Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• underwent a [4 + 2] cycloaddition reaction (reaction 1 in Scheme 1) [69][70][71][72][73][74]. This metal-catalyzed one-pot reaction not only combined the advantages of a traditional Diels–Alder reaction and the recently developed multicomponent reactions, but also meets the goal of green and sustainable

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• [cyclohexane-1,3'-indoline] 3a albeit with low yields (entries 4–6 in Table 1). The spiro[cyclohexane-1,3'-indoline] 3a was clearly produced by a tri(n-butyl)phosphine-catalyzed formal [4 + 2] cycloaddition reaction. This result showed that tri(n-butyl)phosphine has a higher nucleophilic catalytic ability than

Recent advances in the tandem annulation of 1,3-enynes to functionalized pyridine and pyrrole derivatives

• Yi Liu,
• Puying Luo,
• Yang Fu,
• Tianxin Hao,
• Xuan Liu,
• Qiuping Ding and
• Yiyuan Peng

Beilstein J. Org. Chem. 2021, 17, 2462–2476, doi:10.3762/bjoc.17.163

• esterified pyridines 29 in moderate to high yield. It is worth noting that 1,3-enynes 28 bearing internal alkyne moieties were not tolerated as substrates. In 2016, Aïssa and co-workers reported a nickel-catalyzed [4 + 2]-cycloaddition of 3-azetidinones 30 with 1,3-enynes 31 for the synthesis of 3‑hydroxy

• -4,5-alkyl-substituted pyridines 33 (Scheme 11) [53]. The transformation involved a two-step sequence of successive reactions: Firstly, the nickel-catalyzed [4 + 2]-cycloaddition of 1,3-enynes 31 and N-Ts-substituted 3-azetidinone 30 afforded dihydropyridinones 32 in good yield. The next step involved

• chalcogenoamination. The derivatization of 5‑selenyl- and 5-sulfenyl-substituted nicotinates. The tandem reaction of nitriles, Reformatsky reagents, and 1,3-enynes. Nickel-catalyzed [4 + 2]-cycloaddition of 3-azetidinones with 1,3-enynes. Electrophilic iodocyclization of 2-nitro-1,3-enynes to pyrroles. Electrophilic

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• synthesized substituted anthraquinones bearing Me, Et, or hydroxy groups, such as compounds 176a–e, in moderate to good yields (45–94%) through a [4 + 2] cycloaddition reaction of 1,4-substituted naphthoquinones 174 and α,β-unsaturated aldehydes 175 catalyzed by ʟ-proline. During optimization studies, the

• -Proline-catalyzed [4 + 2] cycloaddition reaction of naphthoquinones and α,β-unsaturated aldehydes. Iridium-catalyzed [2 + 2 + 2] cycloaddition of a 1,2-bis(propiolyl)benzene derivative with alkynes. Synthesis of several anthraquinone derivatives by using InCl3 and molecular iodine. Indium-catalyzed

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• -hydroxycoumarin (1) with the chiral catalyst 48, as shown in Scheme 15 [48]. The enantioselective synthesis of dihydrocoumarins 51 from an inverse demand [4 + 2] cycloaddition of ketenes 50 with o-quinone methides 49 using carbene catalyst (NHC) 52 was described by Ye and co-workers [49].This transformation

• oxidative [4 + 2] cycloaddition with unsaturated aldehydes 57 [51]. The methodology draws attention for the wide variety of products 58 obtained with moderate to excellent yields and enantiomeric excesses (Scheme 18). Activation via noncovalent bonding Besides the activation mode via a covalent bond, as

• synthesis of 3,4-dihydrocoumarins 80 bearing a cyclohexene ring, through [4 + 2] cycloaddition between 2,4-dienals 79 and 3-coumarincarboxylates 43. This stereoselective transformation was performed using a squaramide 81 derivative catalyst, which activates the aldehyde with the formation of an enamine

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• as depicted in Scheme 56 wherein cycloketone 141 in presence of AcOH exists in equilibrium with enol form B. The imine intermediate A (condensation of aldehyde and pyrazolylamine) surrenders to a [4 + 2] cycloaddition with the enol form B and result in cycloaddition adduct C. A further dehydration

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• molecule of 5 to yield 10 and 2. Alternatively, 5 can decompose to 10 and thioacroleine (14) by a Cope elimination, which explains the formation of the heterocycles 6 and 7 by dimerization through a [4 + 2] cycloaddition [5]. Compounds 6 and 7 were also reported to be formed from 5 during gas

