Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• -arabinofuranosides were significantly shortened (from 7 or 8 to 4–6 steps), and the transesterification yields were enhanced (from 46 to 73% and from 47 to 86%, respectively). This was achieved using enzymatic (immobilized Lipozyme® TL IM from Thermomyces lanuginosus) transesterification of unprotected vinyl

• molecule [12][15][16][17]. Additionally, the temporary protection of the functional groups is sometimes used during the synthesis in order to facilitate certain steps. Using an alternative approach, we employed a one-step regioselective transesterification of the unprotected vinyl ferulate 2 (synthesized

• ) displaying a hindered electron-withdrawing group. This led to a low target product yield (i.e., 5, 6, 8, and 9), a lower reactivity, and/or a higher hydrolysis of the vinyl ferulate into ferulic acid. Synthesis of ʟ-arabinofuranoside-free 4-nitrocatechol-1-yl–linker–ferulate chromogenic substrate 12 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

• O–H and N–H bonds of water, alcohols, carboxylic acids, and amines to form the observed products 121. 1,1-Difluoro-2-siloxy-2-vinylcyclopropane (122) was subjected to a fluoride-catalyzed ring opening to afford 1-fluorovinyl vinyl ketones such as 123. These compounds underwent a Lewis acid-catalyzed

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• preparation of 2H-azirines and their stereoselective transformation into highly functionalized NH-aziridines, starting from vinyl azides and organolithium compounds. The protocol has been developed using cyclopentyl methyl ether (CPME) as an environmentally benign solvent, resulting into a sustainable, safe

• of vinyl azides, or by other strategies involving oximes, imines and oxazoles [24]. One appealing strategy for the preparation of 2H-azirines involves the use of readily available vinyl azides [25][26][27][28][29][30]. However, the batch cyclization of vinyl azides into the corresponding 2H-azirines

• resulted in safer procedures for the preparation of 2H-azirines, offering valuable alternatives for production purposes. In 2013, Kirschning harnessed the photoinduced electrocyclization of vinyl azides in a microfluidic photoreactor yielding 2H-azirines as precursors of 1,3-dipolarophiles (Scheme 1a) [27

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• bromine in acetic acid, and then triethyl phosphite. Next, compound 28 was treated with sodium hydride followed by aldehyde 29 [37] to give (E,E)-dienyl stannane 30 in 50% yield. The key Stille coupling between 30 and vinyl iodide 31, prepared by Takai reaction [38] of phenylacetaldehyde, in presence of

• mixture of (Z,E)/(E,E)-36a, respectively). Aldehyde 35 was then converted into dibromide 37 using PPh3/CBr4 followed by stereoselective palladium-catalyzed monoreduction according to the literature available protocol [41] to give vinyl bromide 38 in 76% yield (Z/E as 99:1 mixture). Iodide 15a [42] was

• . J. K. Taylor and co-workers reported the first total synthesis of inthomycin B ((+)-2) using a Stille coupling of a stannyl-diene with an oxazole vinyl iodide unit followed by a Kiyooka ketene acetal/amino acid-derived oxazaborolidinone procedure as its cornerstones (Scheme 4) [43]. In the beginning

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

• in 65% yield and complete stereochemistry retention. When isocyanate (−)-84 was treated with copper chloride in water and THF, the (+)-euphococcinine (2) was obtained in 63% yield. A similar sequence was used to synthesize natural (−)-adaline (1, Scheme 10). In this case, vinyl iodide 86 was obtained

• -carboxaldehyde, 9:1 77a/77b, 67% (after chromatographic separation); ii) butyl vinyl ether, Hg(OAc)2, (10 mol %), sealed tube, 130–135 °C, 79%; iii) vinylmagnesium bromide, −78 °C; iv) Dess–Martin periodinane, 83% over two steps; v) Grubbs catalyst 2nd gen., CH2Cl2, reflux, 74%; vi) 1. (PhSe)2, NaBH4, EtOH; 2

• ; 2. 1-heptyne; 3. I2, THF, 82%; ii) 1. n-BuLi, Et2O, −78 °C to 0 °C; 2. p-menthyl-3-carboxaldehyde, 5:1 (−)-87a / (−)-87b, 50% (after chromatographic separation); iii) butyl vinyl ether, Hg(OAc)2, (10 mol %), sealed tube, 130–135 °C, 79%; iv) vinylmagnesium bromide, −78 °C; v) Dess–Martin periodinane

