Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• synthesis [1]. Electrophilic additions of alkynes give functionalized compounds, and cycloadditions such as the Huisgen reaction afford cyclic compounds. Weakly acidic terminal alkynes can be deprotonated, and the resulting acetylides are used as carbon nucleophiles. Terminal alkynes are also used for the

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

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

• , these diazo compounds undergo [3 + 2] cycloadditions with suitable substrates to render various nitrogen-rich heterocycles [39]. In addition to their synthetic importance, these are frequently encountered as ligands in many metal complexes [40][41][42][43]. Our group have also employed 1,3-dicarbonyl

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• reaction conditions. Inverse electron-demand Diels–Alder reactions are cycloadditions between electron-rich dienophiles and electron-poor dienes. EDGs raise the electron density of dienes and, in parallel, raise the LUMOdiene–HOMOdienophile energy gap, and consequently the reactivity decreases. Although

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• discuss the primary functionalization of the fullerene core with diazo compounds to synthesize solely monosubstituted carbochain products, covers the main achievements of organic chemistry over the past 20 years in the field of [2 + 1] cycloadditions to fullerene. Review [2 + 1] Cycloaddition to C60 to

• open transannular bond (σ-homoaromatic structure) [79]. It was found that, as a rule, the [5,6]-open adducts formed initially can undergo rearrangement into [6,6]-closed isomers that are more thermodynamically stable. An alternative variant of [2 + 1] cycloadditions to the fullerene frame involves the

Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes

• Olga Bakhanovich,
• Viktor Khutorianskyi,
• Vladimir Motornov and
• Petr Beier

Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44

• , conveniently prepared by [3 + 2] cycloadditions of terminal alkynes with sulfonyl azides, have been used as the precursors to N-sulfonylindoles by transition-metal-catalyzed transannulation reactions. In the presence of Rh(II) or Ni(0) catalysts the triazole ring-opening takes place and intermediate highly

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• powerful tool for assembling a variety of fluorinated carbo- and heterocycles using either the diene [24][25][26][27][28][29][30] or the dienophile component [31][32][33][34][35][36][37][38][39] as fluorine-containing building blocks. The application of [4 + 2] cycloadditions for the preparation of

• [67] level of theory in combination with a Pople basis set and the IEFPCM [68] solvation model for o-xylene. Both functionals are already known in the literature for the investigation of cycloadditions [69][70][71][72]. For the computational details the reader is referred to Supporting Information

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

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

• -carbon quaternary centers in a single step and has been demonstrated in the synthesis of complex natural products. In this review, we present the development of all-carbon [3 + 2] cycloadditions and illustrate their application in natural product synthesis reported in the last decade covering 2011–2020

• timely and focused review of all-carbon [3 + 2] cycloadditions in natural product synthesis. In this review, we present the development of the all-carbon [3 + 2] cycloaddition and discuss its application in natural product synthesis reported from 2011–2020. We begin with describing the brief history of

• ] cycloadditions, which are usually under substrate-control. Remarkable innovation of the stereoselective palladium-catalyzed trimethylenemethane cycloaddition reported by Trost’s group, which makes use of catalytic amounts of palladium and chiral phosphine ligand 74, was applied successfully in the

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• , ring-closing, metathesis, cycloadditions, radical reactions and microwave-assisted reactions [38][39][40]. In this work, we attempt to develop a greener, simpler, more efficient and recyclable system to synthesize arylpyridine derivatives. Initially, the reaction of acetophenone (5a) and 1,3

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

• -dipolar cycloadditions under thermal or catalytic conditions [1][2]. In general, cyclic azomethine imines are classified into two types, depending on their structure: N,N'-cyclic AMIs with both nitrogen atoms included in the cyclic system and C,N-cyclic AMIs having the C=N motif in the cycle (Scheme 1) [3

• ]. A wide range of pharmaceuticals, agrochemicals, and other biologically active compounds are prepared using different types of (3 + n) cycloadditions, mainly with alkenes and alkynes [3][4][5][6][7]. For example, N,N'-cyclic azomethine imines are precursors of biologically active bicyclic

