One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• fused imidazotetrazolodiazepinones (Scheme 2A) [37]. The Gámez-Montaño group introduced a one-pot synthesis of Ugi-azide/N-acylation/Diels–Alder/dehydration reactions for isoindolin-1-one and 1,5-DS-T in a linked manner (Scheme 2B) [41]. The Ding group developed sequential Ugi-azide/Ag-catalyzed

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• diverse dibenzodiazepinones via a copper-catalyzed C–N bond coupling between 2-halobenzoates and o-phenylenediamines leading to a key intermediate that undergoes an intramolecular N-acylation to afford the corresponding dibenzodiazepinone structure in high yields (Scheme 1b) [14]. Another innovative

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• , and aryl bromides as bromination reagents are limited. Wan and Li, respectively, demonstrated a few examples of a one-pot N-acylation and C5–H bromination of 8‑aminoquinolines using acyl bromines acting as both acyl and halide donors [25][26]. The groups of Lei and Fang independently realized the

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• developed a 2-azidobenzladehyde-based reaction sequence including a one-pot [3 + 2] cycloaddition, N-acylation and Staudinger/aza-Wittig reactions for the construction of pyrroloquinazolines and pyrrolobenzodiazepines [73]. The AcOH-catalyzed reaction of 2-azidobenzaldehydes, α-substituted amino acids and

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

• the axle, placing it away from the polymer backbone. By N-acylation of the ammonium group, a shuttling of the macrocycle towards the ester moiety is achieved, placing the chiral information of the macrocycle in closer proximity to the polymer backbone (polymers 33). The influence of the chiral BINOL

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• 26 were chosen. The reduction of the nitro groups in 24 and 26 via the hydrogenation procedure proceeded smoothly with almost quantitative yields; the amine intermediates were immediately used in the next step. Hence, the N-acylation reactions were performed by the action of the corresponding

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• requires sensitive and reactive acyl chloride derivatives. Here, we report a mild, efficient, functional group tolerant, and highly chemoselective N-acylation of indoles using thioesters as a stable acyl source. A series of indoleamides have been obtained with moderate to good yields. In addition

• , heterocycles, such as carbazole, can also be used as nucleophiles in this reaction. Keywords: indole; N-acylation; nucleophilic substitution; thioesters; Introduction Molecules containing N-acylindoles have attracted wide attention in the synthetic polymers and pharmaceutical industry because of their unique

• -acylated indoles are a widespread motif in many pharmaceuticals and natural products [6][7][8], selective N-acylation of indoles is very important. However, this process often requires unstable and reactive acyl chloride, which results in a poor functional group tolerance. Thus, developing a simple and

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• was devised for targeting specific receptors on the leukocytes membrane. The crucial N-glycosylation reaction between 1,3-oxathiolane precursor 45 and silylated cytosine was carried out using TiCl4 as a catalyst. The N-acylation of compound 92a was performed for flash chromatography, and further

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• ) [35]. During this early period, the group of Jacobsen also reported an asymmetric thiourea-catalyzed Reissert reaction of isoquinolines 21 (Scheme 5a) [36]. The mechanism proceeds by initial activation of the isoquinoline via N-acylation and subsequent dearomatization by a nucleophilic attack in the

Regioselective N-alkylation of the 1H-indazole scaffold; ring substituent and N-alkylating reagent effects on regioisomeric distribution

• Ryan M. Alam and
• John J. Keating

Beilstein J. Org. Chem. 2021, 17, 1939–1951, doi:10.3762/bjoc.17.127

• -halo carbonyl electrophiles, Hunt et al. have shown that regioselective indazole N-alkylation can be achieved through an equilibration process which favours the thermodynamic N-1 substituted product [17]. Regioselective indazole N-acylation has been suggested to provide the N-1 substituted regioisomer

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

• electrophilic activation and hydrolysis of the resulting electron-rich pyrroles in an overall N-acylation/C(7a) hydroxylation. This transformation is central to a synthesis of legonmycins A and B that requires just three laboratory operations from commercially available proline derivative 15. It is noteworthy

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• proposal features a stepwise Mannich-type reaction of the enolized anhydride 17 to the imine component and a subsequent N-acylation reaction to form the lactam target product [24]. A respective Mannich-type intermediate has been recently isolated and subsequently converted into the target lactam product

