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

• examined [46]. Trifluoromethyl ketones (TFMKs) are valuable fluorine-containing synthetic targets of bioactive compounds [55][56] that behave as mimics of the tetrahedral transition-state intermediate of enzymatic hydrolysis of esters and amides by stabilizing their hydrates (Figure 1a) [57]. In fact, 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

• smooth hydrolysis. Wang et al. reported the enantioselective biotransformations of geminally difluorinated cyclopropanecarbonitriles and amides in 2004 [77]. They transformed gem-difluorocyclopropane derivatives with the help of a soil microorganism, Rhodococcus sp. AJ270, which provided a very effective

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

• to α-sulfenylated amides (Scheme 1C) [52]. Inspired by those elegant pioneering studies, we explored the reaction of 1,3-dicarbonyl compounds with Bunte salts mediated by a base (Scheme 1D). The choice of NaOH as the base and its concentration were crucial to the selective synthesis of α-thio esters

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• amides 1a,b and 2a,b. Initially, by refluxing diamide–diamines 1a,b and cyclam amide precursors 2a,b in THF with LiAlH4 for 3 days [36], complex product mixtures of partly and fully reduced species were obtained for all amides except 2a. In order to activate the amides for reduction, improved reaction

• cyclam tetraamino-coordination was obtained by 1H,15N-HMBC NMR. The polyamides (1, 2) failed to undergo Au(III) coordination, which confirmed the previously observed resistance of amides to coordinate to Au(III). The catalytic ability of the new Au(III) complexes were screened in selected test reactions

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

• % isolated yield (Table 1, entry 6). With these conditions in hand, we prepared a small library with different amides at C-3 to test the robustness of this new process before going into library production (Table 2). However, to our surprise, the process worked only for compounds with aliphatic amides at C-3

• affording only acceptable yields of pyridine intermediate (9a–c) with the major byproduct arising from the dechlorination of 8. Application of the same conditions with aromatic amides at C-3 (8d,e) failed with only trace quantities of final product observed. We speculated that the aromatic carboxamide NH

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

• . Although the Vilsmeier–Haack reaction [1] or amide reduction with LiAlH4 are textbook examples that easily come to mind, there are not many other methods available. Simple alkyl and aryl amides, unlike other carbonyl compounds, typically do not undergo direct addition by a nucleophile, including active

• review articles have been written about this topic, enclosing most of the advances made to date [3][4][5]. A fascinating subset of these transformations encompass the reduction of amides to imines, with direct subsequent functionalization. One of the methodologies for such a modification was developed by

• Charette et al. In their procedure the combination of triflic anhydride and pyridine [6] (or its 2-fluoro derivative [7]) was used as an activating agent to transform amides into reactive iminium complexes. Another stoichiometric approach was presented by Georg et al. by utilization of zirconocene chloride

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

• -sulfinimes (+)-95 and (+)-96 were added to a −78 °C solution of the N-methoxy-N-methylacetamide enolate 102, leading to Weinreb amides (+)-97 and (+)-98, respectively, with good yields and high diastereoisomeric excesses (Scheme 11). The reaction of (+)-97 and (+)-98 with five equivalents of methylmagnesium

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

• hydrogen reservoirs [40], as reducing agents in various transformations, including the reduction of aldehydes, amides and ketones, reductive aminations, alkene hydroboration, and carbon bond forming reaction [41][42], as well as various boronate and borinic acid precursors [43][44][45][46][47]. More

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

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

• Tetsuya Sengoku,
• Koki Makino,
• Ayumi Iijima,
• Toshiyasu Inuzuka and
• Hidemi Yoda

Beilstein J. Org. Chem. 2020, 16, 2769–2775, doi:10.3762/bjoc.16.227

• the optimal reaction conditions for electrophilic allylation of 2b with 1a in hand, we turned to demonstrate the versatility of this method. In our previous work relating to nucleophilic allylation of imide derivatives, we succeeded the syntheses of N-carbonyl-functionalized γ-hydroxy amides bearing

• transposed reaction sequence, N-Boc protection followed by hydroxylation (Scheme 2). N-Boc amides were readily obtained by treatment of 3b–o with Boc2O and DMAP, which were successively subjected to hydroxylation in the presence of CuBr. Expectedly, the desired lactonization occurred spontaneously under 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

• -workers have recently described a method for the one-step, diastereoselective 1,2-difluorination of alkenes, mediated by a hypervalent iodine catalyst [24]. The substrate scope of the Jacobsen method has certain constraints but their original report did include some examples of α,β-unsaturated amides, and

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• achieved by expression in minimal media in the presence of 15N ammonium salts. A 1H,15N-HSQC spectrum shows all N–H correlations that are moderately stable and do not exchange with the solvent water too quickly, which includes the amide NHs and some side chain NHs, e.g., the side chain amides of asparagine

• and glutamine as well as the indole NH of tryptophan and some of the arginine NHε. This spectrum is also known as an amide finger print spectrum of a protein because the chemical shifts of the amides are very sensitive to both the secondary and tertiary structure. The amide signals, particularly for

• signals and/or decrease in relative intensity due to line broadening can be observed for amides in close vicinity of the binding site. Both the 1H and 15N chemical shifts of any given amide can change upon ligand binding, whereby the magnitude and direction of 1H and 15N shifts are independent. The

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

• gadolinium catalyst and chiral ligand L2 (Scheme 43b) [108]. By altering the radical precursor to α-silyl amines 277 and using α,β-unsaturated amides 278, Yoon et al. found that the reactions could be stopped at the RCA step to give enantioenriched 1,4-addition products 279 using a scandium catalyst and

