Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• on the synthesis and the coupling of three main fragments. The central fragment was synthesized via a regio-and stereoselective nitroso Diels–Alder reaction with an enol phosphate, followed by reductive cleavage of the phosphate to the ketone 11b. Coupling studies of this fragment with the lactone

• –O bond from an 1,2-oxazine, itself obtained by a nitroso Diels–Alder reaction from a chiral nitroso derivative and a functionalized diene (Figure 3). The nitroso Diels–Alder cycloaddition reaction has been well studied and has been used as a powerful tool for synthesis [19][20][21][22]. We have

• have therefore completed a quick, efficient and selective access to the central core of leustroducsins/phoslactomycins using an asymmetric nitroso Diels–Alder reaction. This fragment displays a ketone function that will be used for coupling with the lactone fragment 3 by generation of the tertiary

Enzymes in biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116

• reactions that were first known from synthetic chemistry, e.g., pericyclases can promote pericyclic reactions such as [4 + 2]-cycloaddition, also known as Diels–Alder reaction [3]. In fact, most named reactions in organic chemistry originally discovered by synthetic chemists have an analogy in nature

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• to be much more effective in the reaction than other cycloalkanes. Since the reaction is completed with a substoichiometric amount of electricity, a radical cation chain pathway is likely to be involved. Keywords: arylidene cycloalkane; Diels–Alder reaction; radical cation; single-electron transfer

• electrochemistry in most cases, probably because both single-electron oxidation and reduction are made possible at the same surface [45]. This is especially true for the radical cation Diels–Alder reaction, since non-substituted β-methylstyrene, which was previously reported as an unsuccessful dienophile, was

• found to participate under TiO2 photoelectrochemical conditions (Scheme 1) [46][47]. We questioned whether the scope of the radical cation Diels–Alder reaction could be further expanded, with particular interest on the installation of a second substituent at the β-position. Described herein is our

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

• [carbazole-2,3'-indolines], spiro[carbazole-3,5'-pyrimidines] and spiro[carbazole-3,1'-cycloalkanes] in satisfactory yields and with high diastereoselectivity. Keywords: Diels–Alder reaction; indole; indolo-2,3-quinodimethane; Levy reaction; tetrahydrocarbazole; spirooxindole; Introduction

• ][48][49][50]. On the other hand, the Diels–Alder reaction of the in situ generated indole-2,3-quinodimethanes with various dienophiles is also a powerful method for rapid construction of functionalized tetrahydrocarbazoles [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68]. In

• 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

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• ; cycloaddition; debromination; Diels−Alder reaction; mechanochemistry; Introduction The complementarity of reaction conditions [1][2][3] where the reaction takes place under some, but not under other conditions, or where a chemical reaction proceeds in a different way or mechanism is a useful feature in

• -reactions with solvent. An alternative method for the synthesis 7-oxanorbornadiene-2,3-anhydrides and imides is via retro Diels−Alder reaction employing the flash vacuum pyrolysis (FVP) technique [16]. However, the FVP also has disadvantages such as limited scope of functionalities which can withstand harsh

• . Dibromide 42 was prepared by Diels−Alder reaction of anthracene (13) and 2,3-dibromo-N-methylmaleimide (41) (Scheme 3). Heating of the reactants at 180 °C for 10 min provided the required cycloadduct 42 (98% yield). When 42 was subjected to Zn/Cu debromination in a ball mill in the presence of anthracene

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• hydrogen bonding. As a result, the Diels–Alder reaction of cyclopentadiene (128) and 127 was catalyzed. Upon addition of n-Bu4NCl, the open form was afforded that aggregated to oligomers [(126•Cl)n]n+ through intermolecular hydrogen bonding at the urea moieties. Now, activation of 127 stopped and catalysis

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

• 2002, an interesting methodology for menadione synthesis was reported by Kacan and Karabulut (Scheme 5). The authors studied a Diels–Alder reaction, using LiClO4-diethyl ether (LPDE) as a catalyst, 1-ketoxy-1,3-butadiene 28 as a diene and 2-methyl-1,4-benzoquinone (29) as dienophile. By this method

• )ruthenium(II) dichloride as catalyst. Then, a BF3·OEt2-catalzyed migration of the methyl group to the C-2 position and removal of the tert-butoxy group in a 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)/toluene mixture afforded 2-methyl-1,4-benzoquinone (29). Finally, a Diels–Alder reaction was performed with

• materials allow for the synthesis of more complex molecules such as natural products. Within this scope, the menadione (10) molecule has been explored as substrate for this versatile reaction. Ryu and co-workers described an enantioselective and structurally selective Diels–Alder reaction for the synthesis

