N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• important tool in the asymmetric synthesis of aziridines [25][26], α-amino acids [27][28], β-amino acids [23][29] and branched α-amines [30][31]. The Darzens-type asymmetric synthesis of N-(p-toluenesulfinyl)aziridine 2-carboxylate esters (7 and 8) was described through the addition of lithium α

• successively into β-amino esters 51, and the corresponding β-lactams 52 with high optical purity (Scheme 17) [89]. The absolute configurations of compounds 52 were obtained by the comparison of the signs of specific rotation of 52 with R = Ph(CH2)2, with that of known (R)-4-(2-phenylethyl)azetidin-2-one. A 6/4

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

• DAST [22][25][26][30][35], or reaction of C3/C4 methanesulfonate or trifluoromethanesulfonate esters with a source of nucleophilic fluorine, such as TBAF or KF [22][25][34]. Although these fluorinations usually proceeded with inversion of configuration, the acetylated 3-fluoro-GlcNAc analogue was most

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• relatively inexpensive, useful reduction reagent for developing new green synthetic transformations [6][7][8][9][10][11][12]. Compared to other bioinspired reagents, such as Hantzsch esters, AB represents a more convenient reagent that generates much less waste [10]. We have recently reported the use of

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

• efficiency for simple substrates, like the synthesis of 1-mexyl-5-phenylbiguanides described by Lebel et al. (Scheme 16A) [46]. However, the presence of hydrolysis sensitive functions like esters usually leads to an understandable drop in yields (Scheme 16B) [47]. A microwave-assisted version of this

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• 30 min of reaction and dibrominated 2h′ was afforded as the major product after 18 h. Similarly, 1,3-dimethyladamantane (1i) and methyl adamantane-1-carboxylate (1j) were successfully converted to brominated products 2i and 2j, respectively. For benzeneacetic acid methyl esters 1k, 1l and 1m, the C

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• prochiral diol esters. The enzyme reacts enantiospecifically with the ester to release a chiral product, leaving the acyl group attached to the active site. In a second stage the achiral acyl group undergoes hydrolysis by water. In the desymmetrisation of diols (and diacids, below) kinetic amplification can

• , both”. Followed in most lipase or esterase reactions of prochiral diacids: either hydrolysis of their esters, or esterification of the free acids. The enzyme reacts enantiospecifically with the ester or acid. But now the acyl enzyme can be in either stereoisomeric form, so the kinetics are different

• on the product ee at 95% of equilibrium conversion: k2, k2/k4R, E · k4S/k4R, k−1/k2, k3R/k−4R, k3S/k−4S. Behaviour for “ping-pong, first” kinetics This model will normally apply in enzymatic hydrolysis of prochiral diol esters, so simulations were run for the case where the second substrate (H2O in

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• transformation into diastereomers by esterification with chiral acid chlorides [19][20] as well as the kinetic resolution (KR) of racemic esters of 2 via an enzymatic hydrolysis [25][26][27] were very successfully used to access enantioenriched 2. Recently, Akiyama and co-workers reported the kinetic resolution

• rac-2 with anhydride 4aa. Supporting Information Supporting Information File 70: Copies of NMR spectra and HPLC chromatograms as well as analytical data of esters 3 obtained with the alternative acyl-transfer reagents 4. Acknowledgements We are grateful to Thomas Bögl (Institute of Analytical

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• , cyanides, esters, ethers, halides, and heterocycles, and various α-aminoketones (32 examples) can be yielded in 90% isolated yield. According to the author, the EDA complex had a six-membered-ring transient state, and the imine also acted as an organic base (abstracting proton from α-keto acid), proving

• -protected amines, have been efficiently transformed to suitable pinacol boronic esters. This simple operation without transition-metal catalysis will be widely promoted in the synthesis of important boron-containing molecules in medicine and biology. In 2019, Aggarwal and colleagues [55] proposed that the

• protocol reveals a high functional-group tolerance that permits the transformation into boronic esters of natural alcohol products with high stereocontrol. The construction of C–N bonds The development of efficient methods to construct C–N bonds is an essential scheme in organic synthesis due to its

[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

• acid esters 87–97 with various alkyl-chain lengths were synthesized (Scheme 28). According to reference [113], the solubility of C60 derivatives in organic solvents increases with an increase in the length of alkyl substituents. The photovoltaic devices designed using poly(3-hexylthiophene