• AMIs can be generated in situ by thermal opening of any C–N bond of the diaziridine ring in 6-aryl-substituted 1,5-diazabicyclo[3.1.0]hexanes or 7-aryl-substituted 1,6-diazabicyclo[4.1.0]heptanes, respectively [16][17]. For the thermal generation conditions, the 1,3-dipolar cycloadditions of AMIs were

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• metal cavity caused overheating. Therefore, a cooling jacket around the metal cavity was implemented in the design, along with a fan to blow air through the space between the lamp and the quartz photoreactor tubes. The design was called firefly reactor. Various [2 + 2] cycloadditions were performed in

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

Regioselective cobalt(II)-catalyzed [2 + 3] cycloaddition reaction of fluoroalkylated alkynes with 2-formylphenylboronic acids: easy access to 2-fluoroalkylated indenols

• Tatsuya Kumon,
• Miroku Shimada,
• Jianyan Wu,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 2193–2200, doi:10.3762/bjoc.16.184

• [2 + 3] cycloaddition reactions with a broader substrate scope for the synthesis of fluoroalkylated indenols is still required. Herein we present a synthesis of 2-fluoroalkylated indenols via [2 + 3] cycloadditions of various fluorinated alkynes with 2-formylphenylboronic acids in the presence of

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• innovative transformations, including cycloadditions [5][6][7][8][9], intramolecular cyclizations and intermolecular addition reactions [10][11][12][13][14][15][16][17][18], as well as the use of the allenamide building block in natural product synthesis [1]. Addition reactions of allenamides, which can also

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• cycloadditions with model alkynes. Besides two ortho- and para-bromo-substituted benzaldehydes, the azide functionalization of a fluorene-based structure will be presented. The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) of the so-synthesized azide-functionalized bromocarbaldehydes with terminal

NHC-catalyzed enantioselective synthesis of β-trifluoromethyl-β-hydroxyamides

• Alyn T. Davies,
• Mark D. Greenhalgh,
• Alexandra M. Z. Slawin and
• Andrew D. Smith

Beilstein J. Org. Chem. 2020, 16, 1572–1578, doi:10.3762/bjoc.16.129

• -substituted β-lactone products in a high yield, diastereo-, and enantioselectivity (Figure 2A) [46]. Chi and co-workers have reported limited examples of oxidative [2 + 2] cycloadditions using hydrocinnamaldehyde as an azolium enolate precursor and the NHC precatalyst 2, giving β-lactone products in high

• [54]. We have previously applied these precursors in the NHC-catalyzed formal [2 + 2] cycloadditions between α-aroyloxyaldehydes and perfluoroalkyl-substituted ketones using NHC precatalyst 3 to produce polyfluorinated oxetanes and β-perfluoroalkyl-β-hydroxyamides after derivatization [55]. In this

• -hydroxyamide (Scheme 3). Conclusion In this paper, we showed that azolium enolates generated from α-aroyloxyaldehydes can undergo NHC-catalyzed formal [2 + 2] cycloadditions with trifluoroacetophenone derivatives. Although the β-lactone products proved unstable to chromatographic purification, ring opening

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

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

• cyclization, and an elimination give the desired product 27 (Scheme 7). The use of PhSSPh obviated the undesired reactions, which occurred when using Ph3SnH and Bu3SnH, respectively, as the catalyst for this reaction. Oxidation reactions Not only can disulfide catalysts induce cycloadditions of olefins but

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• + 2] cycloadditions, ring expansions and contractions, nucleophilic cyclizations, and some miscellaneous methods. The recently developed methods provide some new strategies for the efficient preparation of thietanes and their derivatives. This review focuses on the synthetic methods to construct

• , or disulfonates of alkane-1,3-diols with sodium sulfide. The intramolecular substitution of 3-mercaptoalkyl halides or sulfonates is a similar strategy for the preparation of thietanes [12][13][14]. Alternatively, inter- and intramolecular photochemical [2 + 2] cycloadditions (thia-Paternò–Büchi

