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Search for "Diels–Alder" in Full Text gives 364 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
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
- demethoxycarbonylating annulation of methyl methacrylate (33) with 3-cyanophthalide (32), in the presence of lithium tert-butoxide as catalyst (64% yield) (Scheme 7) [91]. Recently, Dissanayake and co-workers tested the stability of furans to be used as a diene in Diels–Alder reactions for the synthesis of p
Graphical Abstract
Figure 1: Natural bioactive naphthoquinones.
Figure 2: Chemical structures of vitamins K.
Figure 3: Redox cycle of menadione.
Scheme 1: Selected approaches for menadione synthesis using silver(I) as a catalyst.
Scheme 2: Methylation approaches for the preparation of menadione from 1,4-naphthoquinone using tert-butyl hy...
Scheme 3: Methylation approach of 1,4-naphthoquinone using i) rhodium complexes/methylboronic acid and ii) bi...
Scheme 4: Synthesis of menadione (10) from itaconic acid.
Scheme 5: Menadione synthesis via Diels–Alder reaction.
Scheme 6: Synthesis of menadione (10) using p-cresol as a synthetic precursor.
Scheme 7: Synthesis of menadione (10) via demethoxycarbonylating annulation of methyl methacrylate.
Scheme 8: Furan 34 used as a diene in a Diels–Alder reaction for the synthesis of menadione (10).
Scheme 9: o-Toluidine as a dienophile in a Diels–Alder reaction for the synthesis of menadione (10).
Scheme 10: Representation of electrochemical synthesis of menadione.
Figure 4: Reaction sites and reaction types of menadione as substrate.
Scheme 11: DBU-catalyzed epoxidation of menadione (10).
Scheme 12: Phase-transfer catalysis for the epoxidation of menadione.
Scheme 13: Menadione epoxidation using a hydroperoxide derived from (+)-norcamphor.
Scheme 14: Enantioselective Diels–Alder reaction for the synthesis of asymmetric quinone 50 catalyzed by a chi...
Scheme 15: Optimized reaction conditions for the synthesis of anthra[9,1-bc]pyranone.
Scheme 16: Synthesis of anthra[9,1-bc]furanone, anthra[9,1-bc]pyridine, and anthra[9,1-bc]pyrrole derivatives.
Scheme 17: Synthesis of derivatives employing protected trienes.
Scheme 18: Synthesis of cyclobutene derivatives of menadione.
Scheme 19: Menadione reduction reactions using sodium hydrosulfite.
Scheme 20: Green methodology for menadiol synthesis and pegylation.
Scheme 21: Menadione reduction by 5,6-O-isopropylidene-ʟ-ascorbic acid under UV light irradiation.
Scheme 22: Selected approaches of menadione hydroacetylation to diacetylated menadiol.
Scheme 23: Thiele–Winter reaction catalyzed by Bi(OTf)3.
Scheme 24: Carbonyl condensation of menadione using resorcinol and a hydrazone derivative.
Scheme 25: Condensation reaction of menadione with thiosemicarbazide.
Scheme 26: Condensation reaction of menadione with acylhydrazides.
Scheme 27: Menadione derivatives functionalized with organochalcogens.
Scheme 28: Synthesis of selenium-menadione conjugates derived from chloromethylated menadione 84.
Scheme 29: Menadione alkylation by the Kochi–Anderson method.
Scheme 30: Menadione alkylation by diacids.
Scheme 31: Menadione alkylation by heterocycles-substituted carboxylic acids.
Scheme 32: Menadione alkylation by bromoalkyl-substituted carboxylic acids.
Scheme 33: Menadione alkylation by complex carboxylic acids.
Scheme 34: Kochi–Anderson method variations for the menadione alkylation via oxidative decarboxylation of carb...
Scheme 35: Copper-catalyzed menadione alkylation via free radicals.
Scheme 36: Nickel-catalyzed menadione cyanoalkylation.
Scheme 37: Iron-catalyzed alkylation of menadione.
Scheme 38: Selected approaches to menadione alkylation.
Scheme 39: Menadione acylation by photo-Friedel–Crafts acylation reported by Waske and co-workers.
Scheme 40: Menadione acylation by Westwood procedure.
Scheme 41: Synthesis of 3-benzoylmenadione via metal-free TBAI/TBHP system.
Scheme 42: Michael-type addition of amines to menadione reported by Kallmayer.
Scheme 43: Synthesis of amino-menadione derivatives using polyalkylamines.
Scheme 44: Selected examples for the synthesis of different amino-substituted menadione derivatives.
Scheme 45: Selected examples of Michael-type addition of complex amines to menadione (10).
Scheme 46: Addition of different natural α-amino acids to menadione.
Scheme 47: Michael-type addition of amines to menadione using silica-supported perchloric acid.
Scheme 48: Indolylnaphthoquinone or indolylnaphthalene-1,4-diol synthesis reported by Yadav et al.
Scheme 49: Indolylnaphthoquinone synthesis reported by Tanoue and co-workers.
Scheme 50: Indolylnaphthoquinone synthesis from menadione by Escobeto-González and co-workers.
Scheme 51: Synthesis of menadione analogues functionalized with thiols.
Scheme 52: Synthesis of menadione-derived symmetrical derivatives through reaction with dithiols.
Scheme 53: Mercaptoalkyl acids as nucleophiles in Michael-type addition reaction to menadione.
Scheme 54: Reactions of menadione (10) with cysteine derivatives for the synthesis of quinoproteins.
Scheme 55: Synthesis of menadione-glutathione conjugate 152 by Michael-type addition.
Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions
- Robin Schulte and
- Heiko Ihmels
Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41
- based on Diels–Alder reactions of cyclopentadiene with alkynes [13][14][15][16][17][18][19][20][21][22][23]. However, since this synthetic route requires strongly electrophilic alkynes, its scope is limited to products that contain at least one electron-acceptor group, such as an ester, a nitrile or
Graphical Abstract
Scheme 1: Synthesis of the borylated norbornadienes 2a,b and 3.
Scheme 2: Suzuki–Miyaura coupling reactions of borono-norbornadienes 2a and 2b with selected haloarenes 4a–k.
Figure 1: Photometric monitoring of the photoisomerization of 2-(1-naphthyl)norbornadiene (5b) in MeCN, c = 2...
Scheme 3: Photo-induced, reversible conversion of the naphthylnorbornadiene 5b to quadricyclane 6b in CH3CN (...
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
Graphical Abstract
Figure 1: Piperidine and pyrrolidine rings in biologically active compounds.
