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

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

• group, which has both an electronic (electron-withdrawing) and steric (e.g., CF3 vs a phenyl substituent [28]) component. Moreover, a comparison with the thermal conditions of the Diels–Alder reaction of 4-phenyl-1,1,1-trifluorobut-3-yn-2-one and cyclopentadiene [29] confirms the expected accelerating

• effect of the iminium activation. The Diels–Alder reaction of alkyne 1a with 2,3-dimethylbutadiene also occurred under very mild conditions and yielded the iminium-substituted 1,4-cyclohexadiene 4-Ch (Scheme 2), which, due to its high sensitivity toward moisture, was not purified but was further

• presumably renders an ionic [2 + 2] cycloaddition pathway competitive with the Diels–Alder reaction. The few reported examples of cyclobutene formation from alkynes and unactivated 1,3-dienes include the sensitized photocycloaddition of phenylacetylene and DMBD [30] and the gold(I)-catalyzed reaction of

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• School of Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka 565-0871, Japan 10.3762/bjoc.16.150 Abstract β-Nitrostyrenes underwent a Diels–Alder reaction with Danishefsky’s diene to afford cyclohexenes together with the corresponding hydrolyzed products, 3-arylated-5-methoxy-4

• with Danishefsky’s diene could be conducted in one pot to directly afford the corresponding nitrophenols. Moreover, a heteroaryl group, e.g., a thienyl group could be introduced into the nitrophenol framework. Keywords: 3-arylated-4-nitrophenol; Danishefsky’s diene; Diels–Alder reaction; nitroalkene

• reaction, a C2 unit possessing a nitro group and an aryl group at the vicinal position is incorporated into the products. This unique reactivity prompted us to probe the synthesis of the 3-arylated-4-nitrophenols 5 by the Diels–Alder reaction of nitrostyrenes 1 with Danishefsky’s diene (2, the

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• concomitant detrifluoromethylation. Furthermore, the Lewis acid-mediated retro Diels–Alder reaction was carried out uneventfully on product 61, affording the corresponding cyclopentenone 62 in moderate yield (Scheme 33). In order to rationalize the unexpected loss of the trifluoromethyl group upon

• conjugated addition of trimethylaluminum to form 66, followed by Lewis acid-mediated retro Diels–Alder reaction (Scheme 38). In another study by Riera and co-workers, they studied the influence of the olefin counterpart on the regioselectivity of the reaction [79]. Two olefins other than norbornadiene were

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• instance, an MO picture of the SN2 reaction is attractive but less common than the compact and informative “curly arrow” picture. The Diels–Alder reaction or aromaticity, on the other hand, cannot really be treated adequately within the Lewis picture without resorting to the Dewar–Zimmerman rules [80][81

Recent synthesis of thietanes

• Jiaxi Xu

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

• 386, respectively, through another Diels–Alder reaction and an ene reaction [101] (Scheme 79). The reaction of 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (363) and quadricyclane (218) gave the bridged-thietane derivative 364 quantitatively in DMSO at 50 °C within 30 min [101] (Scheme 80). 3.3

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

• propargyl bromide (14f) to generate pyrroles 8i,j, respectively, in high yields. The synthesis of octahydropyrrolo[3,4-e]indoles 9/10 was achieved through a Diels–Alder reaction between the 2-vinylpyrroles 8a–j and 16a,b and maleimides 7a–c under thermal conditions (Scheme 3). N-Unsubstituted 2

• ]. Theoretical calculations The Diels–Alder reaction of vinylpyrroles 8b, 8c and 8g with maleimides 7b and 7c resulted in a highly diastereoselective cycloaddition leading to the mixture of endo/exo cycloadducts 9/10, where the endo product 9 was the major one (Scheme 3 and Table 2). Considering the synthetic

• out to provide additional insights into the factors controlling the endo outcome [53][82][83][84][85], documenting in some cases a key role of NCIs in the preferential stereocontrol [86]. Conclusion The Diels–Alder reaction of N-substituted-2-vinylpyrroles 8a–j and N-unsubstituted-2-vinylpyrroles 16a

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• , including the ring opening of epoxides by water and alcohols. A Diels–Alder reaction between cyclopentadiene and methyl vinyl ketone was also catalyzed by F-1 in heptane. Depending on the polarity of the solvent mixture, the CAHOF F-1 could function as a purely heterogeneous catalyst or partly dissociate

• catalyst for the Brønsted acid-catalyzed ring opening reactions of epoxides with alcohols and water, with the latter reaction occurring in a three-phase medium. In addition, a Diels–Alder reaction was promoted by F-1 in heptane. Results and Discussion Mixing together aqueous solutions of two equivalents of