Synthesis of dihydroquinazolines from 2-aminobenzylamine: N³-aryl derivatives with electron-withdrawing groups

• Nadia Gruber,
• Jimena E. Díaz and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2018, 14, 2510–2519, doi:10.3762/bjoc.14.227

• by cyclodehydration allowed for a straightforward and efficient synthesis of 3,4-dihydroquinazolines with N-aryl substituents bearing electron-withdrawing groups. The sequence involves an initial SNAr displacement, N-acylation and MW-assisted ring closure. Remarkably, the uncatalyzed N-arylation of 2

• involving an intermediate nitrilium ion. Reaction conditions screening for the synthesis of compounds 2. Selective N-acylation of N-aryl-2-ABAs 2. Synthesis of N-aryl-3,4-dihydroquinazolines 1. Supporting Information Supporting Information File 452: Experimental procedures and characterization of new

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• hand, we finally accomplished the N-acylation reaction using n-BuLi in THF at −60 °C [15] in 60% yield. Removal of both protecting groups by catalytic hydrogenation, gave the desired compound 1 in 72% yield (Scheme 3). Compound 1 was subjected to a preliminary study to evaluate the antimicrobial

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• . Synthesis of miscellaneous spirocyclic compounds 5.1. Using stoichiometric amounts of iodine(III) reagents In 2002, Ciufolini and co-workers [123] reported the spirocyclization of various phenolic sulfonamides 122 to spiropyrrolidines 123 using PIDA (15). In this reaction, sulfonamides 122 undergo N

• -acylation, wherein various homotyramine sulfonamides were treated with electrophile PIDA (15) in hexafluoroisopropanol to give the spirocyclic products 123 in high yields (Scheme 45). However, the similar spirocyclization could not successfully applied for the construction of six-membered spiropiperidine

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• nucleoside analogues with photoreactive materials. Thus, liquid-assisted grinding of the N-hydroxysuccinimidyl esters of o-, m- or p-phenylazobenzoic acids with excess D-threoninol or of the para isomer with an aminonucleoside in the presence of DMAP and ethyl acetate engendered chemoselective N-acylation

• and carboxylic acid Boc protection using an improvised attritor-type mill. Nucleobase Boc protection via transient silylation using an improvised attritor-type mill. Chemoselective N-acylation of an aminonucleoside using LAG in a MBM. Azide–alkyne cycloaddition reactions performed in a copper vessel

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• DBU to provide a free amino group, the 2’-NH2 and 3-OH groups could be differentiated in the next acylation step by using DCC as activating agent for the N-acylation, and Steglich reaction conditions (DCC and DMAP) for the O-acylation. Following removal of the Alloc protecting group was readily

• in AcOH which reductively cleaved the N-Troc group (Scheme 3). After N-acylation by (R)-3 acyloxyacyl fatty acid and hydrolytic cleavage of 4’,6’-O-benzylidene acetal group with 90% aqueous TFA, the liberated 6’-hydroxy group was regioselectively protected as TBDMS ether to furnish 20. 1H-Tetrazole

• microfluidic conditions applied by the authors ensured even better stereoselectivity and higher yields [21]. Sequential protective group manipulation and N-acylation procedure furnished the lipid A precursor 37. The isopropylidene and anomeric allyl groups in 37 were removed and the anomeric position in 38 was

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• required functionalization of both amino groups present in 2-ABA was achieved by different routes involving selective N-acylation and cesium carbonate-mediated N-alkylation reactions, avoiding protection/deprotection steps. The heterocycles were efficiently synthesized in short reaction times by microwave

• amides 4a–c employing a THF solution of borane (yields 82–93%; see Supporting Information File 1 and Scheme 2). The synthesis of N-(2-aminobenzyl)amides 4a–k was achieved by selective N-acylation of 2-ABA or its N-substituted derivatives 3a–c, whose preparation is depicted in Scheme 2. In spite of the

• (Table 1, entries 6 and 7). Under the same reaction conditions, the N-substituted derivatives 3 (R3 ≠ H) were selectively acylated with very good yields (Table 1, entries 8–11). Thus, precursors 4 were efficiently prepared by a sequence of N-acylation–reduction–N-acylation. The acyclic precursors 5