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

• selectflour to generate Ag(III)F. Subsequently, ethyl phosphite is oxidized by Ag(III)F to generate a P-centered radical (INT-I) and Ag(II)F. The electrophilic phosphonyl radical addition to the triple bond of 1a generates the vinyl-free radical INT-II, which is subsequently trapped by AgF(II) to afford the

• corresponding product 2a. The vinyl radical INT-II stabilizes the unpaired electron through resonance, and INT-II is more stable than INT-III [27][28]. Finally, we obtained the Z-configured product with respect to the aryl and phosphonyl groups. We also performed control experiments under standard conditions to

Amine–borane complex-initiated SF₅Cl radical addition on alkenes and alkynes

• Audrey Gilbert,
• Pauline Langowski,
• Marine Delgado,
• Laurent Chabaud,
• Mathieu Pucheault and
• Jean-François Paquin

Beilstein J. Org. Chem. 2020, 16, 3069–3077, doi:10.3762/bjoc.16.256

• ester derivatives. When using vinyl benzoate as the starting material, the desired compound 2g was obtained with a 75% yield with Dolbier’s protocol and an 84% yield with the DICAB protocol, while the addition product 2h was obtained with an 81% yield using Et3B as the radical initiator and 70% when the

Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD^®/Olah’s reagent under solvent-free conditions

• Yumeng Liang,
• Akihito Taya,
• Zhengyu Zhao,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2020, 16, 3052–3058, doi:10.3762/bjoc.16.254

• reaction of aryl, vinyl, and heteroaryl iodides with 2-(difluoromethoxy)-5-nitropyridine [18]. A wide variety of acyl fluorides were efficiently obtained in high yields. We were fascinated by the synthetic versatility of acyl fluorides [19] to form other functional groups during our research on acyl

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

• 64% yield over three steps. The conversion of 138 to sinensilactam A (20) was achieved in two steps. Platinum-catalyzed [3 + 2] cycloaddition The platinum-catalyzed intermolecular [3 + 2] cycloaddition of propargyl ether derivatives and vinyl ether producing polycyclic indoles was disclosed by

• Iwasawa and co-workers in 2011 [18][66] (Scheme 10A). Treatment of Boc-protected aniline 139 and n-butyl vinyl ether (140) with a platinum(II) catalyst afforded tricyclic indole 141 in 83% yield. The authors suggested that this catalytic [3 + 2] cycloaddition reaction may involve an α,β-unsaturated

• complex intermediate C. C is subjected to the nucleophilic attack of n-butyl vinyl ether (140) and generates alkenyl metallic intermediate D. Intramolecular nucleophilic attack onto the oxonium carbon of D affords the [3 + 2] cycloaddition product 141 with regeneration of the catalyst A. In 2020, Ye and co

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

• dihydropyrans bearing alkynyl and vinyl groups, a substitution of the allyl group for methallyl, acryloyl or methacryloyl resulted in the complete loss of reactivity or formation of highly complex mixtures. On the other hand, the reaction showed a significantly lower sensitivity to terminal modifications of the

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• like phenyl or isopropenyl at the bridgehead position were analyzed for the first time in different solvents and upon irradiation with different wavelengths. In all cases, a regioselective photoinduced 1,5-phenyl migration leading to vinyl ketenes from the more congested site of the molecule to the

• , the photorearrangement route is selectively from the α,β-enone part and we confirmed that the irradiation follows a type B rearrangement (Scheme 2) [16]. Another interesting set of competitive 1,5-(C–O) acyl shift rearrangements (formation of vinyl ketene) with that of 1,2-AS were observed when

• congested site of the molecule to the less one leading to the formation of vinyl ketenes 4c–e and 5b,d,f along with the formation of the 1,2-AS photoproduct 6a,d (Scheme 3, Table 1). Some of the vinyl ketenes were stable enough to be kept at room temperature up to 24 hours together as verified by time

