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

• qualitative in situ screening of microbial colonies growing on solid agar medium, the compound (300 µg/mL) was incorporated into top agar, along with an α-ʟ-arabinofuranosidase from Thermobacillus xylanilyticus (TxAbf). This provided the means to reveal colored microbial colonies expressing the type A Fae

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• inhibitors in situ using 19F NMR spectroscopy (Figure 6). For this, the activity of the membrane-bound FAAH enzyme was evaluated by monitoring the hydrolysis of a fluorinated anandamide analogue ARN1203, a previously reported FAAH substrate, to arachidonic acid and 1-amino-3-fluoropropanol in the presence

• concentration, high sensitivity 19F NMR has been employed to offer unique opportunities for their sampling and characterization in situ [50]. Prosser et al. demonstrated the utility of this approach when employing a combination of variable temperature (VT) 19F NMR analysis and CD spectroscopy to study the near

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

• -dithiolate and dithiocarboxilate are trithiocarbonate salts. Synthesis and characterization of new o-quinone derivatives In this work we used sodium gem-dithiolates in the reactions with o-quinone 4. Alkali metal gem-dithiolates are relatively unstable species, so that they are commonly freshly prepared in

• situ from the corresponding active methylene compounds (Figure 1) [25]. In our syntheses we also used gem-dithiolates immediately, without isolation, except for the case when sodium trithiocarbonate (5a) was used. The reaction of 4 with 5a proceeds in DMF solution to give the corresponding 1,3-dithiole

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

• under these acidic conditions, hydrolysis of our py–OAt ether 15 would be accompanied by in situ deprotection of the Boc group to afford directly our final pyridin-2-(1H)-one products 16 and thereby eliminating a purification stage compared to the previous route. As literature was scarce for this

• hydrogenation [15], through addition of the hydride from triethylsilane to afford 1 after in situ hydrolysis of the triethylsilyloxy bond. HOAt alone does not degrade under these conditions and intermediate 21 has been identified and characterized from the reaction medium although we did not identify 2

• reaction mixtures were heated to 65 °C to complete the amide coupling reaction. For the least reactive anilines (e.g., compounds 24h,i), HATU only afforded trace quantities of the amide even at 65 °C. However, satisfactory results were obtained by generating the acid chloride in situ by adding a 3 fold

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

• , we have performed a number of different functionalizations of such cyclic systems with various complexity, and with a particular focus on the modification of sugar-derived lactams. As summarized in Scheme 1, this includes simple nucleophile addition to in situ-generated imines [23], the consecutive

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• of an alkyl electrophile has been reported to date [35]. This process used an umpolung strategy with activation of typically electrophilic perfluoroalkylsulfenamide reagents by iodide, releasing −SC2F5 or −SC3F7 anions in situ, which could then react with a selection of alkyl halides (Scheme 1b). In

• synthesis of BT-SCF3 from inexpensive 2-mercaptobenzothiazole (MBT) can be readily adapted to provide a wide range of different BT-SRF reagents. Moreover, in situ activation of the benzothiazolium salt by the alcohol provides a highly reactive alkyl electrophile, which can compensate for the inherently low

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• Stille coupling between oxazole vinylstannane 24 and dienyl iodide (rac)-20 as the final step. The synthesis began with alcohol (Z)-15a, which was readily prepared in 65% yield from propargyl alcohol (14) by using a copper(I)-catalyzed methyl Grignard addition followed by in situ iodinolysis. The Swern

• the corresponding primary amide, acetylation of acid 56a followed by acid chloride formation of acetate 56b and in situ ammonium hydroxide treatment was found to be fruitful to produce inthomycin B (+)-2 in reasonable yield (Scheme 4). This synthetic route introduced the chiral entry to any member of

• 90% yield. The transformation of acid (+)-73 to acetate (+)-76 using acetic anhydride in pyridine followed by acid activation with oxalyl chloride and then in situ treatment with 28% ammonium hydroxide afforded amide (−)-77 in 90% yield. Finally, deacetylation of (−)-77 using lithium hydroxide

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

• % overall yields. A relevant consideration in Holmes’s synthesis is: the nitrone is the same common intermediate as Gössinger’s [25], which is cyclized to form the tricyclic adducts. While the Gössinger route started from the cyclic 1-hydroxypiperidine, Holmes performed in situ cyclization to prepare the

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• . Metal-free nucleophilic trifluoromethylselenolations have been then performed with this in situ-generated anion. Perfluoroalkylselenolations have also been described. Keywords: fluorine; nucleophilic substitution; perfluoroalkylselenolation; selenium; trifluoromethylselenolation; Introduction Because

• ][46][47]. Very recently, we demonstrated that under reductive conditions, such compounds succeeded to perform nucleophilic substitutions [48]. In this reaction, the CF3Se− anion was in situ generated by reduction through a double electron transfer of 1a with TDAE (tetrakis(dimethylamino)ethylene