Scheme 1: Conventional synthetic routes for piperidine derivatives.
Scheme 2: Synthesis of 1,2-diphenylpiperidine (3a) by the electroreductive cyclization mechanism.
Figure 2: Schematic diagram of the electroreductive cyclization for the synthesis of 1,2-diphenylpiperidine (...
Figure 3: Yield of 3a for each fraction sample in the continuous flow reductive cyclization.
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
- . Review Cycloaddition/addition Cycloaddition reactions have long been applied to molecular container-mediated enzyme-mimicking transformations [27][31][32][33], and the Fujita group has done pioneering research works in this direction [27][34]. In 2006, the authors reported unique Diels–Alder reactions of
- reports of supramolecular host-mediated Diels–Alder reactions of anthracenes, 9,10-adducts bridging the center rings of the anthracene frameworks were generally yielded [35][36][37], which resulted from the high localization of π-electron density at that sites [38]. Besides, these reactions required near
- -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
Graphical Abstract
Figure 1: Site-selective Diels–Alder reaction of anthracene and phthalimide mediated by aqueous organopalladi...
Figure 2: Site-selective Diels–Alder and [2 + 2]-photoaddition reactions between naphthalene and phthalimide ...
Figure 3: Cage host A-mediated selective 1,4-radical addition of o-quinone 10.
Figure 4: Cyclodextrin-mediated site-selective reductions.
Figure 5: Selective reduction of an α,ω-diazide compound mediated by water-soluble cavitand D.
Figure 6: Selective radical reduction of α,ω-dihalides mediated by water-soluble cavitands E and F.
Figure 7: Site-selective hydrogenation of polyenols mediated by supramolecular encapsulated rhodium catalyst.
Figure 8: Site-selective oxidation of steroids using cyclodextrin as the anchoring template.
Figure 9: Site-selective oxidations of linear diterpenoids with the help of cage host A.
Figure 10: Site-selective monoepoxidation of α,ω-dienes mediated by the water-soluble cavitand host E.
Figure 11: Site-selective ring-opening reaction of epoxides mediated by cavitand I with an inwardly directed c...
Figure 12: Site-selective nucleophilic substitution reaction of allylic chlorides mediated by cage host J.
Figure 13: Site-selective monohydrolysis of α,ω-difunctional compounds using deep water-soluble cavitands.
Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity
- Anna V. Korotina,
- Svetlana G. Tolshchina,
- Rashida I. Ishmetova,
- Natalya P. Evstigneeva,
- Natalya A. Gerasimova,
- Natalya V. Zilberberg,
- Nikolay V. Kungurov,
- Gennady L. Rusinov,
- Oleg N. Chupakhin and
- Valery N. Charushin
Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29
- labeling proteins and visualizing cancer due to the ability of s-tetrazine to fast and biocompatible ligation with alkenes via the inverse electron demand Diels–Alder reactions [29][30][31]. At the same time, azolo-annulated 1,2,4,5-tetrazines remain to be a scarcely studied class of compounds, mainly due
Graphical Abstract
Scheme 1: Chemical structures of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine (a), [1,2,4]triazolo[1,5-b][1,2,4,5...
Scheme 2: Synthesis of [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines 3a–k.
Figure 1: X-ray structure of N-(6-(4-bromo-3,5-dimethylpyrazol-1-yl)-1,2,4,5-tetrazin-3-yl)benzamide.
Scheme 3: Reactions of triazolo[1,5-b][1,2,4,5]tetrazines 3a,j with N- and O-nucleophiles.
Scheme 4: Reactions of triazolo[1,5-b][1,2,4,5]tetrazines 3a,j with C-nucleophiles.
Scheme 5: Reactions of 6-(3,5-dimethyl-1H-pyrazol-1-yl)-3-methyl-[1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine (10a...
New advances in asymmetric organocatalysis
- Radovan Šebesta
Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28
- disclosed important discoveries with proline and imidazolidinones as ample chiral catalysts for aldol [7][8], Diels–Alder [9], dipolar cycloaddition [10], and Mannich reactions [11]. The organic chemistry community this time took a tremendous interest in this concept, which led to many valuable developments
Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates
- Ekta Gupta,
- Narendra Kumar Vaishanv,
- Sandeep Kumar,
- Raja Krishnan Purshottam,
- Ruchir Kant and
- Kishor Mohanan
Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25
- noteworthy and widely explored transformations of nitrosoarenes include nitroso ene reactions [9][10][11], Diels–Alder cycloadditions [12][13][14][15][16][17][18], and nitroso aldol reactions [19][20][21][22][23]. Among the various applications of nitrosoarenes, the asymmetric nitroso aldol reaction to
Graphical Abstract
Scheme 1: Catalytic asymmetric nitroso aldol reaction.
Scheme 2: Variation of the amide moiety of malonamates. General conditions: 1 (0.20 mmol), 2a (0.24 mmol), 3a...
Figure 1: ORTEP diagram drawn with 30% ellipsoid probability for non-H atoms of the crystal structure of chir...
Scheme 3: Variation of ester moiety of malonamates and nitrosoarenes. General conditions: 1 (0.20 mmol), 2a (...
Scheme 4: Synthetic transformation.
Figure 2: Proposed transition state for the nitroso aldol reaction.
High-speed C–H chlorination of ethylene carbonate using a new photoflow setup
- Takayoshi Kasakado,
- Takahide Fukuyama,
- Tomohiro Nakagawa,
- Shinji Taguchi and
- Ilhyong Ryu
Beilstein J. Org. Chem. 2022, 18, 152–158, doi:10.3762/bjoc.18.16
- [14][15][16][17][18][19][20]. Vinylene carbonate also serves as a useful synthetic building block for Diels–Alder reactions [21][22][23][24][25] and polymerization [26][27][28][29][30]. Results and Discussion Using a PTFE tube and PTFE connectors, we connected the photoflow setup with a chlorine gas
Graphical Abstract
Scheme 1: Radical chain mechanism for a photo-induced C–H chlorination reaction.
Figure 1: Components for photoflow setup: (a) MiChS LX-1 reactor and (b) MiChS LED-s (365 ± 5 nm, 60–600 W).
Scheme 2: Model reaction: photoflow C–H chlorination of ethylene carbonate (1) to chloroethylene carbonate (2...
Figure 2: Photoflow setup for the C–H chlorination of ethylene carbonate (1).
