Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• 1,3-dicarbonyl compounds using a catalytic amount of hydrazine hydrate without solvent in a short reaction time (10 min) [14]. Reactions of 2-aminothiophenols with β-keto esters and β-diketones under microwave irradiation (MWI) using basic alumina as heterogeneous catalyst without solvent afforded 4H

• . Results and Discussion We began our work with the condensation reactions of 2-aminothiophenols 8 and bromopyruvic acid and esters 9 to form 4H-benzo-1,4-thiazines 10, having a carboxylic acid or an ester function at the C-3 position (Scheme 1). The reaction of thiol 8a with bromo-substituted acid 9a in

• formed in 50% yield in ethanol and 30% in diethyl ether (Table 1, entries 10 and 11). Reactions with thiol 8c, having an electron-donating methoxy group, and acid 9a or esters 9b,c only gave unidentifiable decomposition products in various solvents (ethanol, diethyl ether, methanol, and CH2Cl2) at

Lewis acid-catalyzed Pudovik reaction–phospha-Brook rearrangement sequence to access phosphoric esters

• Jin Yang,
• Dang-Wei Qian and
• Shang-Dong Yang

Beilstein J. Org. Chem. 2022, 18, 1188–1194, doi:10.3762/bjoc.18.123

• previously reported base-catalyzed transformations. Keywords: Lewis acid; phospha-Brook rearrangement; phosphoric esters; Pudovik reaction; Introduction Phosphoric esters are widely used in agrochemistry, biological sciences, clinical treatments, as well as in general organic transformations [1][2][3][4][5

• ][6][7][8][9]. Therefore, many efficient methods have been developed in the past decades to synthesize different types of phosphoric esters [10][11][12][13][14][15][16][17][18]. Traditional methods for the construction of P−O bonds in phosphoric esters rely on the phosphorylation of alcohols or phenol

• with highly air-sensitive and hazardous phosphorus halides, with the assistance of a suitable base [19][20][21][22][23][24]. As an alternative pathway, the phospha-Brook rearrangement [25][26][27][28][29][30] represents a green approach to phosphoric esters since it uses α-hydroxyphosphonates, which

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• ]. Acyl or aroyl groups can be introduced into the 4-position of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones via three-component reactions of esters of acylpyruvic acid or of aroylpyruvic acid, respectively, with aromatic aldehydes, and amines. In addition, the resulting 2-pyrrolidinone derivatives also showed

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• minutes and then the corresponding alcohol was added and the reaction was stirred for two hours at room temperature. Workup and column chromatography yielded esters 3a–c and unsaturated esters 4a,b as byproducts. Good yields were obtained using benzyl and methyl alcohols (73% and 68%, respectively), while

• with the isopropyl alcohol the formation of the ester was only 37%, probably due to steric hindrance. In two cases (Table 3, entries 1 and 2) oxidation byproducts (esters 4a and 4b) were obtained, where the olefinic double bond is preserved. In contrast to the internal redox reactions of cinnamaldehyde

• giving esters 3a–c, formation of enoate byproducts 4a and 4b invoke the involvement of an external chemical oxidant species as cinnamaldehyde is added to the cathode chamber after the electrolysis has been stopped. The presence of byproducts 4a and 4b is most likely accounted for by the presence of

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• ethyl esters and diethyl chlorophosphite (83a, R = EtO) or ethyl N,N-diethylchlorophosphamidite (83b, R = NEt2) followed by an intramolecular cyclization via an intramolecular Arbuzov reaction under heating [35]. The obtained γ-phosphonolactams 85 were further hydrolyzed into 2-(3-phosphonopropyl

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• studied in detail. Computational studies For the theoretical calculations, acetyl N-(methylamino)dimethylamide model peptoids (Ac-N(NMe)n-NMe2) were used instead of the corresponding synthesized benzyl esters. The model structures were generated using the coordinates extracted from the single crystal X

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• followed by aminolysis of the obtained esters with hydroxylamine. Oxidation of the 2-methylthio group to the methylsulfonyl group and following treatment with amines resulted in the formation of the corresponding 2-amino-substituted derivatives, the ester group of which reacted with hydroxylamine to give

• of varying length and the evaluation of their HDAC inhibitory activity. Results and Discussion Chemistry Commonly, hydroxamic acids (N-hydroxyamides) are prepared by coupling activated carboxylic acids with O-protected hydroxylamine [23][24][25] or by treatment of esters with hydroxylamine [26][27

• ][28][29][30]. In this work, the pyrimidine-based hydroxamic acids were synthesized by aminolysis of the corresponding esters. The required esters 3 and 4 were obtained by alkylation of pyrimidinones 1 and 2 with ethyl 2-bromoethanoate in triethylamine in the presence of tetrabutylammonium bromide at