• enantioselectivities (11 examples, up to 98:2 er). While a chain propagation mechanism is possible, the quantum yield of the reaction is <1 (Φ = 0.046), so a closed cycle is likely the dominant mechanism in this case. Another recent example of this type of reactivity was developed by Xu et al. using amides 299 in a

Three new O-isocrotonyl-3-hydroxybutyric acid congeners produced by a sea anemone-derived marine bacterium of the genus Vibrio

• Dandan Li,
• Enjuro Harunari,
• Tao Zhou,
• Naoya Oku and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1869–1874, doi:10.3762/bjoc.16.154

• methyl ester (PGME), was conducted [10]. The compounds 1–4 were derivatized with (S)- or (R)-PGME by the action of N,N´-diisopropylcarbodiimide (DIC) and N,N-dimethylaminopyridine (DMAP) in CH2Cl2, followed by reversed-phase HPLC to give the respective (S)- or (R)-PGME amides 1a, 1b, 2a, 2b, 3a, 3b, 4a

• mg; tR 9.8 min). Preparation of the (S)- and (R)-phenylglycine methyl ester amides To a solution of 4 (1.7 mg, 10 μmol) in anhydrous CH2Cl2 (0.5 mL) in a dried vial were added (S)-phenylglycine methyl ester (PGME, 3.3 mg, 16.4 μmol), DMAP (1.2 mg, 10 μM), and DIC (3.0 μL, 19.5 μmol), and the mixture

• (10 × 250 mm), eluted by a gradient method (MeCN/0.1% HCOOH) at 4 mL/min, with monitoring at 254 nm, to give the (S)-PGME amide 4a (2.9 mg, 93%) as colorless oil. The PGME amides 1a/b–3a/b and 4b were prepared by the same procedure but replacing the starting material and the chiral reagent accordingly

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• its analogues towards trans- and cis-amides [81]. An unsubstituted proline residue usually exhibits a preference to form a trans-amide. Fluoroprolines are notorious for the relative stabilization of the amide rotamers depending on the stereochemistry at the C4-atom. This is known as the chiral bias

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• multicomponent reaction of rare-earth metal amides [28], the reaction of CO2 with propargylamines or aziridines [29][30] and the cycloaddition reaction of epoxides with isocyanates [31][32]. On the other hand, for the synthesis of five-membered cyclic carbonates, the cycloaddition of CO2 to epoxides, the

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

• variety of benzamides bearing different substituents at the ortho- and para-positions gave the products in good to excellent yields, while the meta-substituted substrates were converted into a mixture of two isomeric products. Moreover, amides containing heterocycles such as thienyl, pyrazolyl, pyridyl

• photocatalyst Ru(bpy)3Cl2·6H2O and Pd(OAc)2 promoted the formation of the coupling products in high yields when the reaction was irradiated with visible light. This new procedure exhibited a good functional group tolerance and turned out to be compatible with a wide range of DGs, including amides, pyrazoles

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

• -propargyl-N-[2-(trifluoromethyl)allyl]amides 24 were treated with dicobalt octacarbonyl to afford the cobalt alkyne complex, which was then heated in CH3CN. Under these conditions, trifluoromethylated cyclopentenone 25a was obtained in high yield (81%) and diastereoselectivity (anti/syn = 94:6) (Scheme 11

• ring-fused cyclopentenone 25d in both lower yield (53%) and lower diastereoselectivity. A catalytic PKR of fluorinated 1,7-enyne amides 26 using catalytic amounts of [Rh(COD)Cl]2 was reported in 2008 by Hammond and co-workers [52]. The authors concluded that the reaction was highly sensitive to

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• Lewis base upon ligand exchange (Figure 5) [56]. This working hypothesis may also rationalise the deletion experiment (10), the recalcitrance of acetyl derivatives, and the striking reactivity disparity between amides (12/13) and the phthalimide derivative 16. Finally, to investigate the fate of water

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• , carboxyl groups, amides, amino acid side chains), our DCL should be applicable to a similar scope. In order to show that our system offers a general approach to find binders for biomolecules in water we choose to test our DCL against peptide templates. Results and Discussion We started from our established

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• macrocycle-thread hydrogen bonds, thereby reducing self-aggregation. To this end, a five-component clipping strategy was adopted using different tetrabutylsuccinamide threads (Figure 2) with varying hydrogen-bond basicity (amides > esters) [4][15]. Threads containing an ester group were selected as esters

• macrocycle–thread hydrogen bonds, with the other two macrocycle amides forming hydrogen bonds with the competitive crystallization solvent DMF. In contrast, rotaxane 1a presented four thread–macrocycle hydrogen bonds (Figure 7 and Table 1). The strength of the hydrogen bonds could be estimated by the donor

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

• -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

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

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

• compounds, was efficiently implemented via this disulfide, which induced an aerobic oxidation. The hydroxylation and hydroxymethylation of a broad range of β-keto esters and β-keto amides that had electron-donating or -withdrawing groups on the phenyl ring gave good to excellent yields (42–98%, Scheme 10

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• N-containing functional groups on the surface of ammonia treated activated carbon samples such as bands of N–H stretching vibrations (3376–3294 cm−1), cyclic amides (1665–1641 cm−1), nitriles (2251–2265 cm−1) and pyridine-like functionalities (1334–1330 cm−1). Simultaneously, a diminished band at

• amines, imines, amides, pyridine nitrogen and pyrrole nitrogen or as oxidized nitrogen species, e.g., pyridine-N-oxides [10]. Díaz-Terán et al. examined the surface of the samples (surface groups, chemical state of the elements, metal content and distribution) during the activation process of