• chromatographic (GC) analysis by an unknown mechanism [9] (7 was confused with its double bond regioisomer 3-vinyl-3,6-dihydro-1,2-dithiine (8) in this study [5]). Under these conditions the formation of the heterocyclic disulfides 7 and 8 may not involve a dimerization of 14, as a [4 + 2] cycloaddition is not a

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

• (51.6 kJ mol−1). Whereas the entropies of activation (ΔS≠) were −181.8 and −183.1 J mol−1 K−1 for the formation of the endo and exo-isomers, respectively. The values obtained are typical for concerted [4 + 2]-cycloaddition reactions [60]. The free energies of activation () were calculated for 121.26 kJ

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

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

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• not isolated but directly converted into the norbornadienyl trifluoromethyl ketone 3 (Scheme 1). The smooth [4 + 2] cycloaddition of 1a as compared to comparably harsh thermal conditions of other propyne ketiminium salts with an internal acetylenic bond reveals the activating influence of the CF3

• phenylacetylene and DMBD or isoprene [31]. On the other hand, the 1,1-diphenylpropargyl cation was found to react with 2,4-dimethyl-1,3-pentadiene to afford a product derived from an initial [4 + 2] cycloaddition [32]. When the Diels–Alder reaction of 1a with DMBD was carried out at room temperature instead of 0

• yielding a dihydronaphthalene 16. Formally speaking, 15 results from a [2 + 2] cycloaddition and 16 from a [4 + 2] cycloaddition (Diels–Alder reaction). Under the reaction conditions, cyclobutene 15 undergoes a fast electrocyclic ring opening leading to a butadiene 17, which is finally transformed into 2

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

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

• method is also applicable for the synthesis of a wide variety of cyclopentane derivatives [12]. In 2017, Huang and co-workers reported a [4 + 2] cycloaddition reaction promoted by blue LED light, using aromatic olefins as the precursor, an acridinium photoredox catalyst (Mes–Acr–Ph+BF4−), and disulfide

• as the HAT cocatalyst, to generate the tetralin skeleton, which is widely seen in drugs and pesticide synthesis (Scheme 5) [13]. Diphenyl disulfide played an important role in the [4 + 2] cycloaddition process. Without diphenyl disulfide, only the product of the [2 + 2] cycloaddition was observed

• nonpolar solvent, PhSSPh accelerates the [4 + 2] cycloaddition of the radical cation 19, but the electron-relay catalyst promotes the [2 + 2] cycloaddition. The radical cation 19 can undergo two different types of cyclizations, subject to the relative reactivity of its radical and cation center. The α

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

• (Scheme 26) [61][67][68]. In this section, both reactions are presented and discussed. Singlet oxygen in pericyclic reactions Many important organic transformations can be performed by singlet oxygen including ene, [2 + 2] and [4 + 2] cycloaddition reactions for the formation of hydroperoxides, dioxetanes

• concerted) are still ongoing. The generally accepted mechanisms for these reactions are shown in Scheme 27, and propose a stepwise mechanism for ene and [2 + 2] cycloaddition, and a concerted mechanism for [4 + 2] cycloaddition [67]. In this part of the review, we decided to highlight the historically

Synthesis of acremines A, B and F and studies on the bisacremines

• Nils Winter and
• Dirk Trauner

Beilstein J. Org. Chem. 2019, 15, 2271–2276, doi:10.3762/bjoc.15.219

• be derived from two acremine F (5) units by a formal [4 + 2] cycloaddition followed by condensation and oxidation. Given the diversity and structural beauty of this class of natural products, it is not surprising that the acremine family has attracted the attention of the synthetic community [6][7][8

• both secondary allylic alcohols and afforded 2 in good overall yield (Scheme 3). Bisacremine E (7) was proposed to be formed in nature via [4 + 2] cycloaddition involving two acremine F (5) units [4]. Although dimerization of 5 through a Diels–Alder cycloaddition is not electronically favorable, we

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• ] cycloadditions. For the former, the reaction of an aminodiene with a triafulvene initially resulted in the formation of a [2 + 2] cycloadduct, and an energetically strained 4-membered ring inevitably undergoes subsequent ring-opening (Scheme 13a) [10]. During the [4 + 2] cycloaddition, the triafulvene could only

• the yield of the Diels–Alder adduct [227]. Of particular interest is the reaction between 6-aminofulvenes and maleic anhydride. As previously reported, a fulvene reacting with maleimides (including maleic anhydride) generally results in a [4 + 2] cycloaddition (Scheme 14, reaction pathway (i)) [55][96