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
- and a 22% yield of the Diels–Alder adduct, showing that the first step of the cascade had near-quantitative yield, diastereoselectively and regioselectively. The authors speculated that it is possible, considering their own reaction efficiency in conditions reminiscent of natural ones, that the
- 44 through a vinylogous α-ketol rearrangement of 45 to 46. Tandem reaction consisting of a Diels–Alder cycloaddition followed by an α-ketol rearrangement, part of the total synthesis of delitschiapyrone A (49). Single-pot reaction consisting of Claisen and α-ketol rearrangements, part of the total
Graphical Abstract
Figure 1: Generalized α-ketol or α-iminol rearrangement.
Figure 2: Nickel(II)-catalyzed enantioselective rearrangement of ketol 3 to form the ring-expanded and chiral...
Figure 3: Enantioselective ring expansion of β-hydroxy-α-dicarbonyl 6 catalyzed by a chiral copper-bisoxazoli...
Figure 4: Enantioselective rearrangement of ketols 9 and 12 and hydroxyaldimine 14 catalyzed by Al(III) or Sc...
Figure 5: Asymmetric rearrangement of α,α-dialkyl-α-siloxyaldehydes 16 to α-siloxyketones 17 catalyzed by chi...
Figure 6: BF3-promoted diastereospecific rearrangement of α-ketol 21 to difluoroalkoxyborane 22.
Figure 7: In the presence of a gold catalyst and water in 1,4-dioxane, 1-alkynylbutanol derivatives undergo t...
Figure 8: The diastereospecific α-ketol rearrangement of 32 to 33, part of the total synthesis of periconiano...
Figure 9: Two α-ketol rearrangements, one catalyzed by silica gel on 38 and the other by NaOMe on both 38 and ...
Figure 10: α-Ketol rearrangement of triumphalone (41) to isotriumphalone (42) via ring contraction.
Figure 11: Tandem reaction of strophasterol A synthetic intermediate 43 to 44 through a vinylogous α-ketol rea...
Figure 12: Tandem reaction consisting of a Diels–Alder cycloaddition followed by an α-ketol rearrangement, par...
Figure 13: Single-pot reaction consisting of Claisen and α-ketol rearrangements, part of the total synthesis o...
Figure 14: Enzyme-catalyzed α-ketol rearrangements. a) Ketol-acid reductoisomerase (KAR) catalyzes the rearran...
Figure 15: The conversion of asperfloroid (73) to asperflotone (72), featuring the ring-expanding α-ketol rear...
Figure 16: Hypothetical interconversion of natural products prekinamycin (76) and isoprekinamycin (77) and che...
Figure 17: Proposed biosynthetic pathway converting acylphloroglucinol (87) to isolated elodeoidins A–H 92–96....
Figure 18: α-Iminol rearrangements catalyzed by VANOL Zr (99). The rearrangement can be conducted with preform...
Figure 19: α-Iminol rearrangements catalyzed by silica gel and montmorillonite K 10. a) For 102a (102 with R =...
Figure 20: Synthesis of tryptamines 110 via a ring-contracting α‑iminol rearrangement. A mechanism for the fin...
Figure 21: Tandem synthesis of functionalized α-amino cyclopentanones 119 from heteroarenes 115 and cyclobutan...
Figure 22: Four eburnane-type alkaloid natural products 122–125 were synthesized from common intermediate 127,...
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
- benzylideneacetone in acetonitrile in the presence of p-TsOH and DDQ resulted in polyfunctionalized carbazoles in satisfactory yields. The reaction mechanism included the DDQ oxidative dehydrogenation of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones to the corresponding 3-vinylindoles, their acid-catalyzed Diels–Alder
- 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
Graphical Abstract
Figure 1: Representative bioactive carbazole derivatives.
Scheme 1: Synthesis of tetrahydropyrrolo[3,4-c]carbazoles 3a and 3b.
Figure 2: Single crystal structure of the isomer 3a.
Figure 3: Single crystal structure of the isomer 3b.
Figure 4: Single crystal structure of the isomer 4g.
Scheme 2: Proposed domino reaction mechanism for the formation of carbazoles 6.
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
Graphical Abstract
Figure 1: Structures of nomimicins A–D (4 and 1–3).
Figure 2: COSY and key HMBC correlations for 1.
Figure 3: Relative configuration of 1 determined by ROESY analysis.
Figure 4: Experimental ECD spectra of 1, 2, and 4 and calculated ECD spectrum of 4.
Figure 5: Four tautomers 4a–4d of the tetronic acid moiety of 4 and calculated ECD spectra.
Figure 6: COSY and key HMBC correlations for 3.
Figure 7: Relative configuration of 3 determined by NOESY analysis.
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
- 157 under reflux with concentrated HCl [69]. Synthesis of anthraquinone derivatives Friedel–Crafts intramolecular cyclization In 2013, Hilt and co-workers synthesized symmetric and asymmetric anthraquinone derivatives 162 bearing Br, Me, or OMe groups via ZnI2-catalyzed Diels–Alder reactions/DDQ
- metathesis strategy to synthesize benz[a]anthracenes. Green synthesis of oxa-aza-benzo[a]anthracene and oxa-aza-phenanthrene derivatives. Triple benzannulation of substituted naphtalene via a 1,3,6-naphthotriyne synthetic equivalent. Zinc iodide-catalyzed Diels–Alder reactions with 1,3-dienes and aroyl
Graphical Abstract
Figure 1: Examples of anthracene derivatives and their applications.
Scheme 1: Rhodium-catalyzed oxidative coupling reactions of arylboronic acids with internal alkynes.
Scheme 2: Rhodium-catalyzed oxidative benzannulation reactions of 1-adamantoyl-1-naphthylamines with internal...
Scheme 3: Gold/bismuth-catalyzed cyclization of o-alkynyldiarylmethanes.
Scheme 4: [2 + 2 + 2] Cyclotrimerization reactions with alkynes/nitriles in the presence of nickel and cobalt...
Scheme 5: Cobalt-catalyzed [2 + 2 + 2] cyclotrimerization reactions with bis(trimethylsilyl)acetylene (23).
Scheme 6: [2 + 2 + 2] Alkyne-cyclotrimerization reactions catalyzed by a CoCl2·6H2O/Zn reagent.
Scheme 7: Pd(II)-catalyzed sp3 C–H alkenylation of diphenyl carboxylic acids with acrylates.
Scheme 8: Pd(II)-catalyzed sp3 C–H arylation with o-tolualdehydes and aryl iodides.