• partitioning of the epoxide into the aqueous phase was necessary for reaction to occur. Cyclohexene oxide (5) is, however, a good substrate under the same reaction conditions (Table 2, entry 5), possibly due to the greater reactivity of its fused bicyclic ring system. The Diels–Alder reaction of methyl vinyl

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• Paris, Palaiseau Cedex, France 10.3762/bjoc.16.79 Abstract A diversity-oriented synthesis (DOS) approach has been used to functionalize 17-ethynyl-17-hydroxysteroids through a one-pot procedure involving a ring-closing enyne metathesis (RCEYM) and a Diels–Alder reaction on the resulting diene, under

• ) and lynestrenol (2). By using the sequence of RCEYM/Diels–Alder reaction, we rapidly synthesized "17-spirosteroid" compounds, orthogonally linking a non-steroidal polycyclic moiety to the steroid part at position 17. Spirocyclic systems play an important role in current medicinal chemistry thanks to

• Diels–Alder cycloadducts was demonstrated thanks to NOESY correlations observed between protons H-4', H-7'α at 2.30 ppm, H-8' at 3.46 ppm, and H-9' at 3.54 ppm, all on the same cyclohexene α-face. Overall, the facial selectivity of this Diels–Alder reaction seems controlled by the steric hindrance

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• et. al. [82]. The starting dienynes were obtained in a high enantiomeric purity starting form 2,6-dimethyl-1,4-benzoquinone and isoprene via an asymmetric Diels–Alder reaction. The domino metathesis reactions induced by the Grubbs second-generation catalyst proceeded in good yield (92%) thereby

• method, an enyne precursor was first converted into an exocyclic 1,3-diene in 92% yield. A Diels–Alder reaction with naphthoquinone and a deprotection step then led to the final compound (−)-zenkequinone B in a stereoselective manner (Scheme 23). C-Aryl glycosides Another interesting report from

• . Synthesis of spiro-C-aryl glycoside 24 by a tandem intramolecular enyne metathesis/Diels–Alder reaction/aromatization. Pathways to (−)-exiguolide (25) by Trost’s Ru-catalyzed enyne cross-coupling and cross-metathesis [94]. Funding Support from the Romanian Academy and from Wallonie-Bruxelles International

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• reactions and a newly developed deoxygenative aromatization procedure. The first enantioselective Diels–Alder reaction, which is an intermolecular cycloaddition and lactonization between (Z)-3-iodo-4-methylpenta-2,4-dien-1-ol (29) and methyl acrylate (30) in the presence of Mikami’s (binol)TiCl2 catalyst to

Mechanochemical Friedel–Crafts acylations

• Mateja Đud,
• Anamarija Briš,
• Iva Jušinski,
• Davor Gracin and
• Davor Margetić

Beilstein J. Org. Chem. 2019, 15, 1313–1320, doi:10.3762/bjoc.15.130

• mixture of 19 and 18 (3:2 ratio), accompanied with a small amount of 22. As a substitute for dianthracene 19, thermally more stable substrate, anthracene-N-methyl maleimide adduct 25 [54] was prepared by Diels–Alder reaction under high pressure conditions as well as by microwave-assisted reaction and

Enantioselective Diels–Alder reaction of anthracene by chiral tritylium catalysis

• Qichao Zhang,
• Jian Lv and
• Sanzhong Luo

Beilstein J. Org. Chem. 2019, 15, 1304–1312, doi:10.3762/bjoc.15.129

• of a highly active carbocation Lewis acid catalyst. The stereocontrol potential of the chiral tritylium ion pair was demonstrated by its application in an enantioselective Diels–Alder reaction of anthracene. Keywords: anthracene; carbocation catalysis; Diels–Alder reaction; Fe(III)-based phosphate

• presence of strong Lewis acids [36]. We herein report the design and exploration of a new trityl carbocation that has a chiral weakly coordinating Fe(III)-based phosphate anion for the effective asymmetric catalysis in the Diels–Alder reaction of anthracenes. Results and Discussion In our previous work, we

• ; see Supporting Information File 1 for details). We next tested the metal phosphate strategy in the Diels–Alder reaction of anthracene, for which a catalytic asymmetric version has not been achieved yet. Recently, we reported that the tritylium salt [Ph3C][BArF], in situ generated by Ph3CBr and NaBArF

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• , which allows to obtain chiral cyclic sulfones with high enantioselectivity [10][11][12]. Also non-racemic cyclic sulfones can be obtained by the Diels–Alder reaction, catalyzed by chiral Lewis acids or organocatalysts. Rh- and Cu-catalyzed CH-insertion reactions occurring at moderate or high

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

• presence of I2 as catalyst. The mechanism follows the initial formation of the imine compound between the aldehyde and the arylamine, followed by an imino-Diels–Alder reaction with the enolate generated from the ketosteroid. The reaction is highly regioselective for the enolization of the ketone, thus