• reactions) of alkenes and thiocarbonyl compounds are another important route for the synthesis of thietanes [15][16], especially, spirothietanes [17][18]. The formal [2 + 2] cycloadditions of hexafluorothioacetone and olefins are also applied in the preparation of bis(trifluoromethyl)-containing thietanes

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• diffraction crystallography of both endo 9m and exo 10m adducts (Figure 2) [43]. In addition, the thermal cycloadditions of 2-vinylpyrroles 8a–j and maleimides 7b,c took place satisfactorily to deliver the expected adducts 9e–p/10e–p, also with high endo diastereoselectivity and good yields (Table 2, entries

• 5–16). None of the series of mixtures 9a–p/10a–p corresponds to the direct products of the Diels–Alder cycloadditions, since they are derivatives resulting from the double bond isomerization of adducts 17 (i.e., migration from the pyrrole-fused exo cyclic position to the endo cyclic aromatic

• (Scheme 6). Although the reactivity was much lower (10 days) compared to the cycloadditions with 2-vinylpyrroles 8a–h (7 days) (Table 2), the diastereoselectivity remained rather high and similar to derivatives 8g and 8h. Considering the significant biological activity of indoles, octahydropyrrolo[3,4-e

[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

• systems for the control of photoreactivity. Keywords: [3 + 2] cycloadditions; β-cyclodextrin; inclusion complexes; photochemistry; phthalimides; Introduction Cycloadditions are highly useful reactions in organic synthesis providing complex cyclic structures from easily available precursors [1][2]. Among

• different reactions, [3 + 2] cycloadditions showed applicability in the synthesis of heterocyclic 5-ring compounds [3], as well as in the green synthesis of a number of natural products [4]. One of the useful synthons in [3 + 2] cycloadditions is azomethine ylide [5][6][7], also used in intramolecular

• complex molecules and natural products [11] since the pioneering work of Kanaoka et al. [12]. Photochemical reactions of phthalimides include H-abstractions, cycloadditions and photoinduced electron transfer (PET)[13]. We became interested in the application of photochemical H-abstraction reactions

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

• practical importance [1][2]. The development of chemo- and diastereoselective syntheses for these compounds is thus a challenging problem. An elegant and highly efficient method for the construction of the tetrahydrothiophene ring is based on 1,3-dipolar cycloadditions of in-situ-generated thiocarbonyl S

• by means of spectroscopic methods (R = CF3). In a recent work, an alternative, efficient and useful method for the synthesis of highly functionalized tetrahydrothiophenes of type 6 was reported [9] (Scheme 2). Under Lewis acid catalysis, formal [3 + 2]-cycloadditions of aromatic and cycloaliphatic

• the formal [4 + 3]-cycloaddition [10] (Scheme 2). In a series of our recent publications, ferrocenyl/aryl and ferrocenyl/alkyl thioketones were demonstrated to be attractive substrates for the preparation of six- and five-membered sulfur heterocycles via [4 + 2]- and [3 + 2]-cycloadditions

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

• related to natural products [18][19][20]. Among the well-established MCRs, three-component 1,3-dipolar cycloadditions of benzaldehydes, maleimides, and amino esters have been developed for making N-containing 5-membered heterocycles (Scheme 1) [21][22]. The [3 + 2] cycloadditions of maleimides with

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

• a suitable Michael acceptor 24.2 to obtain the corresponding allylation product 24.3 after a desulfonylation. Enones can also be subject to SET reductions through photoredox catalysis, and this can lead to [2 + 2] cycloadditions [2][108]. Similar intermediates can also be generated through the

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• functionalised alkyl chains at the β-position of the alkenylpyridines, the catalytic system also showed a high functional group tolerance, and thus allowing straightforward chemical transformations of the addition products, including, for example, reductions, cycloadditions, and coupling reactions (Scheme 15B