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• ]. Conventional synthetic methods for piperidine derivatives include nucleophilic substitution (route (1) in Scheme 1), reductive amination (route (2)), intramolecular cyclization of amines and alkenes (route (3)), the Diels–Alder reaction and subsequent reduction (route (4)), and the radical cyclization reaction

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• -stoichiometric quantities of hosts because of the product inhibition effect, which arose from the entropic disadvantage of the need for binding two reactant molecules [39][40][41][42][43]. In this particular report, when the octahedral cage host A was used, the Diels–Alder reaction of 9-hydroxymethylanthracene

• employed, the site-selectivity turned back to the 1,9-position, and with catalytic turnover (Figure 1d). Only 10 mol % of B promoted the Diels–Alder reaction of 1 and N-phenylphthalimide (5) almost quantitatively affording the 9,10-adduct 6 at room temperature for 5 hours. Control experiments proved the

• molecular containers, the authors designed to investigate the Diels–Alder reaction between 2 and naphthalene 7. As expected, the reactants were encapsulated within the cage host A successfully at room temperature and formed a ternary complex A•(7•2), and after being heated at 100 °C for 8 hours, the site

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• reduction in conjugation. Another example of a tandem α-ketol rearrangement was used in the total synthesis of delitschiapyrone A (49), a cytotoxic natural product with previously demonstrated efficacy against several cancer cell lines. The final steps of the synthesis include a Diels–Alder reaction between

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• Ren-Jie Fang Chen Yan Jing Sun Ying Han Chao-Guo Yan College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.17.159 Abstract The p-TsOH-catalyzed Diels–Alder reaction of 3-(indol-3-yl)maleimides with chalcone in toluene at 60 °C afforded two

• reaction and sequential aromatization process. Keywords: carbazole; chalcone; Diels–Alder reaction; maleimide; pyrrolo[3,4-c]carbazole; 3-vinylindole; Introduction Carbazole is one of the most well-known privileged nitrogen-containing heterocycles. The carbazole skeleton is widely occurring in natural

• ][18]. Because indoles are readily available materials, the direct extension of indoles to carbazole skeletons has a great advantage [19][20][21][22][23][24][25][26][27]. Therefore, the Diels–Alder reaction of activated 2-vinylindolines or 3-vinylindolines with diverse dienophiles has become the most

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• intramolecular Diels–Alder reaction [20][25]. Compound 3 is very likely a biosynthetic precursor of 4. This is the first report on the isolation of a biosynthetic precursor of spirotetronate antibiotics as an innate metabolite from a wild-type strain, while such an intermediate was previously obtained from a

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• either onto the C=C or C=O bond. The present work should also be considered as an extension of our earlier studies focused on the exploration of 1,4-quinones in the [3 + 2]-cycloaddition and hetero-Diels–Alder reaction performed with thiocarbonyl S-methanides and thiochalcones, respectively [37][38

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• contemporarily [19][20][21]. In recent years 4-arylidenepyrrolidine-2,3-diones have been explored mainly for the preparation of bicyclic dihydropyran derivatives through the catalytic inverse-electron-demand hetero-Diels–Alder reaction [22][23][24]. We postulated that 4-arylidenepyrrolidine-2,3-diones could also

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• number of classical methodologies have been used for their synthesis, in which the key step is the generation of the six-membered ring, including the aldol reaction, the reductive amination, Mannich reaction, ring closing metathesis, Diels–Alder reaction with imines as dienophiles, aza-Prins cyclization

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

• also obtained by H-shift isomerization following the inverse electron-demand Diels–Alder reaction of tetrazines with p-quinone dibenzosuberenone. Then these pyridazines were converted to the corresponding pyrroles by reductive treatment with zinc. It was observed that all the dihydropyridazines

• cycloaddition reaction, a retro Diels–Alder reaction of the resulting adduct, and a final 1,3-prototropic hydrogen shift took place to afford cycloadducts 3a,b [55] and 3c–f (87–96% yield) (Scheme 1 and Table 1). As shown by the reaction conditions in Table 1, the reactions of tetrazine derivatives with

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• γ-lactam scaffold [40][41][42][43][44]. The pyrrolidinone fragment is often synthesized by transition metal- [45][46][47][48][49][50] or Lewis acid-catalyzed cyclization reactions [51][52][53][54]. The Diels–Alder reaction can also be used for the preparation of functionalized γ-lactams in a single