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• 12c in 68% isolated yield, but as tends to be the case for inactivated substrates, excess quantities of benzene (50% v/v) were required. Compounds containing esters such as methyl 3,4,5-trimethoxybenzoate and naproxen methyl ester were also tolerated and the desired products 13b and 14b were isolated

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• ][28][29][30][31]. More recently, Paradisi and co-workers disclosed a more general access to a variety of esters with mainly fruity and floral odorants by transesterification of acyl donors of structure 12 to the corresponding alcohols 11 using an immobilized transferase obtained from Mycobacterium

• esters with mainly fruity odor profiles are obtained in moderate to excellent yields. Some selected esters (14–16) and their odor profiles are shown in Scheme 4 [32]. Related methods for the esterification of natural occurring alcohols, such as geraniol, utilizing immobilized enzyme-catalysis in packed

• -bed reactors were developed by the groups of de Souza and Yadav [33][34]. Very recently, Kirschning and co-workers presented a general method for the Matteson reaction in flow, allowing iterative homologation of various terpene boronate esters 17, which are subsequently oxidized to the corresponding

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• synthetic strategy based on a procedure [21] employing the cyclization of appropriate esters of thiopyranthiones (Scheme 3). We expected that heterocyclic atom exchange used in the literature [25] for the synthesis of dithiomaltol 16b directly from commercially available maltol (14) would proceed also with

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• ) [59]. The catenane catalyst allows for the asymmetric transfer hydrogenation of 2-substituted quinolines by Hantzsch esters in a highly stereoselective fashion [60]. It was found that the catenated catalyst gives superior stereoselectivities in comparison to the macrocyclic and the acyclic reference

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• cavity could resemble the circumstance of the catalytic triad of Polyketide synthases (PKSs) [40][41][42] (Figure 1). On the other hand, the organocatalytic asymmetric decarboxylative addition reactions of MAHTs to imines provide an efficient means for accessing valuable chiral β-amino esters [43][44][45

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• ]. Examining a broad range of hydrazides in the condensation reaction with menadione, Bouhadir and co-workers reported the synthesis of various menadione acylhydrazone derivatives [126]. In this work, various acylhydrazides prepared by reaction of hydrazine hydrate with different esters were reacted with

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• derivatives may be metalated in a Li–halogen exchange reaction [27]. In another versatile approach, arylation and alkenylation reactions of the norbornadiene may be accomplished with a Suzuki–Miyaura coupling reaction. In this case, halogenated norbornadienes react with arylboronic acids or their esters to

• (HRMS). To assess the suitability of the boronic esters 2a and 2b to be used as building blocks in Suzuki–Miyaura reactions, the Pd-catalyzed cross-coupling reaction of norbornadiene 2a and bromobenzene (4a) was examined under different conditions (Table 1, Scheme 2). First experiments were conducted

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• 2021, Deng et al. showcased an unprecedented iridium-catalyzed asymmetric [4 + 3] cycloaddition of racemic 4-indolyl allylic alcohols 22 with α-imino esters 23 as azomethine ylide precursors to afford azepino[3,4,5-cd]indoles 24 in good yields and with complete regioselectivity and generally excellent

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• found viable for this transformation, giving the oxyaminated product in good yield and moderate enantioselectivity (4n). Subsequently, the scope of the transformation was investigated with various alkyl esters of malonamate (Scheme 3). In addition to the methyl ester, the reaction was found to proceed

• smoothly with ethyl, tert-butyl, and p-methoxybenzyl esters of malonamate to furnish the oxyaminated products in good yields and moderate to good enantioselectivities (4o–u). Pleasingly, the reactions carried out using m-methoxybenzyl and 3,4,5-trimethoxybenzyl esters of malonamate afforded the

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• reagent [9][10][11], and phenylsulfonyl group transfer reagent [12][13]. In the field of mechanochemistry, the usefulness of N-fluorobenzenesulfonimide has been exemplified in the asymmetric fluorination of β-keto esters (Scheme 1a) [14], and in diastereoselective fluorinations (Scheme 1b) [15], which

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• hydrochloride salt, using a protocol developed by Nudelman et al. [51]. Coupling with the protected tripeptides using TBTU occurred without epimerization [52]. The two tetrapeptide allyl esters were subjected to the peptide Claisen rearrangement, the key step of the synthesis. Subjecting allyl ester 8a to the

• inhibitors with different zinc-binding motifs. Planned syntheses of Cyl-1 derivatives. Cyl-1 derivatives via peptide Claisen rearrangement. Synthesis of tetrapeptide allyl esters 8. Synthesis and late stage modifications of Cyl derivatives. Ester enolate Claisen rearrangements of tetrapeptide allyl esters 8

