Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• , alkyl N-arylideneglycinates have attracted much attention in recent years. For instance, the metal-catalyzed asymmetric [3 + 2] cycloaddition of ethyl N-benzylideneglycinates with electron-deficient alkenes has been reported to yield substituted pyrrolidines [30]. Recently, we reported the synthesis of

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

• ] developed a visible-light-induced [3 + 2] cycloaddition reaction between glycine derivatives 57 and aryl epoxides 58, which can efficiently prepare a series of multisubstituted 1,3-oxazolidines 59 at room temperature (Scheme 20). The strategy can be applied smoothly to an extensive range of glycine

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• alternative approach for the synthesis of such triazole moiety 3a is the [3 + 2] cycloaddition between alkynes and the corresponding azides. However, the major disadvantage of such a strategy is the use of 3-azidoenone which is difficult to handle owing to its explosive nature. Therefore, our method provides

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• , stereo-congested, five-membered carbocycles containing all-carbon quaternary center(s) is, at present, a distinct challenge in modern synthetic chemistry, which can be accessed through the all-carbon [3 + 2] cycloaddition. More importantly, the all-carbon [3 + 2] cycloaddition can forge vicinal all

• (inclusive). Keywords: all-carbon; cyclization; [3 + 2] cycloaddition; natural product synthesis; stereocenters; Introduction The highly-substituted, stereo-congested, five-membered carbocycle containing contiguous stereocenters is one of the most common structural features in many structurally complicated

• , the all-carbon [3 + 2] cycloaddition can forge vicinal all-carbon quaternary centers [12] in a single-step operation and provides a direct access to various substituted five-membered carbocycles. These characteristics make the all-carbon [3 + 2] cycloaddition an appealing method and/or strategy 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

• form can be explained by steric hindrance between the phenyl and the arylsulfonyl groups. Because of the observed evolution of nitrogen and sulfur in every reaction of heterocyclic thioamides and sulfonyl azides it is logic to propose the formation of a thiatriazole ring via [3 + 2] cycloaddition of

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• -Michael-type cycloadducts [28]. Very recently, a catalytic enantioselective (3 + 2) cycloaddition of diazabicyclohexanes with chalcones was carried out [30]. 1,5-Diazabicyclo[3.1.0]hexanes have been employed as precursors for 1,3-dipoles not only in (3 + 2) but also in (3 + 3) cycloadditions. It was shown

• investigated using only convection heating. The aim of the current work is to investigate the regio- and diastereoselectivity of the microwave-assisted (3 + 2) cycloaddition of 6-aryldiazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones. Results and Discussion Herein, we report the 1,3-dipolar

• cycloaddition reaction of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes 1a–d (DABCH) with 1,3-diarylpropenones 2a–l at 110 °С under microwave irradiation using a microwave oven Discover SP in a 10 mL glass reactor. It was found that under these conditions the (3 + 2) cycloaddition products – perhydropyrazolopyrazoles

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

• and enantioselectivities (12 examples, up to 97:3 er). Yoon et al. later expanded the scope of this reaction to cyclopropyl ketones 275 for the synthesis of formal [3 + 2] cycloaddition products 276 in excellent yields and enantioselectivities (21 examples, up to >99:1 er), this time using a

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

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

• of a [3 + 2] cycloaddition reactions under UV irradiation with azobis(isobutyronitrile) (AIBN) as the free radical initiator and phenyl disulfide as the catalyst, in which the three-membered rings containing double bonds and substituted olefins were transformed into five-membered-ring structures with

• used similar disulfide-catalyzed [3 + 2] cycloaddition reactions for the synthesis of polycyclic frameworks. The irradiation of vinylcyclopropanes with alkenes or alkynes in the presence of dibutyl disulfide afford the desired bi- or tricyclic products with 54–88% yield (Scheme 2) [6]. In 2014, Maruoka

• gained some interest from researchers, their full potential has not been discovered and released yet. They are environmentally friendly and efficient catalyst that deserve more attention. [3 + 2] cyclization catalyzed by diaryl disulfide. [3 + 2] cycloaddition catalyzed by disulfide. Disulfide-bridged

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• decarboxylation and [3 + 2] cycloaddition take place in the ternary complex, whereas such a reactivity from bulky adamantane 3 is less likely. This proof of principle that decarboxylation and cycloaddition can be performed in the β-CD cavity has a significant importance for the design of new supramolecular

• most probably undergoes decarboxylation delivering 1AMY from the S1 state [49]. In CH3CN, 1AMY decays with a rate constant of 2.9 × 106 M−1 s−1, and reacts with methyl acrylate in [3 + 2] cycloaddition with the rate constant 2.7 × 107 M−1 s−1 [49]. Protic solvents such as CH3OH or H2O quench

• azomethyine ylides, giving formal 1,4 H-shifted products. Thus, in the presence of H2O, no cycloaddition products are anticipated. However, it should be probed if the [3 + 2] cycloaddition can compete with the 1,4 H-shift upon irradiation of an inclusion complex. Under our conditions, photodecarboxylation of