• methanofullerenes via tosyl derivatives. (BtOH is 1H-benzotriazol-1-ol.) The synthetic route to [60]PCBM via tosylhydrazine. The reaction mechanism of fullerene cyclopropanation via tosylhydrazine derivatives. Serial synthesis of [6,6]-phenyl-C61-butyric acid esters 87–91 [114], 92–96 [113][115], and 97 [116

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

• of 6 equiv of 1,1,3,3-tetramethyldisiloxane (TMDS) led to the total conversion to propane and polydimethylsiloxane (PDMS), a silicon oil with several applications (lubricants, food-additives, breast implants). 3.2.3 Other polyesters: The hydrogenolysis reaction of esters other than PET and PLA was

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

• *) [4]. The structural analysis of the diastereomeric menthyl esters obtained after chiral resolution was conducted based on a combination of NOESY data and conformational calculation in that study [4]. In this study, the configurational analysis of the menthyl ester is reasonably justified by X-ray

• only a monocarboxylic acid product, and the menthyl ester remained unaffected (structure not shown). Fortunately, the complete deprotection of the two esters was cleanly possible under acidic conditions (6 M aq HCl, 1,4-dioxane, 75 °C, 4 days) to furnish (2R)-MC-27 (4) in 48% yield (Scheme 3), the

• yield (28%). The carboxylic acid (rac)-19 was then esterified with ʟ-(−)-menthol (8) for a chiral resolution. The reaction was mediated smoothly by MNBA [9] in 85% yield to give a diastereomeric mixture of menthyl esters 20* and 20 after silica gel column chromatography. As shown in Figure 6, the clean

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

• ). Alternative electrophilic components for the Eschenmoser coupling reaction The Eschenmoser coupling reaction [36][37] usually starts from α-substituted ketones, esters, malonates, or nitriles. The group in the α-position must be a good leaving group enabling a facile nucleophilic substitution giving the α

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• reviewed, including the phosphonylation of hydroxy esters with phosphonochloridates, the condensation of phosphonic monoesters and hydroxy esters, the alkylation of phosphonic monoesters with 1-(alkoxycarbonyl)alkyl halides or sulfonates, multicomponent condensation of amides, aldehydes, and

• dichlorophosphites followed by alcoholysis with hydroxy esters, the phosphinylation of hydroxy esters with phosphonochloridites followed by oxidation, and the carbene insertion of N-protected amino acids with 1-diazoalkylphosphonates. This review includes the synthesis of α-, β-, and γ-phosphonodepsipeptides and

• phosphonylation of hydroxy esters 2 with N-protected aminoalkylphosphonochloridates 3 (method I), reactions of N-protected aminoalkylphosphonic monoesters 4 with hydroxy esters 2 (method II) or with 1-(alkoxycarbonyl)alkyl halides or sulfonates 5 (method III), pseudo-four-component condensations (method IV), and

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• biologically attractive trifluoromethyl ketones from readily available methyl esters using the potent greenhouse gas fluoroform (HCF3, HFC-23) was developed. The combination of fluoroform and KHMDS in triglyme at −40 °C was effective for this transformation, with good yields as high as 92%. Substrate scope of

• the trifluoromethylation procedure was explored for aromatic, aliphatic, and conjugated methyl esters. This study presents a straightforward trifluoromethylation process of various methyl esters that convert well to the corresponding trifluoromethyl ketones. The tolerance of various pharmacophores

• compounds to trifluoromethyl carbinols because it does not require any expensive reagents nor very low-temperature conditions. Although the reaction has a broad substrate scope of embracing ketones, chalcones and aldehydes, the transformation of esters to trifluoromethyl ketones by this protocol was never

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• ) in the teraryl structure, because the diborylated arenes were less available. Either (a) the coupling of boronic acid esters bearing one acetal moiety with dihalogenated arenes or (b) the coupling of dihalogenated arenes bearing two acetal moieties with arylboronic acids were conducted for the

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• , irrespective of the site of activation, the subsequent ejection of the activating reagent would generate an extended iminium ion whose capture by adventitious water would produce legonmycin A directly. For context, the treatment of enol esters with oxidizing agents to give α-hydroxyketones, or halogens to give

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

• natural or synthetic compounds [9][10]. The latter, which are used in high-throughput screening (HTS) assays, fall into three categories. The simplest are feruloyl esters of chromogenic moieties [11][12][13][14], such as p-nitrophenol or short-chain alkyl groups (e.g., methyl ferulate). More elaborate and