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

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• ; potassium persulfate; thiazole; vinyl azide; Introduction Vinyl azide is one of the most versatile and potent building blocks explored in the synthesis of several heterocycles [1][2][3][4][5]. It can undergo photolysis or thermolysis to afford highly strained three-membered 2H-azirine, which can act as the

• -trisubstituted oxazoles 3. Reaction of vinyl azide 1 and 3 with ferric nitrate. Reactions were carried out at reflux temperature, using 1 (1 mmol), 2 (3 mmol), ferric nitrate (0.5 mmol) in acetonitrile (2 mL) for 6 h. Yields refer to the pure products after column chromatography. Optimisation studies.a Screening

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• produced 46. The hydrozirconation of 46 with Schwartz’s reagent under equilibrating conditions, followed by the reaction with I2 gave the vinyl iodide 47. Finally, the activation of the C-14 hydroxy group and the SN2 displacement with azide gave the C-8–C-16 fragment 48. Ghosh relied on a reductive

• of the C-6 stereocenter (Scheme 13) [15][16]. The administration of the vinyllithium reagent, generated from the addition of the vinyl bromide 80 to 79, gave a separable 1:1 mixture of the diastereomeric alcohols 81a and 81b. The undesired stereoisomer 81b was converted into 81a by a Mitsunobu

• [38][39] (Scheme 16). After a protecting group manipulation, the C-1 allyl group was truncated via ozonolysis, and the C-3 hydroxy group was transformed into an exocyclic methylene group to give 99. The conversion of the C-6 alcohol moiety to a vinyl group by oxidation and Wittig methenylation to give

Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines

• Ksenia I. Kaskevich,
• Anastasia A. Babushkina,
• Vladislav V. Gurzhiy,
• Dmitrij M. Egorov,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161

• establish from the 1H and 13C NMR spectral data. The signals of the vinyl proton of the uracil moiety are represented by quartets (4JHH = 1.4 Hz) in the δH 8.1 ppm region (quartet at δH 6 ppm for 6-methyl-5-oxo isomer). In the 13C NMR spectra, the signals of ethylene carbons of the uracil ring are presented

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• and the ability to target a larger variety of ions compared to e.g. glass. Plasticizers may be required to improve transmembrane diffusion rates unless the polymer is self-plasticizing. Plasticized poly(vinyl chloride) (PVC), which was used in this study, is an example of a commonly used membrane

• from poly(vinyl chloride) plasticized with bis(2-ethylhexyl)sebacate (DOS), which was chosen since it was considered to be suitable for use in membranes with monovalent primary ions [5]. The compositions of the ISMs were 2 wt % ionophore, 50 mol % anion exchanger relative to the ionophore, 65 wt % DOS

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• aromatic coupling partner, including frequently used Weinreb amides or functionalized secondary and primary amides. Regarding the scope of olefin substrates, the reaction tolerated numerous functional groups including acrylates, vinyl silanes or sulfones which was interesting from the post

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• inter- and intramolecular versions. Furthermore, the use of vinyl fluorides as olefinic counterparts had been completely overlooked. In this review, we collect the advances both on the stoichiometric and catalytic intermolecular and intramolecular fluoro-Pauson–Khand reaction, with special attention to

• groups at the vinylic position, very few examples have been described to date. In this context, our group recently explored the reactivity of 1,n-enynes bearing a vinyl fluoride moiety as the olefin counterpart in the intramolecular PKR [59] (Scheme 18). The study of the behavior of this kind of

• recovered, in agreement with previous precedents describing that trisubstituted alkenes are very unreactive substrates in this kind of process (Scheme 28) [65]. The influence of the introduction a vinyl fluoride moiety on the PKR was also investigated (Scheme 29). The resulting cyclopentenones 57 were

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• of such cases where an aryl radical, formed via the photocatalyzed reduction of diazonium salt 2.1+, added to methyl propiolate. Ensuing cyclization of the resulting vinyl radical 2.2· finally yielded the desired phenanthrene 2.3 [41]. A different approach involves the intramolecular cyclization of α

• -bromochalcones (Scheme 3). Thus, compounds 3.1a–d underwent a one-electron reduction by the excited photocatalyst fac-Ir(ppy)3. Upon bromide anion loss, the α-keto vinyl radicals 3.2·a–d were then formed, which smoothly added onto the vicinal aromatic ring in an intramolecular fashion, affording phenanthrene