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• studies will straightforwardly focus on the enantioselective synthesis of only the (2R)-isomer. The asymmetric Ugi reaction recently developed [29] is of interest for the selective preparation of (2R)-6 (Scheme 1 and Scheme 5) [6][8]. Studies are in progress to develop an asymmetric Ugi/Diels–Alder

• reaction, and the results will be reported in due course. The in vivo inactivity of TKM-38 (3) found in this study shows the less potent neuroactivity of analogs with a larger ring C (see analogs 1–3 in Figure 1). The neuroactivity of the new analog 22, with smaller five-membered azacycle as the ring C

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

• Chemistry, Russian Academy of Sciences Leninsky prosp. 47, Moscow 119991, Russian Federation Department of Chemistry Johannes Gutenberg-University, Duesbergweg 10–14, D-55128 Mainz, Germany 10.3762/bjoc.17.27 Abstract The Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic 1,3-dienes was

• activation parameters. Furthermore, the synthetic utility of the cycloadducts obtained was demonstrated. Keywords: Diels–Alder reaction; fluorine; nitrostyrene; norbornene; stereochemistry; Introduction Organofluorine compounds play an exceptionally important role in various fields of science and

• applications [16][17][18][19][20][21], etc [22]. The use of fluorinated building blocks is a very convenient approach and in many cases represents an indispensable alternative to late-stage fluorinations in the preparation of such unique materials [23]. The Diels–Alder reaction is considered a versatile and

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• are often difficult to separate. Another drawback of this method is the difficulty of scaling, since the reaction requires strong dilution to prevent the [2π + 2π] dimerization of the starting stilbene. Among other approaches to the carbazole-based helicenes are the Diels–Alder reaction of silyl enol

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• cycloaddition (CuAAC) became very popular [16]. A variant of this, the strain-promoted alkyne–azide cycloaddition (SPAAC) even offers the possibility of in cell application, as applies also to the inverse electron-demand Diels–Alder reaction (IEDDA) [17][18]. In vitro, often a combination of orthogonal methods

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• -2,7-diyne reacted chemo- and stereoselectively in a Diels–Alder reaction with N-phenylmaleimide affording the tricyclic products as a mixture of two separable diastereoisomers, the configuration of which was estimated by DFT computations. The reported enediyne metathesis paves the way to the

• enantioselective enyne metathesis yielding chiral building blocks for compounds with potential biological activity, e.g., norsalvinorin or cacospongionolide B. Keywords: Diels–Alder reaction; enediyne; enyne metathesis; ring-closing metathesis; ruthenium precatalyst; Introduction Among the plethora of metathetic

• analogous to the methallyl group containing oxaenediynes 9, i.e., no reaction was observed for G-I catalysis and G-II or HG-II catalysis under argon, or a complex mixture was obtained for G-II or HG-II catalysis using Mori conditions (Scheme 13). Diels–Alder reaction of RCEYM product 12b In general, the

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

• coupling with TEMPO gives catalyst-bound iminium ion 261, which then cyclises with the nearby amine to produce the desired product 257 in good yields and enantioselectivities (9 examples, up to 97:3 er). Nicewicz et al. developed an enantioselective radical cation Diels–Alder reaction in both an

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• David Van Craen Jenny Begall Johannes Grosskurth Leonard Himmel Oliver Linnenberg Elisabeth Isaak Markus Albrecht Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.16.195 Abstract The stereoselectivity of a Diels–Alder reaction within the

• on the results of the stoichiometric reaction, a secondary amine-catalyzed nitro-Michael reaction is performed as well which afforded reasonable diastereoselectivities. Keywords: Diels–Alder reaction; enamine catalysis; hierarchical helicates; remote-control; stereoselectivity; Introduction Carbon

• ][17][18][19][20]. Enantioselectivities up to 25% ee at elevated temperature (32% ee at 0 °C) depending on the substrate were achieved in a Diels–Alder reaction by introducing two different substituted catechol ester ligands during the complex formation: (1) A diene-substituted ligand 1-H2 for the

Formation of an exceptionally stable ketene during phototransformations of bicyclo[2.2.2]oct-5-en-2-ones having mixed chromophores

• Asitanga Ghosh

Beilstein J. Org. Chem. 2020, 16, 2297–2303, doi:10.3762/bjoc.16.190

• groups were bulkier than the earlier reported one. Results and Discussion 5,6-Dibenzoyl-4-phenylbicyclo[2.2.2]oct-5-en-2-one (7a) and 5,6-dibenzoyl-4-isopropenylbicyclo[2.2.2]oct-5-en-2-one (7b) have been prepared through Diels–Alder reaction between substituted silyloxycyclohexa-1,3-dienes 8a and 8b [17