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• anhydrides with the chloride leaving group replaced by the appropriate sulfonate leaving group, concerning sulfamoyl chlorides (ZZ'NSO2Cl) with Z and Z' being alkyl or aryl and concerning the solvolysis of chlorosulfate esters (alkoxy- or aryloxysulfonyl chlorides), with the structures ROSO2Cl or ArOSO2Cl

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• generation of DNA-encoded chemical libraries. Results and Discussion The synthetic strategy for the synthesis of novel functionalized 1,2-oxazole derivatives is outlined in Scheme 1. The synthetic sequence began with preparing β-keto esters 2a–h by treating N-Boc-protected cyclic amino acids 1a–h with

• Meldrum’s acid in the presence of EDC·HCl and DMAP, followed by methanolysis of the corresponding adducts [27][28][31][36][37][38]. Reaction of the resulting β-keto esters 2a–h with N,N-dimethylformamide dimethylacetal afforded cycloaminyl β-enamino ketoesters 3a–h. After isolation of compounds 3a–h from

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• esters 1 and aziridines 2 (Scheme 2). Different 2-arylaziridines 2 were reacted with diazo ester 1a, affording oxazolines 3aa–ai in 60–91% yields. No obvious electronic effect was observed. Steric bulky 2-(2-chlorophenyl)aziridine (2f) gave the desired product 3af in the highest yield of 91%. Steric 2

• diazo esters 1 and aziridine 2i were performed, generating the corresponding oxazolines 3bi–gi in 73–94% yields. Ethyl 2-diazo-3-oxohept-6-enoate showed the highest activity, affording the desired product 3gi in 94% yield. One diazo amide, 2-diazo-N,N-dimethyl-3-oxobutanamide (1h), was tested with

• heating, diazo esters 1 undergo a Wolff rearrangement to generate ethoxycarbonylketenes A by loss of nitrogen. The nucleophilic attack of 2-arylaziridine 2 on the ketene moiety produces zwitterionic intermediates B, in which the aziridinium is opened to form the benzylic carbocation stabilized through the

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• enzyme human carboxylesterase (hCE1) that cleaves carboxylic esters. This enzyme functions in the detoxification metabolism of carcinogenic and mutagenic organic compounds, converting them into nontoxic metabolites. This compound served as inspiration for Hatfield and co-workers [84], who proposed the

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• reactivity was observed for 2° and 3° alkyltrifluoroborates under the optimized conditions. The authors were able to improve the product yield by increasing the amount of TsCN and avoiding the use of additive (Scheme 18). A wide variety of functional groups such as esters, cyano, amides, ethers, ketones

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• , H3), 5.66 (t, J = 7.4 Hz, 1H, H5), 2.33 (m, 2H, H6), 3.92 (m, 1H, H7), 1.24 (d, J = 6.4 Hz, 3H, H8), 2.01 (d, J = 2.0 Hz, 3H, H9), 1.87 (s, 3H, H10). Preparation of (R)- and (S)-MPA esters 4'a–d To a solution of 4' (0.2 mg, 1.0 μmol), (R)-MPA (2.0 mg, 12 μmol), and N,N-dimethyl-4-aminopyridine (3.9

• gel thin-layer chromatography (Kieselgel 60F254; Merck Co.) developed by a mixture of CHCl3/MeOH (5:1) to give (R)-MPA esters 4'a and 4'b with a slight excess yield of the former. A recursive application of Trost’s chiral anisotropy analysis allowed to identify 4'a to be (R)-MPA ester of S- and 4'b to

• ), 1.68 (s, 3H, H10), 3.396 (s, 3H, MPA-OCH3), 4.71 (s, 1H, MPA-CαH). In the same manner as described for the preparation of 4'a and 4'b, a diastereomeric mixture of (S)-MPA esters 4'c and 4'd was prepared from 4' and (S)-MPA. (S)-MPA ester of 7S enantiomer 4'c: 1H NMR data was identical to those of 4'b

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• . Noteworthy, this methodology demonstrated a wide substrate scope, namely reacting smoothly with all-carbon backboned substrates 36c, as well as being applicable to esters and tosylamides, proving it to be a powerful protocol for the synthesis of stereocontrolled tetrasubstituted alkenes. In 2017, Sweeney and

• classically sensitive functionalities like esters and aryl chlorides. Exposure of the iron catalyst to one equivalent of aryl Grignard reagent 2b in the absence of the halide substrate afforded the bimetallic Fe(II) complex FeBr2[Mg(acac)2](THF)2. Using FeBr2[Mg(acac)2](THF)2 in place of Fe(acac)3 in the

• . Notably, the reaction did not proceed in the dark or in the absence of the photosensitizer at 30 °C; further, the reaction generated the desired product in lower yield at 120 °C. The scope was broad and tolerated a wide array of 1,3-keto esters and 1,3-diketones, as well as both benzylic and aliphatic C