• derivative [22][27]. Reaction scheme for (a) [2 + 2] cycloaddition of 1,2-diphenylmethylenecyclopropene and 1-diethylamino-1,3-butadiene and (b) [4 + 2] cycloaddition of an in situ-generated triafulvene with cyclopentadiene. Diels–Alder cycloaddition of pentafulvenes derivatives participating as dienes with

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• stepwise Pd(II)-catalyzed cascade process or a [4 + 2] cycloaddition reaction, both providing the cis stereochemistry at C-2 and C-3. When the reaction was carried out with the epimer of substrate 33 (having the 5β-hydroxy group), the cis stereochemistry was also achieved at the newly formed C-2 and C-3

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• be isolated. Finally, cyclopropyl ketone 91 would first rearrange by copper catalysis and the so-obtained furane derivative 96 would add to the carbocation in 95, followed by Friedel–Crafts cyclization, thus generating the polycyclic isoindolinones 92 in a formal hetero [4 + 2] cycloaddition process

Catalytic asymmetric oxo-Diels–Alder reactions with chiral atropisomeric biphenyl diols

• Chi-Tung Yeung,
• Wesley Ting Kwok Chan,
• Wai-Sum Lo,
• Ga-Lai Law and
• Wing-Tak Wong

Beilstein J. Org. Chem. 2019, 15, 955–962, doi:10.3762/bjoc.15.92

• stereogenic centers in a one-step [4 + 2] cycloaddition or cyclization reaction [6][7][8] and it has become hugely popular in preparing vital intermediates for the syntheses of key structural subunits of natural products with biological activities (e.g., carbohydrates, antibiotics, toxins etc.) [9][10

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

• Anne Schnell,
• J. Alexander Willms,
• S. Nozinovic and
• Marianne Engeser

Beilstein J. Org. Chem. 2019, 15, 30–43, doi:10.3762/bjoc.15.3

• formation of the enamine I seems plausible. It is an electron-rich dienophile which could undergo a [4 + 2] cycloaddition with the electron-poor aryl-substituted tetrazine 2 in a Diels–Alder reaction with inverse electron demand. The bicyclic Diels–Alder intermediate II then might undergo a retro-Diels

• contrast to the other two intermediates might indicate that the [4 + 2] cycloaddition between enamine intermediate I3 and tetrazine substrate 2 in R3 does not proceed as easily as for the untagged reaction R1 discussed above. This difference in the kinetic behavior might be due to the higher steric

• hindrance for the [4 + 2] cycloaddition with the charge-tagged enamine intermediate I3 in comparison to the untagged enamine intermediate I1. Thus, the use of the charge-tagged catalyst was essential for the detection of the elusive, but mechanistically most interesting intermediate II3. However, this comes

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• synthetic method for the direct assembly of highly functionalized tetracyclic pharmacophoric cores. Coumarins and chromones undergo diastereoselective [4 + 2] cycloaddition reactions with light-generated photoenol intermediates. The reactions occur by aid of a microfluidic photoreactor (MFP) in high yield

• anticipated that the successful development of these photoreactions would generate valuable privileged scaffolds, namely, naphthochromenones 4 and benzoxanthenes 5, through a diastereoselective light-driven [4 + 2] cycloaddition reaction. Interestingly, the tetracyclic scaffolds 4 and 5 are embodied in

• optimal reaction conditions for the light-driven [4 + 2] cycloaddition were achieved within a 1000 μL MFP with a residence time set at 35 min forming product 4a in quantitative yield, complete diastereocontrol and a productivity of 0.104 mmol·h−1 (Table 1, entry 4). On the contrary, when the same reaction

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• cycloadducts could be expected, but the 1H NMR analysis of the crude products showed that only one product was present in each case and, therefore, the studied [4 + 2] cycloaddition reactions occurred with complete regioselectivity. Based on the assumption that the nucleophilic S-atom of the thiochalcone

Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion

• Eric Detmar,
• Valentin Müller,
• Daniel Zell,
• Lutz Ackermann and
• Martin Breugst

Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130

• chemical transformations. Presumably due to attractive dispersive interactions between two adamantyl groups in the transition state of a [4 + 2] cycloaddition of benzynes (Scheme 1), the seemingly sterically more hindered product is formed preferentially [8]. Similar to other noncovalent interactions [9

[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

• 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

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• iodobiarenes to synthesize a new class of I(III) and I(V) reagents 17. These were applied for the hydroxylative dearomatization of phenolic derivatives 42 followed by the successive use of the hydroxylated products as dienes in [4 + 2] cycloaddition reactions [42]. This new reagent promoted oxygen transfer in