Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• mixture of mannosides α-3r and α-3s was obtained when cyclopropylmethanol (2r) was applied. The cyclopropylmethyl carbocation (C4H7+), which is generated in liquid SO2 medium, can undergo a rearrangement to form a cyclobutyl carbocation [68]. The latter can be trapped by a water molecule forming

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

• electrostatic interaction between carboxylate and iminium moieties undergoes a nucleophilic attack by isocyanide to generate nitrilium ion B. The intramolecular acylation of B forms C followed by Mumm rearrangement results in the formation of the desired products 22. The intermediate D may exist in equilibrium

• Michael addition of aminouracil to intermediate C to give D. Finally, desired product 90 is formed by intramolecular cyclization of intermediate D and subsequent rearrangement of E. 6.2.2 Pyridopyrimidines: Zhang and co-workers [84] proposed a synthetic route for the construction of substituted

• potential rearrangement explained the regioselectivity during ring closure as depicted in Scheme 44. Theoretically, two regioisomeric pairs of adenine (115, A) and isoadenine are possible (C, D) (Scheme 44). However, using the multicomponent approach one product, 4-amino-7-arylimidazo[1,2-a][1,3,5]triazines

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• ), and E (3e) comprising the pyrrolo[2,3-c]quinoline skeleton [25]. As demonstrated in Scheme 1, Curtius rearrangement of carboxylic acid 4 resulted in the formation of isocyanate 5, which, upon electrocyclization furnished pyrrolo[2,3-c]quinoline 6. Intermediate 6 was subsequently transformed into

• prepared from an appropriate carboxylic acid through a Curtius rearrangement reaction (50–98% yield). Treatment of urea derivatives 19a–d with CBr4, PPh3, and Et3N afforded carbodiimides 20a–d in 64–75% yield. Compounds 21a–d were obtained in situ following the removal of the TIPS protecting group in 20a–d

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

• reported. The sequence starts with a new tandem nucleophilic substitution/Brook rearrangement/single electron transfer-induced radical oxygenation furnishing orthogonally protected α,γ-dioxygenated N-allylamides with wide scope, mostly good yields, and partly good diastereo- and enantioselectivity for

• reactions providing functionalized pyrrolidones in high yields as diastereomeric mixtures. They converge to 3,4-trans-γ-lactams by base-mediated equilibration, which can be easily further diversified. Stereochemical models for both reaction types were developed. Keywords: Brook rearrangement; cyclization

• access to complex target molecules [74][75]. The principle is illustrated for a merger of nucleophilic opening of allylepoxides 1 with silylacetamides 2/Brook rearrangement [76][77][78] and oxygenation with TEMPO (3) leading to γ-(silyloxy)-α-(aminoxy)amides 5, which can be subsequently subjected to

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• open transannular bond (σ-homoaromatic structure) [79]. It was found that, as a rule, the [5,6]-open adducts formed initially can undergo rearrangement into [6,6]-closed isomers that are more thermodynamically stable. An alternative variant of [2 + 1] cycloadditions to the fullerene frame involves the

• C60 or b) possible formation of both isomers as a result of 1,3-dipolar cycloaddition of the diazo compound to the fullerene, followed by elimination of molecular nitrogen from the pyrazoline intermediate. Second, the rearrangement of [5,6]-open isomers into thermodynamically more stable [6,6]-closed

• chromatography (HPLC) (methanol/toluene as the eluent) to isolate a reddish-brown powder of methanofullerene 3 in 21% yield (Scheme 4). Similar to photolysis, the thermal rearrangement of kinetic products gives [6,6]-closed isomers that are thermodynamically more stable. After some time, the team of scientists

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• we recently discovered [32][33] a new synthetic pathway involving a rearrangement of 2-aryl-5-(2-aminophenyl)-4-hydroxy-1,3-thiazoles (e.g., 8aa–ad in Scheme 2) leading to the 3-[amino(aryl)methylidene]-1,3-dihydro-2H-indol-2-ones containing an unsubstituted amino group and the oxindole nucleus. In

• ) or leads to a complex and inseparable mixture of products (when starting from 2a,b). The addition of a base (e.g., triethylamine, N-methylmorpholine, ammonia) which was originally found to be beneficial [33] for the rearrangement of the kinetically formed thiazole to the desired product now caused a

