact after 20 hours of reflux in methanol in the presence of a catalytic amount of H2SO4. Presumably, the halogen cation attacks from

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• catalyst 15 to yield the trimerized products 12 (syn) and 13 (anti) in respectable yields (Scheme 2). The alkene-bridge exchange of 12 (syn) was accomplished by tandem ring-opening and ring-closing metathesis (ROM–RCM) in the presence of Grubbs’ first generation (G-I) catalyst to generate a C3-symmetric

• 27 in a single step. They also pointed out that when ethylene gas was used as an alkene source for the ring-opening step, diluted reaction conditions were necessary to dissolve the ethylene in dichloromethane to avoid polymerization. Therefore, after several experimentations, they noticed that liquid

• Z-oct-4-ene in toluene was found to be a more effective alkene source for the ring-opening reaction in comparison to the gaseous ethylene, as it increases solubility and also improve the lifetime of the catalyst. 2.1 Derivatization at benzylic position As can be inferred from the architecture of