Scheme 9: Alkylation of arenes with aromatic aldehydes in the presence of acetyl bromide and ZnBr2/SiO2.
Scheme 10: BF3·H2O-catalyzed hydroxyalkylation of arenes with aromatic dialdehyde 44.
Scheme 11: Bi(OTf)3-promoted Friedel–Crafts alkylation of triarylmethanes and aromatic acylals and of arenes a...
Scheme 12: Reduction of anthraquinones by using Zn/pyridine or Zn/NaOH reductive methods.
Scheme 13: Two-step route to novel substituted Indenoanthracenes.
Scheme 14: Synthesis of 1,8-diarylanthracenes through Suzuki–Miyaura coupling reaction in the presence of Pd-P...
Scheme 15: Synthesis of five new substituted anthracenes by using LAH as reducing agent.
Scheme 16: One-pot procedure to synthesize substituted 9,10-dicyanoanthracenes.
Scheme 17: Reduction of bromoanthraquinones with NaBH4 in alkaline medium.
Scheme 18: In(III)-catalyzed reductive-dehydration intramolecular cycloaromatization of 2-benzylic aromatic al...
Scheme 19: Acid-catalyzed cyclization of new O-protected ortho-acetal diarylmethanols.
Scheme 20: Lewis acid-mediated regioselective cyclization of asymmetric diarylmethine dipivalates and diarylme...
Scheme 21: BF3·OEt2/CF3SO3H-mediated cyclodehydration reactions of 2-(arylmethyl)benzaldehydes and 2-(arylmeth...
Scheme 22: Synthesis of 2,3,6,7-anthracenetetracarbonitrile (90) by double Wittig reaction followed by deprote...
Scheme 23: Homo-elongation protocol for the synthesis of substituted acene diesters/dinitriles.
Scheme 24: Synthesis of two new parental BN anthracenes via borylative cyclization.
Scheme 25: Synthesis of substituted anthracenes from a bifunctional organomagnesium alkoxide.
Scheme 26: Palladium-catalyzed tandem C–H activation/bis-cyclization of propargylic carbonates.
Scheme 27: Ruthenium-catalyzed C–H arylation of acetophenone derivatives with arenediboronates.
Scheme 28: Pd-catalyzed intramolecular cyclization of (Z,Z)-p-styrylstilbene derivatives.
Scheme 29: AuCl-catalyzed double cyclization of diiodoethynylterphenyl compounds.
Scheme 30: Iodonium-induced electrophilic cyclization of terphenyl derivatives.
Scheme 31: Oxidative photocyclization of 1,3-distyrylbenzene derivatives.
Scheme 32: Oxidative cyclization of 2,3-diphenylnaphthalenes.
Scheme 33: Suzuki-Miyaura/isomerization/ring closing metathesis strategy to synthesize benz[a]anthracenes.
Scheme 34: Green synthesis of oxa-aza-benzo[a]anthracene and oxa-aza-phenanthrene derivatives.
Scheme 35: Triple benzannulation of substituted naphtalene via a 1,3,6-naphthotriyne synthetic equivalent.
Scheme 36: Zinc iodide-catalyzed Diels–Alder reactions with 1,3-dienes and aroyl propiolates followed by intra...
Scheme 37: H3PO4-promoted intramolecular cyclization of substituted benzoic acids.
Scheme 38: Palladium-catalyzed intermolecular direct acylation of aromatic aldehydes and o-iodoesters.
Scheme 39: Cycloaddition/oxidative aromatization of quinone and β-enamino esters.
Scheme 40: ʟ-Proline-catalyzed [4 + 2] cycloaddition reaction of naphthoquinones and α,β-unsaturated aldehydes....
Scheme 41: Iridium-catalyzed [2 + 2 + 2] cycloaddition of a 1,2-bis(propiolyl)benzene derivative with alkynes.
Scheme 42: Synthesis of several anthraquinone derivatives by using InCl3 and molecular iodine.
Scheme 43: Indium-catalyzed multicomponent reactions employing 2-hydroxy-1,4-naphthoquinone (186), β-naphthol (...
Scheme 44: Synthesis of substituted anthraquinones catalyzed by an AlCl3/MeSO3H system.
Scheme 45: Palladium(II)-catalyzed/visible light-mediated synthesis of anthraquinones.
Scheme 46: [4 + 2] Anionic annulation reaction for the synthesis of substituted anthraquinones.
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
- , and diverse transformations are known to create new C–C bonds and/or to extend the (poly)cyclic system. In this context, cycloadditions are of special importance, and Diels–Alder reactions have successfully been explored in conversions aimed at the construction of a new, six-membered ring [5]. However
- 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
Graphical Abstract
Figure 1: Structures of exemplary benzo- and heteroaromatic fused 1,4-quinone drugs and natural products.
Scheme 1: First [3 + 2]-cycloaddition of 1,4-naphthoquinone (1a) with intermediate nitrile imine 2, generated...
Scheme 2: Selected applications of trifluoroacetonitrile imines 7 in the synthesis of S-containing 5- and 6-m...
Scheme 3: Synthesis of [3 + 2]-cycloadducts 9a–l derived from CF3-substituted nitrile imines 7a–h and 1,4-qui...
Figure 2: X-ray structure of 3-trifluoromethylpyrazole derivative 9d. The labeling scheme of the asymmetric u...
Scheme 4: Thermal elimination of MeOH from the initial [3 + 2]-cycloadduct of 1d and nitrile imine 7d generat...
Scheme 5: Formation of the thermally stable, initially formed [3 + 2]-cycloadduct 10c obtained from 1e and ni...
Figure 3: Electronic absorption spectra for selected a) naphthoquinone-derived (9c, 9d, 9g) and b) anthraquin...
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
Graphical Abstract
Scheme 1: Reactions of α-nitroketones with unsaturated pyrazolone and with 4-benzylidenepyrrolidine-2,3-dione....
Scheme 2: Reaction of 4-benzylidenedihydrofuran-2,3-dione (4) with α-nitroketones 2b,c. Reaction conditions: ...
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
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
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
Graphical Abstract
Scheme 1: General strategy for the enantioselective synthesis of N-containing heterocycles from N-tert-butane...
Scheme 2: Methodologies for condensation of aldehydes and ketones with tert-butanesulfinamides (1).
Scheme 3: Transition models for cis-aziridines and trans-aziridines.
Scheme 4: Mechanism for the reduction of N-tert-butanesulfinyl imines.
Scheme 5: Transition models for the addition of organomagnesium and organolithium compounds to N-tert-butanes...