• substitution. This is adequate with the observed results. Noteworthy, the supposed formation of I2 was strengthened by the appearance of a red-brown color of the reaction media which faded after the addition of sodium thiosulfate. As demonstrated in the sulfur series [49], the in situ formation of an alkyl

Controlled decomposition of SF₆ by electrochemical reduction

• Sébastien Bouvet,
• Bruce Pégot,
• Stéphane Sengmany,
• Erwan Le Gall,
• Eric Léonel,
• Anne-Marie Goncalves and
• Emmanuel Magnier

Beilstein J. Org. Chem. 2020, 16, 2948–2953, doi:10.3762/bjoc.16.244

• degradation of SF6 [17][18]. Other elegant approaches have described the use of SF6 as precursor of reagent for fluorination or pentafluorosulfanylation. Very interestingly, the photochemical activation of this gas was described and allowed the in situ transformation of alcohols into alkyl fluorides [19][20

Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles

• Wenbo Huang,
• Kaimei Wang,
• Ping Liu,
• Minghao Li,
• Shaoyong Ke and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241

• –cyclization sequence of succinaldehyde and an in situ-generated arylimine, in which the succinaldehyde contributes three carbon atoms to the pyrrole ring. α,β-Unsaturated aldehydes have also been used as the C3 donor to construct pyrrole scaffolds [27][28]; (ii) [1 + 4] annulation, in which (hetero)arylamines

Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes

• Dmitrii A. Aksenov,
• Nikolai A. Arutiunov,
• Vladimir V. Maliuga,
• Alexander V. Aksenov and
• Michael Rubin

Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239

• approach, however, seems less attractive as it requires an additional step for the proper modification of the starting material. An alternative, more appealing method would capitalize on the in situ generation of a less sterically hindered, and therefore more reactive electrophilic nitronate. As we have

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

• approach using Et3N·3HF as an alternative to the DAST reagent. We controlled the stereochemistry of the nucleophilic fluorination at C4 of 1,6-anhydro-2,3-dideoxy-2,3-difluoro-4-O-triflate-β-ᴅ-talopyranose using Et3N·3HF or in situ generated Et3N·1HF. The influence of the fluorine atom at C2 on reactivity

• spectrum (470 MHz, CDCl3) of the crude reaction mixture of the fluorodeoxygenation using Et3N·3HF (entry 3 of Table 2). Next, decreasing the amount of Et3N allowed us to generate in situ Et3N·1HF (Table 2, entry 2) and Et3N·1.5HF (Table 2, entry 3). Using in situ generated Et3N·1HF, the mannose analogue 14

A heterobimetallic tetrahedron from a linear platinum(II)-bis(acetylide) metalloligand

• Matthias Hardy,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2020, 16, 2701–2708, doi:10.3762/bjoc.16.220

• ligand syntheses is the subcomponent self-assembly strategy [18][19][20][21][22][23]. Following this strategy, the actual ligand is generated in situ during the self-assembly process via reversible formation of covalent bonds, in most cases imine bonds. Despite this achievement, addressing even higher

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

• cycloaddition of in situ-generated azomethine imine under microwave conditions is described. The reaction of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones proceeds regio- and stereoselectively giving mostly good yields of the corresponding perhydropyrazolopyrazoles. The products of the

• AMIs can be generated in situ by thermal opening of any C–N bond of the diaziridine ring in 6-aryl-substituted 1,5-diazabicyclo[3.1.0]hexanes or 7-aryl-substituted 1,6-diazabicyclo[4.1.0]heptanes, respectively [16][17]. For the thermal generation conditions, the 1,3-dipolar cycloadditions of AMIs were

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• of dIno) in 10 mM Na-phosphate buffer (pH 7.4) at 22 °C for 6 h. Noteworthy, the formation of the 2'd-N7- and 2'd-N9-glycosides of N2-acetylguanine (AcGua) was observed in the transglycosylation of AcGua using dGuo/E. coli PNP (67.5 IU per 1 mmol base) for an in situ generation of dRib-1Pi (5 mM K

• reaction of OMG (Ara-U as a donor of Ara-1Pi) and 2-fluoroadenine [1-(β-ᴅ-arabinofuranosyl)cytosine (Ara-C) + cytidine deaminase for an in situ generation of Ara-1Pi], respectively, and the recombinant E. coli UP and PNP as biocatalysts in an one-pot mode. Unexpectedly, a significantly lower efficiency of

• formation of N6-benzylaminopurine riboside (BAPR; N6-benzyladenosine) was monitored by HPLC. A reference BAPR sample was obtained in 67% yield by the transglycosylation of BAP using a combination of guanosine and E. coli PNP to generate in situ Rib-1Pi (for the synthesis and NMR data, see Supporting