• ][20], and their use involves a challenging tandem reaction [21]. Finally, the synthesis of other, more generic esters that can be used to assay esterases, including Faes, and lipases have been reported [22][23]. In this work, we revisit the preparation of simple feruloylated substrates, such as the 5

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

• major advantages of 17 over 12 are that the bromo derivative 17 is stable at room temperature and requires a lower temperature than 12 to decompose to difluorocarbene. By the use of BrCF2COONa in diglyme at 150 °C, various alkyl- and aryl-substituted alkenes, allyl alcohol esters, α,β-unsaturated esters

• was found to be superior to both CsF and KF as an initiator. Difluorocarbene generated from TFDA (25) also readily reacted with propargyl esters 27 at the triple bond (Scheme 13). The difluorocyclopropenes 28 were further converted into the difluorocyclopropyl ketones 29 by alkaline hydrolysis and

• 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

Selective synthesis of α-organylthio esters and α-organylthio ketones from β-keto esters and sodium S-organyl sulfurothioates under basic conditions

• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Thiago Barcellos,
• Claudio C. Silveira and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2021, 17, 234–244, doi:10.3762/bjoc.17.24

• 10.3762/bjoc.17.24 Abstract We described herein a selective method to prepare α-organylthio esters and α-organylthio ketones by the reaction of β-keto esters with sodium S-benzyl sulfurothioate or sodium S-alkyl sulfurothioate (Bunte salts) under basic conditions in toluene as the solvent at 100 °C. When

• 4 equivalents of a base were used, a series of differently substituted α-thio esters were obtained with up to 90% yield. On the other hand, employing 2 equivalents of a base, α-thio ketones were achieved after 18 h under air. Furthermore, after a shorter reaction time, the isolation of keto–enol

• tautomers was possible, revealing them as significant intermediates for the mechanism elucidation. Keywords: α-alkylthio esters; α-alkylthio ketones; Bunte salts; C–C bond cleavage; β-keto esters; Introduction During the last ten years, sodium S-organyl sulfurothioates, also known as Bunte salts, were

Decarboxylative trifluoromethylthiolation of pyridylacetates

• Ryouta Kawanishi,
• Kosuke Nakada and
• Kazutaka Shibatomi

Beilstein J. Org. Chem. 2021, 17, 229–233, doi:10.3762/bjoc.17.23

• achieved using N-(trifluoromethylthio)benzenesulfonimide as the electrophilic trifluoromethylthiolation reagent. The reaction afforded the corresponding trifluoromethyl thioethers in good yield. Furthermore, the preparation of lithium pyridylacetates by saponification of the corresponding methyl esters and

• of methyl esters and subsequent decarboxylative fluorination (Scheme 1a) [21]. Herein, we describe the application of this method to decarboxylative trifluoromethylthiolation with an electrophilic trifluoromethylthiolation reagent (Scheme 1b) [22], which enables easy installation of the

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• to optimize the Cl→N3 SNAr process at the purine C2 position, and that way, the isopropyl phosphonate 2b was also obtained. It is known that both chloride and azide can cleave phosphonate esters [25][26][27][28], but the chloride source would not interfere with the SNAr process at C2. Hence, we

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

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

• others were finally resolved in this work. Subsequently, the Hatakeyama team converted their authentic (+)-82 into the (R)- and (S)-MTPA Mosher esters which provided well-matched NMR data to Hale’s previous synthesis [60]. Upon further purification using flash chromatography, the Hatakeyama team re

• rotation value of inthomycin C ((−)-3) and re-investigation of their (R)- and (S)-MTPA esters, Hale and Hatakeyama jointly concluded that Ryu and others had indeed synthesized (3R)-inthomycin C ((−)-3). Two years later, Reddy and co-workers accomplished enantiospecific formal syntheses of both inthomycins

• expected alcohol (−)-140 was obtained in 93% ee and 72% yield. Compound (−)-140 was further transformed to the corresponding Mosher's esters and their NMR and X-ray crystallographic data were well-matched with the (R)-stereostructure of (−)-140 [77][78]. The hydroxy group of (−)-140 was protected as

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

• 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

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

• corresponding amides 4a–d by treatment with phosphorus decasulfide (Scheme 1). It is worth noting that amides of 1-alkyl-1,2,3-triazole-4-carboxylic acids are poorly represented in the literature and the methods of their preparation require the addition of alkyl azides to acetylene carboxylic esters and