Scheme 6: Synthesis of 2,2-dibromoaziridines 15 from aldimines 14 and bromoform, and proposed non-chelation-c...
Scheme 7: Diastereoselective synthesis of aziridines from tert-butanesulfinyl imines.
Scheme 8: Synthesis of vinylaziridines 22 from aldimines 14 and 1,3-dibromopropene 23, and proposed chelation...
Scheme 9: Synthesis of vinylaziridines 27 from aldimines 14 and α-bromoesters 26, and proposed transition sta...
Scheme 10: Synthesis of 2-chloroaziridines 28 from aldimines 14 and dichloromethane, and proposed transition s...
Scheme 11: Synthesis of cis-vinylaziridines 30 and 31 from aldimines 14 and bromomethylbutenolide 29.
Scheme 12: Synthesis of 2-chloro-2-aroylaziridines 36 and 32 from aldimines 14, arylnitriles 34, and silyldich...
Scheme 13: Synthesis of trifluoromethylaziridines 39 and proposed transition state of the aziridination.
Scheme 14: Synthesis of aziridines 42 and proposed state transition.
Scheme 15: Synthesis of 1-substituted 2-azaspiro[3.3]heptanes, 1-phenyl-2-azaspiro[3.4]octane and 1-phenyl-2-a...
Scheme 16: Synthesis of 1-substituted 2,6-diazaspiro[3.3]heptanes 48 from chiral imines 14 and 1-Boc-azetidine...
Scheme 17: Synthesis of β-lactams 52 from chiral imines 14 and dimethyl malonate (49).
Scheme 18: Synthesis of spiro-β-lactam 57 from chiral (RS)-N-tert-butanesulfinyl isatin ketimine 53 and ethyl ...
Scheme 19: Synthesis of β-lactam 60, a precursor of (−)-batzelladine D (61) and (−)-13-epi-batzelladine D (62)...
Scheme 20: Rhodium-catalyzed asymmetric synthesis of 3-substituted pyrrolidines 66 from chiral imine (RS)-63 a...
Scheme 21: Asymmetric synthesis of 1,3-disubstituted isoindolines 69 and 70 from chiral imine 67.
Scheme 22: Asymmetric synthesis of cis-2,5-disubstituted pyrrolidines 73 from chiral imine (RS)-71.
Scheme 23: Asymmetric synthesis of 3-hydroxy-5-substituted pyrrolidin-2-ones 77 from chiral imine (RS)-74.
Scheme 24: Asymmetric synthesis of 4-hydroxy-5-substituted pyrrolidin-2-ones 80 from chiral imines 79.
Scheme 25: Asymmetric synthesis of 3-pyrrolines 82 from chiral imines 14 and ethyl 4-bromocrotonate (81).
Scheme 26: Asymmetric synthesis of γ-amino esters 84, and tetramic acid derivative 86 from chiral imines (RS)-...
Scheme 27: Asymmetric synthesis of α-methylene-γ-butyrolactams 90 from chiral imines (Z,SS)-87 and ethyl 2-bro...
Scheme 28: Asymmetric synthesis of methylenepyrrolidines 92 from chiral imines (RS)-14 and 2-(trimethysilylmet...
Scheme 29: Synthesis of dibenzoazaspirodecanes from cyclic N-tert-butanesulfinyl imines.
Scheme 30: Stereoselective synthesis of cyclopenta[c]proline derivatives 103 from β,γ-unsaturated α-amino acid...
Scheme 31: Stereoselective synthesis of alkaloids (−)-angustureine (107) and (−)-cuspareine (108).
Scheme 32: Stereoselective synthesis of alkaloids (−)-pelletierine (112) and (+)-coniine (117).
Scheme 33: Synthesis of piperidine alkaloids (+)-dihydropinidine (122a), (+)-isosolenopsin (122b) and (+)-isos...
Scheme 34: Stereoselective synthesis of the alkaloids(+)-sedamine (125) from chiral imine (SS)-119.
Scheme 35: Stereoselective synthesis of trans-5-hydroxy-6-substituted-2-piperidinones 127 and 129 from chiral ...
Scheme 36: Stereoselective synthesis of trans-5-hydroxy-6-substituted ethanone-2-piperidinones 132 from chiral...
Scheme 37: Stereoselective synthesis of trans-3-benzyl-5-hydroxy-6-substituted-2-piperidinones 136 from chiral...
Scheme 38: Stereoselective synthesis of trans-5-hydroxy-6-substituted 2-piperidinones 139 from chiral imine 138...
Scheme 39: Stereoselective synthesis of ʟ-hydroxypipecolic acid 145 from chiral imine 144.
Scheme 40: Synthesis of 1-substituted isoquinolones 147, 149 and 151.
Scheme 41: Stereoselective synthesis of 3-substituted dihydrobenzo[de]isoquinolinones 154.
Scheme 42: Enantioselective synthesis of alkaloids (S)-1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (...
Scheme 43: Enantioselective synthesis of alkaloids (−)-cermizine B (171) and (+)-serratezomine E (172) develop...
Scheme 44: Stereoselective synthesis of (+)-isosolepnosin (177) and (+)-solepnosin (178) from homoallylamine d...
Scheme 45: Stereoselective synthesis of tetrahydroquinoline derivatives 184, 185 and 187 from chiral imines (RS...
Scheme 46: Stereoselective synthesis of pyridobenzofuran and pyridoindole derivatives 193 from homopropargylam...
Scheme 47: Stereoselective synthesis of 2-substituted 1,2,5,6-tetrahydropyridines 196 from chiral imines (RS)-...
Scheme 48: Stereoselective synthesis of 2-substituted trans-2,6-disubstituted piperidine 199 from chiral imine...
Scheme 49: Stereoselective synthesis of cis-2,6-disubstituted piperidines 200, and alkaloid (+)-241D, from chi...
Scheme 50: Stereoselective synthesis of 6-substituted piperidines-2,5-diones 206 and 1,7-diazaspiro[4.5]decane...
Scheme 51: Stereoselective synthesis of spirocyclic oxindoles 210 from chiral imines (RS)-53.
Scheme 52: Stereoselective synthesis of azaspiro compound 213 from chiral imine 211.
Scheme 53: Stereoselective synthesis of tetrahydroisoquinoline derivatives from chiral imines (RS)-214.
Scheme 54: Stereoselective synthesis of (−)-crispine A 223 from chiral imine (RS)-214.