• ., sodium borohydride, sodium cyanoborohydride, or sodium triacetoxyborohydride) in methanol. Unfortunately, formation of the desired N-acetyl-3-hydroxyoxindole was not observed at all, because a base-catalyzed addition of methanol to the C3=O and subsequent intramolecular rearrangement of the acetyl group

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

• of 1,1-dichloro-1-alkenones. The reaction scope was found to be broad, with various chain lengths and aryl substituents tolerated. For substrates containing an electron-rich aromatic ring, further reactions take place, resulting in bicyclic and/or rearrangement products. Keywords: aluminium

• trichloride; dichloroalkenes; Friedel–Crafts alkylation; rearrangement; trifluoroalkanes; Introduction 1,1-Dichloro-1-alkenes are valuable synthetic intermediates and have been employed in Pd-mediated cross couplings of one or both chlorine atoms [1][2][3][4][5][6][7], carbonylation reactions [8], and C–H

• form the 6,6-spirocycle 19. A 1,2-rearrangement would then produce the observed product 17. Presumably the analogous dichloroalkenone 6d does not undergo this cyclisation due to the deactivation of the ring by the ketone towards nucleophilic attack. Conclusion In conclusion, we have shown that 1,1,1

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

• flow process is presented that couples a Curtius rearrangement step with a biocatalytic impurity tagging strategy to produce a series of valuable Cbz-carbamate products. Immobilized CALB was exploited as a robust hydrolase to transform residual benzyl alcohol into easily separable benzyl butyrate. The

• species. This strategy thus highlights the applicability of this work towards the creation of important chemical building blocks for the pharmaceutical and speciality chemical industries. Keywords: biocatalysis; CALB; Curtius rearrangement; flow synthesis; reaction telescoping; Introduction Continuous

• into benzyl butyrate in view of facilitating the downstream purification of continuous flow Curtius rearrangement reactions [21]. In this paper, we will give a full account on this valuable approach and showcase the utility of the carbamate products towards generating sets of β-amino acid species

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• of 93%, the Pummerer rearrangement of sulfoxide 214 under harsh conditions turned out to be less efficient, affording 204f in only 42% yield. This reaction is thought to proceed stepwise via a first oxidative electron transfer, followed by deprotonation, a second oxidative electron transfer, and

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

• hydrogenolysis of benzyl ethers (H2, Pd) [72], DIBAL-H reduction of esters to form alcohols [73], oxidative cleavage of vinyl groups to form carboxylic acids (KMnO4) [74], and the conversion of the acids into amines using the Curtius rearrangement (SOCl2, followed by Me3SiN3, thermolysis, and acid hydrolysis of

• -difluorocyclopropanes (Scheme 40) [86]. Vinylcyclopropane rearrangements: O’Neal and Benson examined the influence of fluorine substituents on the kinetics of the vinylcyclopropane-to-cyclopentene rearrangement [87]. They noted the effect of an additional strain (approximately 5 kcal/mol per fluorine atom) in raising

• the kinetic reactivity of difluorocyclopropanes and lowering the temperature required for the rearrangement. Furthermore, another effect of the geminal substitution was a weakening of the bond opposite to the CF2 fragment by 8–10 kcal/mol. Dolbier et al. studied the thermal rearrangements of 2,2

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• (partly) disassemble in the formation of the assemblies with the polymer such that poly(allylamine) competes with the Flavy–photoacid interaction. The rearrangement that takes place then also shows that the interaction of the poly(allylamine) with Flavy and the photoacid is preferred. The competition

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

• -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

Tuning the solid-state emission of liquid crystalline nitro-cyanostilbene by halogen bonding

• Subrata Nath,
• Alexander Kappelt,
• Matthias Spengler,
• Bibhisan Roy,
• Jens Voskuhl and
• Michael Giese

Beilstein J. Org. Chem. 2021, 17, 124–131, doi:10.3762/bjoc.17.13

• after one heating/cooling cycle reveal the impact of the alkoxy chain length and a significant rearrangement of the solid-state packing upon heating/cooling the sample (diameter of sample ≈ 0.8 cm). Temperature-dependent fluorescent images of NO2-C9∙∙∙F4St showing the enhancement of emission upon