Ferrocenyl-substituted tetrahydrothiophenes via formal [3 + 2]-cycloaddition reactions of ferrocenyl thioketones with donor–acceptor cyclopropanes

• Grzegorz Mlostoń,
• Mateusz Kowalczyk,
• André U. Augustin,
• Peter G. Jones and
• Daniel B. Werz

Beilstein J. Org. Chem. 2020, 16, 1288–1295, doi:10.3762/bjoc.16.109

• thioketones reacted with donor–acceptor cyclopropanes in dichloromethane at room temperature in the presence of catalytic amounts of Sc(OTf)3 yielding tetrahydrothiophene derivatives, products of formal [3 + 2]-cycloaddition reactions, in moderate to high yields. In all studied cases, dimethyl 2

• thioketones to form nearly equal amounts of both diastereoisomeric tetrahydrothiophenes. A low selectivity was also observed in the reaction of a 2-phthalimide-derived cyclopropane with ferrocenyl phenyl thioketone. Keywords: [3 + 2]-cycloaddition reactions; donor–acceptor cyclopropanes; ferrocenyl

• materials chemistry, and electrochemical studies [19]. In continuation of our studies on organic sulfur compounds and the mechanisms of their reactions, the main goal of the present work was the examination of the formal [3 + 2]-cycloaddition reactions of ferrocenyl-substituted thioketones 8 with D–A

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• Two kinds of [3 + 2] cycloaddition intermediates generated from the three-component reactions of 2-bromobenzaldehydes and maleimides with amino esters or amino acids were used for a one-pot N-allylation and intramolecular Heck reactions to form pyrrolidinedione-fused hexahydropyrrolo[2,1-a

• ]isoquinolines. The multicomponent reaction was combined with one-pot reactions to make a synthetic method with good pot, atom and step economy. MeCN was used as a preferable green solvent for the reactions. Keywords: [3 + 2] cycloaddition; Heck reaction; hexahydropyrrolo[2,1-a]isoquinoline; one-pot reactions

• stabilized azomethine ylides I-a generated from the condensation of aldehydes and amino esters for making pyrrolidines II-a have been well-reported [23][24][25][26], while the [3 + 2] cycloaddition of the less stable azomethine ylides I-b generated from the reaction of aldehydes and amino acids for

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

• release approach, the Xiao group reported a synthesis of the pyrroles 35.3 in 2014 [153]. They can be accessed via a photocatalytic formal [3 + 2] cycloaddition of the 2H-azirines 35.1 and the alkynes 35.2 (Scheme 35). The use of Mes-Acr-Me+ (OD2) was successful due to its high reduction potential in the

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• , the desired triazole products were generated through the [3 + 2] cycloaddition of the azide and alkyne. The recyclability analysis of these IPSi-supported Cu(I) and Cu(II) catalysts indicated seven consecutive runs with almost equivalent performances. In 2018, silica modified with a benzimidazole

• to be highly active in [3 + 2] cycloaddition reactions of halides, nonactivated terminal alkynes, and sodium azide (Scheme 21). Copper(I) ions were attached to the surface of carbon graphene as outlined in Scheme 21. Therein, GO was generated by Hummer’s method, and ascorbic acid was used to produce

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• area, reporting on the synthesis of the first heteroleptic bis-NHC and mixed NHC/phosphine copper(I) complexes [20][21][22]. Interestingly, these new copper-based complexes have shown excellent activity in the [3 + 2] cycloaddition reaction of azides/sulfonyl azides and alkynes (Scheme 1, right) [22

• diphenylamine, only 20% of the desired product was observed (12c). Interestingly, with benzyl azide, a substrate not containing a sulfonyl moiety, the product obtained is the 1,2,3-triazole derivative [33], resulting from a [3 + 2] cycloaddition of azide and alkyne (Scheme 6). The catalytic system was also

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• Analysis, Qufu 273165, P. R. China 10.3762/bjoc.15.255 Abstract A formal [3 + 2] cycloaddition between ynamides and unprotected isoxazol-5-amines has been developed in the presence of catalytic AgNTf2 in an open flask. By the protocol, a variety of functionalized 5-amino-1H-pyrrole-3-carboxamide

• use of an inexpensive catalyst, simple reaction conditions, simple work-up without column chromatographic purification for most of products and high yields. Keywords: [3 + 2] cycloaddition; isoxazole; pyrrole; silver catalysis; ynamide; Introduction Silver-catalyzed transformations of alkynes have

• employment of isoxazole nucleophiles in gold-catalyzed formal [3 + 2] cycloaddition reaction of ynamides [31][32], and zinc-catalyzed the reaction of ynol ethers [33], giving the respective multi-substituted pyrrole derivatives efficiently (Scheme 2a) [34][35]. The reaction proceeds via an α-imino gold

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• area have recently culminated in two communicated syntheses of 6,7-dideoxysqualestatin H5 (DDSQ (2), Figure 1) [12][13]. The centrepiece of both of these strategies is a rhodium(II)-catalysed tandem carbon ylide formation from a diazoketone 3 (Scheme 1) and stereoselective [3 + 2] cycloaddition with a