Scheme 55: Synthesis of (−)-harmicine (228) using tert-butanesulfinamide through haloamide cyclization.
Scheme 56: Stereoselective synthesis of tetraponerines T1–T8.
Scheme 57: Stereoselective synthesis of phenanthroindolizidines 246a and (−)-tylophorine (246b), and phenanthr...
Scheme 58: Stereoselective synthesis of indoline, tetrahydroquinoline and tetrahydrobenzazepine derivatives 253...
Scheme 59: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldimine (RS)-79.
Scheme 60: Stereoselective synthesis of (−)-epiquinamide (266) from chiral aldimine (SS)-261.
Scheme 61: Synthesis synthesis of (–)-hippodamine (273) and (+)-epi-hippodamine (272) using chiral sulfinyl am...
Scheme 62: Stereoselective synthesis of (+)-grandisine D (279) and (+)-amabiline (283).
Scheme 63: Stereoselective synthesis of (−)-epiquinamide (266) and (+)-swaisonine (291) from aldimine (SS)-126....
Scheme 64: Stereoselective synthesis of (+)-C(9a)-epi-epiquinamide (294).
Scheme 65: Stereoselective synthesis of (+)-lasubine II (298) from chiral aldimine (SS)-109.
Scheme 66: Stereoselective synthesis of (−)-epimyrtine (300a) and (−)-lasubine II (ent-302) from β-amino keton...
Scheme 67: Stereoselective synthesis of (−)-tabersonine (310), (−)-vincadifformine (311), and (−)-aspidospermi...
Scheme 68: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldehyde 313 and ...
Scheme 69: Total synthesis of (+)-lysergic acid (323) from N-tert-butanesulfinamide (RS)-1.
Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years
- Asha Budakoti,
- Pradip Kumar Mondal,
- Prachi Verma and
- Jagadish Khamrai
Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77
- products [1][2][3][4][5][6][7][8]. Prins and related cyclization reactions [9][10], hetero-Diels–Alder cyclization [11], cyclization onto epoxides [12], Petasis–Ferrier rearrangement [13], intramolecular oxa-Michael reactions [14], cyclization through oxidative C–H bond functionalization [15], ring-closing
Graphical Abstract
Scheme 1: General strategy for the synthesis of THPs.
Scheme 2: Developments towards the Prins cyclization.
Scheme 3: General stereochemical outcome of the Prins cyclization.
Scheme 4: Regioselectivity in the Prins cyclization.
Scheme 5: Mechanism of the oxonia-Cope reaction in the Prins cyclization.
Scheme 6: Cyclization of electron-deficient enantioenriched alcohol 27.
Scheme 7: Partial racemization through 2-oxonia-Cope allyl transfer.
Scheme 8: Partial racemization by reversible 2-oxonia-Cope rearrangement.
Scheme 9: Rychnovsky modification of the Prins cyclization.
Scheme 10: Synthesis of (−)-centrolobine and the C22–C26 unit of phorboxazole A.
Scheme 11: Axially selective Prins cyclization by Rychnovsky et al.
Scheme 12: Mechanism for the axially selectivity Prins cyclization.
Scheme 13: Mukaiyama aldol–Prins cyclization reaction.
Scheme 14: Application of the aldol–Prins reaction.
Scheme 15: Hart and Bennet's acid-promoted Prins cyclization.
Scheme 16: Tetrahydropyran core of polycarvernoside A as well as (−)-clavoslide A and D.
Scheme 17: Scheidt and co-workers’ route to tetrahydropyran-4-one.
Scheme 18: Mechanism for the Lewis acid-catalyzed synthesis of tetrahydropyran-4-one.
Scheme 19: Hoveyda and co-workers’ strategy for 2,6-disubstituted 4-methylenetetrahydropyran.
Scheme 20: Funk and Cossey’s ene-carbamates strategy.
Scheme 21: Yadav and Kumar’s cyclopropane strategy for THP synthesis.
Scheme 22: 2-Arylcylopropylmethanolin in centrolobine synthesis.
Scheme 23: Yadav and co-workers’ strategy for the synthesis of THP.
Scheme 24: Yadav and co-workers’ Prins–Ritter reaction sequence for 4-amidotetrahydropyran.
Scheme 25: Yadav and co-workers’ strategy to prelactones B, C, and V.
Scheme 26: Yadav and co-workers’ strategy for the synthesis of (±)-centrolobine.
Scheme 27: Loh and co-workers’ strategy for the synthesis of zampanolide and dactylolide.
Scheme 28: Loh and Chan’s strategy for THP synthesis.
Scheme 29: Prins cyclization of cyclohexanecarboxaldehyde.
Scheme 30: Prins cyclization of methyl ricinoleate (127) and benzaldehyde (88).
Scheme 31: AlCl3-catalyzed cyclization of homoallylic alcohol 129 and aldehyde 130.
Scheme 32: Martín and co-workers’ stereoselective approach for the synthesis of highly substituted tetrahydrop...
Scheme 33: Ene-IMSC strategy by Marko and Leroy for the synthesis of tetrahydropyran.
Scheme 34: Marko and Leroy’s strategy for the synthesis of tetrahydropyrans 146.
Scheme 35: Sakurai dimerization/macrolactonization reaction for the synthesis of cyanolide A.
Scheme 36: Hoye and Hu’s synthesis of (−)-dactyloide by intramolecular Sakurai cyclization.
Scheme 37: Minehan and co-workers’ strategy for the synthesis of THPs 157.
Scheme 38: Yu and co-workers’ allylic transfer strategy for the construction of tetrahydropyran 161.
Scheme 39: Reactivity enhancement in intramolecular Prins cyclization.
Scheme 40: Floreancig and co-workers’ Prins cyclization strategy to (+)-dactyloide.
Scheme 41: Panek and Huang’s DHP synthesis from crotylsilanes: a general strategy.
Scheme 42: Panek and Huang’s DHP synthesis from syn-crotylsilanes.
Scheme 43: Panek and Huang’s DHP synthesis from anti-crotylsilanes.
Scheme 44: Roush and co-workers’ [4 + 2]-annulation strategy for DHP synthesis [82].
Scheme 45: TMSOTf-promoted annulation reaction.
Scheme 46: Dobb and co-workers’ synthesis of DHP.
Scheme 47: BiBr3-promoted tandem silyl-Prins reaction by Hinkle et al.
Scheme 48: Substrate scope of Hinkle and co-workers’ strategy.
Scheme 49: Cho and co-workers’ strategy for 2,6 disubstituted 3,4-dimethylene-THP.