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• ) N-acylation of the imine component followed by intramolecular Mannich reaction or (b) Mannich-type addition of the HPA enolate to a protonated imine component followed by intramolecular aminolysis of the cyclic anhydride moiety in Mannich adduct 13 (Scheme 3) [1]. Investigation of the CCR leading to

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• oligosaccharide acceptor and GDP lead to the understanding of the FUT1 mechanism [40]. Carbohydrate esterases: Carbohydrate esterases perform the de-O or de-N-acylation of carbohydrates. From a mechanistic point of view, this family of enzymes is divided into two classes, according to the dual role played by the

Derivatives of the triaminoguanidinium ion, 5. Acylation of triaminoguanidines leading to symmetrical tris(acylamino)guanidines and mesoionic 1,2,4-triazolium-3-aminides

• Jan Szabo,
• Julian Greiner and
• Gerhard Maas

Beilstein J. Org. Chem. 2017, 13, 579–588, doi:10.3762/bjoc.13.57

• -thiadiazolium-2-phenylaminides. We present now the results of our studies on the acylation of triaminoguanidines with carboxylic acid chlorides. Further, we show that N,N’,N’’-tris(benzylamino)guanidine reacts with acid chlorides to afford either the threefold N-acylation product or a mesoionic 1,2,4-triazolium

• hydrochloride (TAG-Cl) in aqueous alkaline solution, can be triply acylated to give 1,2,3-tris(acylamino)guanidinium salts only with acyl chlorides that are not easily hydrolyzed. On the other hand, 1,2,3-tris(benzylamino)guanidinium chloride underwent a threefold N-acylation under carefully controlled

• for II and III, suggesting a positively charged heteroaromatic ring system, are discontinued nowadays, because they do not represent the bond structure appropriately (vide infra). Threefold N-acylation of triaminoguanidinium chloride (1) with acyl chloride 2b. Reaction of 1,2,3-tris(benzylamino

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• corresponding β-ketoenamines 2a–e were converted into different β-ketoenamides 3a–g by N-acylation with 2-pyridinecarboxylic acid derivatives. These β-ketoenamides were treated with a mixture of TMSOTf and Hünig’s base to promote the cyclocondensation to 4-hydroxypyridine derivatives. Their immediate O

• we reported on a new pyridine synthesis starting from symmetrically substituted 1,3-diketones 1a and 1b, respectively, that were converted into the corresponding β-ketoenamines and subsequently by N-acylation into β-ketoenamides such as 3a or 3b [1]. Their cyclocondensation followed by O-alkylation

• to this compound class the design of new derivatives is possible thus supplementing the existing collection of available 2,2´-bipyridines. Results and Discussion First we prepared the corresponding β-ketoenamines 2 required for the N-acylation step (Scheme 2). The known compounds 2a and 2b are

Reactions of N,3-diarylpropiolamides with arenes under superelectrophilic activation: synthesis of 4,4-diaryl-3,4-dihydroquinolin-2(1H)-ones and their derivatives

• Larisa Yu. Gurskaya,
• Diana S. Belyanskaya,
• Dmitry S. Ryabukhin,
• Denis I. Nilov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 950–956, doi:10.3762/bjoc.12.93

• , B under the superelectrophilic activation. N-Formylation and N-acylation of dihydroquinolinones 2. Superelectrophilic activation of the N-formyl group of compounds 5 and their reaction with benzene. Reactions of amides 1a–u with benzene (and other arenes) under superelectrophilic activation, leading

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• -iodoaniline, PPTS (pyridinium p-toluenesulfonate) and NaBH4 (64%) was followed by N-acylation of the aniline nitrogen atom (80%) provided the target precursor 10. The reaction of 7 with 1 equiv of tributyltin hydride was incomplete, but the use of 2.5 equiv of tributyltin hydride at fixed concentration ([7

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• -acetylhydroxyamino acids. They were in fact the first researchers to at all investigate compounds belonging to this class of amino acid derivatives. Under the mantra «acidity favors O-acylation, while alkalinity favors N-acylation», they accomplished this feat by treatment of hydroxy-L-proline, DL-serine, DL