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

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• oxidation of 29.1 was achieved using Mes-Acr-Me+ (OD2) and a cobalt cocatalyst, ensuring an efficient dehydrogenation. Various N-heterocycles 29.3 were accessed via a radical cyclization cascade with the alkyne derivatives 29.2. Amidyl radical generation The oxidation of amides is more difficult compared to

• between the aryl substrates 30.1 and the amides 30.2 for the synthesis of the Weinreb amides 30.3 using DCA (OD5) as an organic dye. Under visible-light irradiation, the SET oxidation of 30.2 by the excited state of DCA, followed by a deprotonation, afforded the amidyl radical. This radical behaved as a

• fluorinated amides 33.3, employing the α-amido-oxy acids 33.2 and Mes-Acr-Me+ (OD2, Scheme 33) [149]. The same electrophore allowed a remote functionalization of amides to take place, as disclosed by the Leonori group [135]. 4CzIPN (OD6) was reported to be a suitable dye for the SET oxidation of such

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• absolute configuration of the Trp residue was determined using a chiral derivatizing reagent, phenylglycine methyl ester (PGME) [21]. Compound 1 was reacted with both enantiomers of PGME to give (R)- and (S)-PGME amides 5a and 5b, and the difference of the 1H NMR chemical shifts ΔδS−R was calculated around

• linear gradient of MeCN from 15% to 85% over 30 min. Retention times for the amino acid standards were 20.1 min for ʟ-Pro-ʟ-FDLA, 21.1 min for ᴅ-Pro-ʟ-FDLA, while the ʟ-FDLA-hydrolysate of 1 gave a peak at 20.1 min (Figure S8 in Supporting Information File 1). (R)- and (S)-PGME amides of 1 (5a and 5b) To

• pseudosporamicins A–C (2–4). COSY, key HMBC and ROESY correlations of pseudosporamide (1). 1H NMR ΔδS−R values for PGME amides 5a and 5b obtained from compound 1. The opposite axial chirality around the biaryl C-6–C-7'' bond influenced by the C-2 configuration in compound 1. 3D structures 1a-1 and 1b-1 are the most

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• (Te), Italy 10.3762/bjoc.16.95 Abstract Cascade cyclocarbopalladation of the readily available aryl/alkyl-substituted propargylic amides containing an aryl iodide moiety, followed by Suzuki–Miyaura coupling with arylboronic acids, allowed an efficient regio- and stereoselective synthesis of

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• the free amines gave amides 28a,b. Treatment of the latter with aqueous potassium hydroxide finally afforded (S)-2-amino-3-(2,3,4,5-tetrafluorophenyl)propionic acid (29a) and (S)-2-amino-3-(2,3,5,6-tetrafluorophenyl)propionic acid (29b) [42] (Scheme 6). Alternatively, phenylalanines 29a,b were also

Pd-catalyzed asymmetric Suzuki–Miyaura coupling reactions for the synthesis of chiral biaryl compounds with a large steric substituent at the 2-position

• Yongsu Li,
• Bendu Pan,
• Xuefeng He,
• Wang Xia,
• Yaqi Zhang,
• Hao Liang,
• Chitreddy V. Subba Reddy,
• Rihui Cao and
• Liqin Qiu

Beilstein J. Org. Chem. 2020, 16, 966–973, doi:10.3762/bjoc.16.85

• compounds can be obtained in excellent yields and good enantioselectivities under mild conditions, by using brominated amides and arylboronic acids as substrates, as well as palladium and chiral-bridged biphenyl monophosphine ligands as catalysts. Results and Discussion 2-Bromo-3-methyl-N-phenylbenzamide

• -alkyl substituted amides were found to produce better yields than N-branched alkyl chain amides, though they performed similar ee values (3a, 3b). N-Cycloalkyl-substituted amides enabled the reaction to achieve a quantitative conversion with good ee value (97% yield, 76% ee for 3c; 98% yield, 75% ee for

• 3d). The yield and ee value of an oxazolidinone amide were slightly lower than those of tetrahydropyrrolamide (3e, 3f). Various aromatic substituted amides were investigated. The results show that electron-rich or electron-deficient substituents on the phenyl ring have no significant influence on the

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• -bromo amides (Scheme 6). Many metalloporphyrins are applied as catalysts in industrial processes, such as in the oxidation of cyclohexane to cyclohexanone catalyzed by Co(II) tetraphenylporphyrin on a ton-scale [21]. Recently, Sarkar and co-workers reported the use of nickel(II) tetraphenylporphyrin

• amides (71–99% yields) and with 5–66% ee (Scheme 42). In 2018, Meng and co-workers developed a bifunctional photo-organocatalyst combining both the photosensitizer and the chirality inducer. Relevant enantiomeric excesses were observed (up to 86% ee) in the oxidation of both β-keto esters and β-keto

• amides (Scheme 43) [93]. Singlet oxygen in heteroatom oxidations Singlet oxygen reacts readily with electron pairs of heteroatoms, such as sulfur, selenium, phosphorus, and nitrogen, due to their electrophilicity. The interaction between singlet oxygen and the heteroatom occurs in both physical and

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• supported the energy transfer pathway. Thus, the proposed triplet sensitization mechanism of the photocatalytic ATRA reaction is depicted in Scheme 25. In 2016, Ji and co-workers developed a new photoredox cross-dehydrogenative coupling (CDC) method for the α-heteroarylation of amides (α to nitrogen, e.g

• ., formamide) and ethers through C–H activation using various five- and six-membered heteroarenes (e.g., benzothiazole) and employing benzaldehyde (8) as the photoinitiator [56]. This protocol was compatible with both C(sp3)–H activation (N-alkyl C–H bonds of amides or Cα–H bonds of ethers) and C(sp2)–H

• activation (carbonyl C–H bonds of formamides). Some of the amides or ethers found to be compatible with this method are shown in Scheme 26. A wide range of heteroarenes 114 was also found compatible with this method, including substituted benzothiazole substrates, substituted benzimidazoles, and thiazoles

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• , China College of Pharmacy, Jinzhou Medical University, Jinzhou, 121001, China College of Pharmacy, Jiamusi University, Jiamusi, 154007, China 10.3762/bjoc.16.73 Abstract In the present study, a practical method to prepare piperazinyl amides of 18β-glycyrrhetinic acid was developed. Two main procedures

• conditions. Furthermore, the reasons for the appearance of byproducts were elucidated. Crystallographic data of a selected piperazinyl amide is reported. Keywords: 18β-glycyrrhetinic acid; piperazinyl amides; synthesis; Introduction Glycyrrhizin was the major bioactive component in Glycyrrhiza uralensis

• amides of 18β-glycyrrhetinic acid (c) are synthesized using various methods. A method involves the C30-position of the acyl chloride with symmetric piperazine [16][17]. In this case, the acyl chloride can be prepared without purification, and the total yield over two steps can reach 81% [16]. Such