Scheme 50: Furman and co-workers’ THP synthesis from propargylsilane.
Scheme 51: THP synthesis from silyl enol ethers.
Scheme 52: Rychnovsky and co-workers’ strategy for THP synthesis from hydroxy-substituted silyl enol ethers.
Scheme 53: Li and co-workers’ germinal bissilyl Prins cyclization strategy to (−)-exiguolide.
Scheme 54: Xu and co-workers’ hydroiodination strategy for THP.
Scheme 55: Wang and co-workers’ strategy for tetrahydropyran synthesis.
Scheme 56: FeCl3-catalyzed synthesis of DHP from alkynylsilane alcohol.
Scheme 57: Martín, Padrón, and co-workers’ proposed mechanism of alkynylsilane Prins cyclization for the synth...
Scheme 58: Marko and co-workers’ synthesis of 2,6-anti-configured tetrahydropyran.
Scheme 59: Loh and co-workers’ strategy for 2,6-syn-tetrahydropyrans.
Scheme 60: Loh and co-workers’ strategy for anti-THP synthesis.
Scheme 61: Cha and co-workers’ strategy for trans-2,6-tetrahydropyran.
Scheme 62: Mechanism proposed by Cha et al.
Scheme 63: TiCl4-mediated cyclization to trans-THP.
Scheme 64: Feng and co-workers’ FeCl3-catalyzed Prins cyclization strategy to 4-hydroxy-substituted THP.
Scheme 65: Selectivity profile of the Prins cyclization under participation of an iron ligand.
Scheme 66: Sequential reactions involving Prins cyclization.
Scheme 67: Banerjee and co-workers’ strategy of Prins cyclization from cyclopropane carbaldehydes and propargy...
Scheme 68: Mullen and Gagné's (R)-[(tolBINAP)Pt(NC6F5)2][SbF6]2-catalyzed asymmetric Prins cyclization strateg...
Scheme 69: Yu and co-workers’ DDQ-catalyzed asymmetric Prins cyclization strategy to trisubstituted THPs.
Scheme 70: Lalli and Weghe’s chiral-Brønsted-acid- and achiral-Lewis-acid-promoted asymmetric Prins cyclizatio...
Scheme 71: List and co-workers’ iIDP Brønsted acid-promoted asymmetric Prins cyclization strategy.
Scheme 72: Zhou and co-workers’ strategy for chiral phosphoric acid (CPA)-catalyzed cascade Prins cyclization.
Scheme 73: List and co-workers’ approach for asymmetric Prins cyclization using chiral imidodiphosphoric acid ...
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
- inverse electron-demand Diels–Alder cycloaddition reactions between a dibenzosuberenone and tetrazines that bear various substituents. The pyridazines were synthesized in high yields by oxidation of dihydropyridazine-appended dibenzosuberenones with PIFA or NO. p-Quinone derivatives of pyridazines were
- 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
- obtained gave absorbance and emission at long wavelengths. Keywords: dibenzosuberenone; inverse electron-demand Diels–Alder cycloaddition reactions; p-quinone methide; polycyclic π-conjugated dihydropyridazines; pyridazines; pyrroles; Inroduction Dibenzosuberone and dibenzosuberenone derivatives are
Graphical Abstract
Figure 1: Structures of dibenzosuberenone 1 and pyridazine and pyrrole derivatives.
Figure 2: Structures of s-tetrazines 2a–l.
Scheme 1: Inverse electron-demand Diels–Alder reactions of dibenzosuberenone (1) with tetrazines 2a–l.
Scheme 2: Inverse electron-demand Diels–Alder reactions between dibenzosuberenone 1 and tetrazines 2ka and 2lb...
Scheme 3: Proposed reaction mechanism for the formation of dibenzosuberenone derivatives 3 and 4.
Scheme 4: Proposed mechanism for the formation of 5l.
Scheme 5: Oxidation of dihydropyridazines 3a–f. All reactions were carried in CH2Cl2 at room temperature (4e:...
Scheme 6: Synthesis of pyrrole 10a. a1.34 mmol 4a, Zinc (for 10aa: 6.68 mmol, for 10ab: 13.36 mmol), 10 mL gl...
Scheme 7: Synthesis of pyrrole 10b. a1.21 mmol 4b, 12.10 mmol Zinc, 118 °C, 2 h. b1.13 mmol 10ba, 1.69 mmol K...
Scheme 8: Synthesis of p-quinone methides 13–16. a1.77 mmol 11, 1.77 mmol 2, 5 mL toluene, 80 °C (13a: overni...
Scheme 9: Proposed mechanism for the formation of 13.
Figure 3: UV–vis spectra of 3c–f and 3k in CH3CN at rt (c = 5 μM).
Figure 4: Fluorescence spectra of 3c–f and 3k in CH3CN at rt (c = 5 μM).
Figure 5: Ambient (top) and fluorescence (bottom, under 365 nm UV light) images of 3c–f and 3k in CH3CN.
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
Graphical Abstract
Figure 1: Selected alkaloids containing the pyrrolidone motif.
Scheme 1: A) Classical γ-lactam synthesis by atom transfer radical cyclizations; B) previously developed tand...
Figure 2: X-ray crystal structure of the major (2R,4S)-alkoxyamine hydrochloride derived from 9j. Displacemen...
Scheme 2: Formation of the α-(aminoxy)amides 9o,p.
Figure 3: X-ray crystal structure of the minor cis-diastereomers of the keto lactam 13j (left) and the hydrox...
Scheme 3: Thermal radical cyclization reactions of amides 9l–p bearing cyclic units. Conditions: a) t-BuOH, 1...
Scheme 4: Epimerization of spirolactams 12m,n.
Scheme 5: The Dess–Martin oxidation of lactams 12l–o. Conditions: a) DMP (1.3 equiv), t-BuOH (10 mol %), CH2Cl...
Scheme 6: Selected transformations of the lactams trans-12b and 12o.
Scheme 7: Diastereoselectivity for the formation of α-(aminoxy)amides 9i–k.
Scheme 8: Rationalization of the diastereoselectivity for the formation of the α-(aminoxy)amide 9l.
Scheme 9: Rationalization of the thermal radical cyclization diastereoselectivity of alkoxyamines 9a–k. (S)-C...
Scheme 10: The stereochemical course for the formation of products 12m,n by thermal radical cyclization of alk...
Scheme 11: Formation of bicycles 12o,p.
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
Graphical Abstract
Figure 1: Artificial glutamate analogs synthesized in an enantiomerically pure form.