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• those experiments resulted in a rearrangement in the tetrazole ring, as shown in Scheme 4, upper path. We were able to obtain the desired aminotetrazole 9 by treating 3g with dry HCl at elevated temperature (Scheme 4, lower path). The resulting compound is particularly appealing, as similar scaffolds are

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• stereospecific semipinacol rearrangement in 78% yield over two steps. The resulting terminal alkene (−)-70 was submitted to Vacker's conditions to produce methyl ketone (−)-71 in 93% yield. The treatment of this ketone with potassium trimethylsilanolate induced a 1,5-Michael type reaction, via attack of tethered

• approach consisted of a 3,3-sigmatropic rearrangement to give an all-carbon quaternary center, a ring-closing alkene metathesis to give an 8-membered ring, and the use of a single enantiomer of p-menthane-3-carboxaldehyde to make two natural alkaloids of opposite configuration. Firstly, (+)-euphococcinine

• in a 9:1 ratio. After chromatographic separation, alcohol (−)-77a, isolated in 67% yield and >99% de was subjected to a Claisen rearrangement, leading to aldehyde (−)-78 in 79% yield (96% de determined by 1H NMR). (−)-78 was treated with vinylmagnesium bromide to give a mixture of allyl alcohols

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• Studi di Firenze, Via della Lastruccia 13, 50019 Sesto Fiorentino, Florence, Italy 10.3762/bjoc.16.255 Abstract The tandem gold(I)-catalyzed rearrangement/Nazarov reaction of enynyl acetates in which the double bond is embedded in a piperidine ring was computationally and experimentally studied. The

• of a triple bond, which has ultimately led to the total synthesis of several natural compounds [2][8]. The gold-catalyzed rearrangement of suitably substituted propargylic esters in particular provides a platform for cascade processes that involve a cationic or an allene intermediate generated in the

• first step [1][9][10][11][12]. In the framework of our studies on gold(I)-catalyzed reactions of propargyl alcohol derivatives [13][14][15], we have recently reported that the pentannulation of N-heterocycles [16] can be efficiently achieved by a cascade gold-catalyzed [3,3]-rearrangement/Nazarov

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• tetracyclic compound 56. Dihydroxylation of freshly prepared 56 with OsO4 and then selective tosylation afforded 57 in 39% yield over two steps. Exposure of 57 to DBU upon heating gave the elimination product 58, which was subjected to an oxidative rearrangement with PDC to give enone 59 in 68% yield. Copper

• rearrangement product 99 in 85% yield. The synthesis of daphenylline (11) was completed by a seven-step synthesis from benzofuran 99. Phosphine-catalyzed enantioselective [3 + 2] annulation In 2019, Lu and co-workers disclosed a novel chiral-phosphine-catalyzed enantioselective [3 + 2] annulation of allenes and

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

• Truce–Smiles rearrangement in aryl sulfonamides and aryl phenylsulfonates [44][45][46] or the [3,3]-sigmatropic rearrangement of sulfonium salts arising from the reaction of aryl sulfoxides and phenols [47]. To overcome this problem, the use of a metal catalyst (mainly Ni) was mandatory as reported for

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• thioamides with alkyl- and arylsulfonyl azides. For each type of thioamides a reliable procedure to prepare N-sulfonyl amidines in good yields was found. Reactions of 1-aryl-1,2,3-triazole-4-carbothioamides with azides were shown to be accompanied with a Dimroth rearrangement to form 1-unsubstituted 5

• -arylamino-1,2,3-triazole-4-N-sulfonylcarbimidamides. 2,5-Dithiocarbamoylpyridine reacts with sulfonyl azides to form a pyridine bearing two sulfonyl amidine groups. Keywords: amidines; Dimroth rearrangement; isoxazoles; sulfonyl thiazoles; thioamides; 1,2,3-triazoles; Introduction The biological activity

• Beckmann reaction of oximes with p-toluenesulfonyl azide [34], the sulfonyl ynamide rearrangement by treatment with amines [35], the sodium iodide catalyzed reaction of sulfonamide with formamide [36], and the condensation of sulfonamide derivatives with DMF–DMA [37]. A few representatives of N-sulfonyl