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• diastereoselective [3 + 2] cycloaddition reaction [14][15]. The ring expansion sequence 1 → 2 → 6 → 8 has been used as a key step in the synthesis of (±)-fragranol [16], (±)-grandisol [16], (±)-α-cuparenone [17] and (±)-herbertene [17]. Aryl cycloropyl sulfides 1 are most frequently prepared by cyclopropylation of

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• cycloaddition chemistry based on compound 1. Zheng et al. [7] first reported on the [3 + 2] cycloaddition reaction of 1 with an alkene or alkyne mediated by visible light by the aid of the photocatalyst [Ru(bpz)3](PF6)2. Our group reported the metal catalyst itself, particularly the dinuclear rhodium complex

• biomedical research [25][26][27][28][29]. Thus, based on this cycloaddition protocol, a convenient strategy can be established to synthesize trans-cyclic β-amino acids. The mechanism of the [3 + 2] cycloaddition reaction of 1a and 2a is similar to that previously reported [18] (Scheme 3). The distonic

• -centered radical B, which continues to catalyzing the reaction. Conclusion In conclusion, we report on the [3 + 2] cycloaddition reaction catalyzed by dirhodium(II) based on arylcyclopropylamine, which broadens the scope of this method to the alkynyl group. This study demonstrated that this cycloaddition

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

• Gisela V. Saborit,
• Carlos Cativiela,
• Ana I. Jiménez,
• Josep Bonjoch and
• Ben Bradshaw

Beilstein J. Org. Chem. 2018, 14, 2597–2601, doi:10.3762/bjoc.14.237

• Lycopodium alkaloids carinatine A [11][14][15], 8-deoxyserratinine [10], fawcettidine [10], fawcettimine [7][10], lycojaponicumin C [10], lycopladine A [11][13][14][15], lycoposerramine R [13][14], and sieboldine [19][20] (Figure 2). Results and Discussion Despite the potential of [3 + 2] cycloaddition

• have been used to build the hydrindane bicyclic system, but incorporating a different functionalization pattern in the cyclic compounds. Proposed here is a new methodological approach to functionalized 3a-substituted hydrindane synthesis based on a Danheiser annulation involving a [3 + 2] cycloaddition

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• numerous organic compounds [24][25][26][27][28]. The amazingly rapid and broad permeation of 1,2,3-triazoles to multidisciplinary areas can majorly be attributed to the occurrence of robust synthetic methods toward this heterocycle. The copper-catalyzed click [3 + 2] cycloaddition of azides and alkynes [29

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• the [3 + 2]-cycloaddition of electron-poor alkynes and 2H-azirines [60]. The reaction is performed under blue LED irradiation and using acridinium salts as a photocatalyst (Scheme 15). With respect to 2H-azirine the scope of the reaction is demonstrated to be relatively broad, with aromatics

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• ][1,4]diazepinium salts 10 and the related neutral, free bases 13 were synthesized from 4-acetoxy-1-acetyl-4-phenylazo-1,2,3,4-tetrahydroquinolines 8 and nitriles 9 in the presence of aluminium chloride by the [3+ + 2]-cycloaddition reaction of the in situ generated azocarbenium intermediates 14

• ][26][27][28][29][30]. Over the past years, we have been engaged in the synthesis of novel 1,2,4-triazolo heterocycles annulated to benzoazepine or heteroazepine derivatives by a tandem [3+ + 2]-cycloaddition/rearrangement between 1-aza-2-azoniaallenium ions with nitriles [31][32][33][34]. In the [3

• , we wish to describe the synthesis of unprecedented tricyclic heterocycles, i.e., 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepinium salts 10 and the related neutral free base derivatives 13 via the cationic [3+ + 2]-cycloaddition/rearrangement reactions using the bicyclic 4-acetoxy-4-azo

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• mechanism that first involves the formation of a 2’-iodobiphenyl-2-azide promoted by the copper complex. The latter then catalyzes an intermolecular [3 + 2] cycloaddition with the alkyne. Finally, the copper-triazole moiety inserts intramolecularly into the second Ar–I bond, allowing a ring closure after

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• Veronika Hladikova Jiri Vana Jiri Hanusek Institute of Organic Chemistry and Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic 10.3762/bjoc.14.113 Abstract This review covers all known examples of [3 + 2]-cycloaddition between sydnones and both terminal as well

• regioselectivity. Keywords: alkynes; Cu(I) catalysis; [3 + 2]-cycloaddition; mechanism; regioselectivity; sydnones; Review Introduction Since Huisgen’s discovery of the [3 + 2]-cycloaddition between 3-substituted sydnones and both terminal as well as internal alkynes [1][2] many researchers have tried to utilize

• bicyclic intermediate via a concerted [3 + 2]-cycloaddition followed by its very fast decomposition (extrusion of CO2) via a retro-Diels–Alder [4 + 2]-cycloaddition. The almost spontaneous extrusion of CO2 is caused by an energetically favorable aromatization occurring in this step leading to the formation