Scheme 1: Our established synthetic route to racemic MC-27 ((rac)-4) [5-7].
Scheme 2: Resolution of the MC-27 precursor (rac)-7 by a chiral auxiliary.
Figure 2: Chiral chromatography profiles for the separation of menthyl ester diastereomers 9 and 9*. Conditio...
Scheme 3: Final elaboration of (2R)-MC-27 (4).
Figure 3: Superimposed structures of the top 3 stable conformers (76.5% total population) generated by CONFLE...
Figure 4: Crystallographic analysis of the menthyl ester 10, unequivocally showing the 2R configuration (CCDC...
Scheme 4: Synthesis of (2S)-MC-27 (4*) from 9*.
Scheme 5: Construction and chiral resolution of the 5/5/8-ring system towards the TKM-38 enantiomers.
Figure 5: Structure of Zhan catalyst-1B (14) [14].
Figure 6: Chiral HPLC profiles for the separation of menthyl ester diastereomers 20* and 20. Conditions: 4.6 ...
Scheme 6: Final elaboration towards (2R)- and (2S)-TKM-38.
Figure 7: Superimposed structures of the top 5 stable conformers (89.9% total population) generated by CONFLE...
Figure 8: Superimposed structures of the top 5 stable conformers (76.8% total population) generated by CONFLE...
Figure 9: Key interactions that are supposed to control the spatial arrangement of the heterotricycle and the...
Figure 10: The future synthetic target 22 is expected to show potent neuroactivity.
Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF3)2CHOH]
- Takeshi Fujita,
- Noriaki Shoji,
- Nao Yoshikawa and
- Junji Ichikawa
Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35
- reactions (Scheme 1a). Diels–Alder (Scheme 1b) [15] and radical reactions (Scheme 1c) [16] directed toward helicene synthesis require high temperature conditions even for low to moderate yields. Olefin metathesis (Scheme 1d) [17] and alkyne trimerization (Scheme 1e) [18][19] require the use of expensive
Graphical Abstract
Scheme 1: Conventional methods for the synthesis of helicenes.
Scheme 2: Brønsted acid-catalyzed cycloaromatization of biaryls bearing an acetal moiety.
Scheme 3: Two strategies for the helicene synthesis via Suzuki–Miyaura coupling/cycloaromatization sequence.
Scheme 4: Synthesis of (a) [5]helicene and (b) [6]helicene.
Scheme 5: Synthesis of helicenes with double helical structures.
Scheme 6: Synthesis of hetero[4]-, [5]-, and [6]helicenes.
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
Graphical Abstract
Scheme 1: Scope of the nitrostyrenes 1 in the Diels–Alder reaction with CPD (dr = exo:endo).
Figure 1: The structure assignment of norbornenes 2 by 1H (a) and NOE (b) NMR spectroscopy.
Figure 2: 13C NMR spectrum of the mixture of exo- and endo-isomers of norbornene 2l.
Figure 3: The predicted reaction pathway for the Diels–Alder reaction of nitrostyrene 1h with CPD is displaye...
Scheme 2: The Diels–Alder reaction of nitrostyrene 1h with spiro[2.4]hepta-4,6-diene.
Scheme 3: Diels–Alder reaction of nitrostyrenes 1 with CHD (dr = exo:endo). (а) Reaction under microwave acti...
Scheme 4: Kinetic study of reactions of 1h with CPD and CHD.
Figure 4: Kinetic curves for the reactions of nitrostyrene 1h with CPD (50–130 °C) and CHD at 110 °C.
Scheme 5: The Diels–Alder reaction of the nitrostyrene 1h with 1-methoxy-1,3-cyclohexadiene.
Scheme 6: Selected chemical transformations of norbornenes 2 (dr = exo:endo).
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
Graphical Abstract
Scheme 1: Overview of the synthetic methods for the carbazole-based heterohelicenes. i) Pd2dba3, xantphos, K3...
Scheme 2: Synthetic strategy for the carbazole-based [6]helicenes fused with an azine ring.
Scheme 3: Sonogashira coupling of compound 4b with phenylacetylene. i) Pd(PPh3)2Cl2, CuI, iPr2NH, DMSO, 80 °C...
Figure 1: Molecular structure of carbazole-based [6]helicenes 10a (a), 10b (b) and 10c (c) (X-ray data).
Figure 2: Crystal packing of carbazole-based [6]helicenes 10a (a, b), 10b (c,d) and 10c (e). Hydrogen atoms a...
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
Graphical Abstract
Scheme 1: Synthesis of a C8-linker-modified adenosine derivative. (a) 4 equiv TBDMS-Cl, 5 equiv imidazole, DM...
Figure 1: Characterization and assignment of the TBDMS isomers via HSQC (red) and HMBC (blue) NMR measurement...
Scheme 2: New synthetic route to the C8-linker modified adenosine building block. (a) i) 1.2 equiv di-tert-bu...
On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C
- Anwei Hou and
- Jeroen S. Dickschat
Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231
- through reactions that are classified as σ-bond cleavages, α-fragmentations, inductive cleavages, McLafferty rearrangements [11], retro-Diels–Alder fragmentations [12][13], and the recently observed unusual radical-induced retro-Cope rearrangement (herein, “retro” indicates that the mass spectrometric
Graphical Abstract
Figure 1: The structures of the bacterial sesterterpenes sestermobaraenes A–F (1–6) and sestermobaraol (7) fr...
Figure 2: Position-specific mass shift analyses for 1. Carbons that contribute fully to the formation of a fr...
Scheme 1: The EIMS fragmentation mechanisms for 1 explaining the formation of the fragment ions at m/z = 325,...
Scheme 2: The EIMS fragmentation mechanisms for 1 explaining the formation of fragment ions at m/z = 206 and ...
Figure 3: Position-specific mass shift analyses for 2. The carbons that contribute fully to the formation of ...
Scheme 3: The EIMS fragmentation mechanisms for 2 explaining the formation of the fragment ions at m/z = 325,...
Scheme 4: The EIMS fragmentation mechanisms for 2 explaining the formation of the fragment ions at m/z = 203 ...
Figure 4: The position-specific mass shift analyses for 3. Carbons that contribute fully to the formation of ...
Scheme 5: The EIMS fragmentation mechanisms for 3 explaining the formation of the fragment ions at m/z = 325,...
Scheme 6: The EIMS fragmentation mechanisms for 3 explaining the formation of the fragment ion at m/z = 206 a...