Fluorine effect in nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-D-hexopyranose

• Danny Lainé,
• Vincent Denavit,
• Olivier Lessard,
• Laurie Carrier,
• Charles-Émile Fecteau,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2020, 16, 2880–2887, doi:10.3762/bjoc.16.237

• core, would be suitable for the C4 deoxyfluorination of intermediates 2–5. However, it is well documented that undesired rearrangement products with 1,2-aglycone migration [26][27][28] or skeletal rearrangements [29] have been observed during fluorodeoxygenation of glycopyranosides with DAST

• fluorine electron density to attack equatorially. Although we propose an oxiranium intermediate for the C4 deoxyfluorination of 13, we did not observe any ring rearrangement, typically as a result of ring contraction (for example, compound 19, step d) [26][29][38]. Also, we did not observe any 1,2-alkyl

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• rearrangement after the protonation of 1 and 2 furnished exclusively the two complexes [(1•H+)(3)] and [(2•H+)(4)] (Figure 3). The reduced affinity of the cucurbit[7]uril toward the protonated diethylamino-substituted guest in combination with the concomitant increased binding for the dimethylammonium

• hydrogen-bonded octameric and tetrameric tubes. (c) A representation of the complex mixture after combining the monomers 5 and 6 in CDCl3. (d) The partial separation of the mixture upon the selective C60 complexation by monomer 5. The guest-induced rearrangement results in an incomplete self-sorted mixture

• (2019) American Chemical Society. Cyclic metallosupramolecular transformations. Fully reversible multiple-state rearrangement of metallosupramolecular architectures depending upon copper(I) stoichiometry. Reproduced from [65]. The selective encapsulation and sequential release of guests in a self-sorted

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

• through reactions that are classified as σ-bond cleavages, α-fragmentations, inductive cleavages, McLafferty rearrangements [11], retro-Diels–Alder fragmentations [12][13], and the recently observed unusual radical-induced retro-Cope rearrangement (herein, “retro” indicates that the mass spectrometric

• energetically more feasible process may be represented by an inductive cleavage leading to b1•+, a hydrogen rearrangement to c1•+, and an α-cleavage to d1+ (Scheme 1B). The formation of the fragment ion at m/z = 312 proceeds through a highly specific loss of the C8–9 portion of 1. This is explainable from b1

• group C23 results in j1+ (Scheme 1E). The fragmentation of the C25–3–4 portion can be explained starting from 1•+ by a hydrogen rearrangement to k1•+ and α-cleavage to l1•+ (Scheme 1F). Another hydrogen rearrangement combined with an α-fragmentation then leads to the allyl cation m1•+ which may undergo

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• formed from hedycaryol (7) during GC/MS analysis by a Cope-rearrangement [20][21], indicating that 7 might be originally present in the hairpencils. That said, we cannot disprove that this rearrangement could also occur in the androconia. Hedycaryol is an early product of sesquiterpene biosynthesis

• in the region around the acylium ions. Monounsaturated prenyl esters show the elimination of C5H10 (M − 70, m/z 280 in A), likely formed by rearrangement of an allylic H to the carbonyl group, followed by H-transfer (Figure 3C). Furthermore, the prenyl group can be lost (M − 69, m/z 281) and the

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• rearrangement of the pseudo[2]rotaxane into a non-threaded complex as discussed above. As dethreading is impossible in NDIRot, the electrochemical data are significantly different from those of the non-threaded complexes formed from the pseudorotaxane and the (CH3)2NH2PF6 complex of NDIC8. The optoelectronic

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

• involved a rearrangement, providing the isomeric products (rac)-20a and (rac)-21a (Scheme 12). We also observed the formation of the dibrominated compound 22, which became the sole product when the reaction was performed under reflux conditions. Iodofluorination was much less effective: even after repeated

• isomeric halofluorination products can be explained by the preferred formation of the halonium ions T6a–c, respectively, since the halogen cation attacks the C=C bond of the imide 19 from the less hindered side, followed by rearrangement into the intermediates (rac)-T7a–c, respectively. For epoxides and