• -obtained α-oxyalkyl radical intermediates were then trapped by biphenyl (or vinyl) isocyanides to afford functionalized phenanthridines, such as 9.3a (or quinolines) (Scheme 9, path a) [70]. A photogenerated nitrogen-based radical was likewise used to cleave the C–H bond α-to-nitrogen in amides to form the

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• Michael acceptor, as such is currently popular in the development of covalent inhibitors [43]. The reaction was carried out in the presence of 12 equiv BTMS at 35 °C. The disappearance of the signals originating from the vinyl protons (multiplets at δ 5.56–5.66 and 5.95–6.10 ppm) and the appearance of the

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• , cyclopentanone, and three carbon ring-expanded 1,3-diones from vinyl spiro epoxides [14]. The reaction is initiated by the addition of a thiyl radical to the vinyl epoxide 24, followed by the epoxide fragmentation to the alkoxy radical 25. Then, the β-cleavage to form the carbon-centered radical 26, the final

• expansion of vinyl spiro epoxides. Disulfide-catalyzed aerobic oxidation of diarylacetylene. Disulfide-catalyzed aerobic photooxidative cleavage of olefins. Disulfide-catalyzed aerobic oxidation of 1,3-dicarbonyl compounds. Proposed mechanism of the disulfide-catalyzed aerobic oxidation of 1,3-dicarbonyl

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• retention and inversion products [63] (Scheme 38). However, some olefins, such as cyclohexene, oct-1-ene, vinyl ether, vinyl sulfide, etc., produced 1,4-dithiane derivatives as products through the reaction of two molecules of thiobenzophenone (184a) and one molecule of the olefin under irradiation with 589

• 264 formed preferably, in the reaction of 256 with ethyl vinyl ether (215e) and propen-2-ylbenzene (186a). Notably, the photoreaction of 2,4-dithiobarbiturate 257 and 2,3-dimethylbut-2-ene (215a) produced exclusively the 4-thietane derivative 265 in 91% yield. 2,4,6-Trithiobarbiturate 258 reacted with

• stereocontrol were obtained when 316 was reacted with electron-rich olefins, as for example, vinyl ethers [87] (Scheme 58). In 2003, Sakamoto and co-coworkers investigated the intermolecular diastereoselective photo [2 + 2] cycloaddition of axially chiral monothiosuccinimides 319 which could enantiomerize into

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• tetrahydroindole skeleton) [32]. Any attempt to isolate or detect 17 during the trials turned out to be unsuccessful [35]. It is noteworthy that there have been almost no reports to date on the uncommon highly diastereoselective Diels–Alder reactions of analogous 2-vinyl or 3-vinylpyrroles [32], nor on the

• the solvent at 100 °C afforded pyrrolo[2,1-a]isoindoles 18a–c in good yields. This annulation process was regioselective, showing a preference of the cross-coupling reaction with the C-5 pyrrolic position and not with the vinyl moiety, which would give the dihydropyrrolo[1,2-b]isoquinoline 19. A

• ,b with maleimides 7b,c proved to be highly endo diastereoselective. This selectivity turned out to be significant in the case of vinyl benzopyrrolizine 18a as well. The consecutive Pd(0) cross-coupling reaction of some of the Diels–Alder adducts allowed for the synthesis of a numerous series of

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• of free radicals (Scheme 9). It remains unchanged [45] when dissolved in styrene (2 hours, 25 °C) or vinyl acetate (20 minutes, 60 °C; conversion of the oxime radical was less than 10% after 3 days at 25 °C). The inertness of the di-tert-butyliminoxyl radical with respect to the mentioned substrates

• involving an isonitrile group is the reaction of β,γ-unsaturated oximes 119 with vinyl isocyanides 120 to form substituted isoquinolines 121 (Scheme 39) [129]. Both α,α-disubstituted aromatic oximes (products 121a,b,e–h) and unsubstituted (R2 = R3 = H, products 121c,d) undergo the reaction successfully. The

• authors noted the effect of substituents in the phenyl fragment attached to the oxime group (R1): high yields were obtained with para- and meta-substituted substrates; however, when ortho-substituents were present, the product 121 was not observed. Two aryl groups at the vinyl fragment of the isocyanide