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

• decomposition upon reflux. In contrast, the treatment with trifluoroperacetic acid formed in situ in THF resulted in the expected allylic fluoride (rac)-33. Oxidative treatment under basic conditions, however, yielded the highly unsaturated diester (rac)-34, presumably via a base-promoted E1cB elimination of

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

• proceed via a stepwise approach with preformation of the corresponding iminium ion 85. The only catalytic example achieves the same transformation by generating 85 in situ but has reduced yields and enantioselectivities (82:18 er vs 92:8 er for stepwise). Alemán et al. reported that a similar reaction

• naphthoquinones 216 to afford enantioenriched benzofuranones 217 (Scheme 33) [93]. They then expanded the scope of the naphthoquinone by coupling this reaction with a photocatalysed oxidation of naphthols 218 to generate 216 in situ. While no detailed mechanism has been proposed, based on prior work of Hawkins et

• , which are photocatalytically generated in situ from redox-active esters 242 (Scheme 38) [99]. The mechanism advanced by Wang et al. proposes that 241 acts as a sacrificial reductant to generate the reduced photocatalyst, which can then reduce 242 in a second SET step to give α-amino radical 242• after

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• 5a at the lactone carbonyl group, and the product 4a, when o-aminothiophenol’s NH2 group attacked compound 5a at the lactone carbonyl group. The in situ formation of 5-phenylfuran-2,3-dione (5a) was indicated by the appearance of bright yellow color (characteristic for the 5-arylfuran-2,3-diones 5 [6

• acylpyruvic acid-based approach could be considered as a furandione-based one with in situ generation of furandiones 5. Since the acylpyruvic acid-based approach gave higher yields of the target compounds 3, we investigated its substrate scope by involvement of various acylpyruvic acids 2a–m and o

• available precursors, but produced more waste. The acylpyruvic acid-based approach can be considered as furandione-based one with in situ generation of furandiones 5. The BTAs 3 were formed together with the corresponding 2-hydroxy-2H-1,4-benzothiazin-3(4H)-ones 4, which can be interesting for pharmaceutics

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

• , entry 1). However, the addition of 2 equiv of boric acid drastically increased the arylation efficiency, with the yield of pyrimidone 3а reaching 86% (Table 2, entry 2). We assume that the boric acid added triggers the transesterification of phenylboronic acid pinacol ester 6а thereby leading to the in

• situ generation of reactive phenylboronic acid (2а). The reaction attempted at the lower (room) temperature and with lower amounts of copper acetate and pyridine practically failed to occur (Table 2, entries 3–5). In view of the availability of boronic acid pinacol esters, and particularly of

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

• to the trimethylsumanene synthesis, Sakurai and his co-workers selectively generated mono-, di- and trianions (29–31) using t-BuLi as a base and the formation of these sequential anions were confirmed by 1H and 13C NMR spectroscopy (Scheme 4) [32]. Next, the in situ generated trianion 31 was quenched

• using trifluoroacetyl nitrate which was in situ generated from conc. HNO3 and trifluoroacetic anhydride. On the other hand, formylation and acetylation were performed under microwave conditions at 130 °C using triflic anhydride and DMF or dimethylacetamide (DMA) to deliver the corresponding

• formation was observed. Therefore, they used a Pd-catalyzed carbonylative esterification in the presence of phenyl formate which in situ generated CO and phenol to provide the required product 97 in 73% yield (Scheme 24). In an independent work reported in 2017, Fukushima and co-workers detailed the

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

• previously for benzylic fluorination [130]. In a later perspective [36], the authors speculated that the amide served as a directing group. Indeed, in situ-formed ammonium carbamates were recently identified to direct the HAT of a quinuclidinium radical cation [208]. 3.5 Scalability of C–H fluorinations That

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• non-nucleophilic anions can be isolated [14][15], but in organic synthesis, they are most often generated in situ from suitable precursors and are directly exposed to diverse nucleophiles. Such transformations have been achieved using CH2(CF3)NR2 as the iminium ion precursors [15

Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination

• Yuqing Wang,
• Gaigai Wang,
• Anatoly A. Peshkov,
• Ruwei Yao,
• Muhammad Hasan,
• Manzoor Zaman,
• Chao Liu,
• Stepan Kashtanov,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2020, 16, 1963–1973, doi:10.3762/bjoc.16.163

• , a cinchona alkaloid derivative was allowed to react with an electrophilic fluorinating agent to afford an N-fluoroammonium salt of the cinchona alkaloid via transfer fluorination. In the second step, the Ugi adduct 8a was added to this in situ generated N-fluorocinchona intermediate to afford the

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• ). The 3-hydroxy group in 5 was then protected as a Nap ether through a TMSOTf-catalyzed one-pot reductive naphthylmethylation process [17][18], by which free hydroxy groups were first trimethylsilylated in situ with hexamethyldisiloxane ((TMS)2O) before being naphthylmethylated by treatment with 2