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Search for "metalation" in Full Text gives 87 result(s) in Beilstein Journal of Organic Chemistry.
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
- variety of the Prins-cyclized products. The allyl metalation, followed by intramolecular Sakurai cyclization (IMSC) provides an efficient route to a variety of tetrahydropyran derivatives, as described by Marko and Leroy [68][69]. In these approaches, an initial ene reaction between an aldehyde 139 and
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 N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes
- Olga Bakhanovich,
- Viktor Khutorianskyi,
- Vladimir Motornov and
- Petr Beier
Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44
- of pyrroles to the 3,4-disubstituted derivatives is challenging because an electrophilic aromatic substitution of pyrroles or the metalation of N-substituted pyrroles and the subsequent reaction with electrophiles take place in position two of the ring [6][7]. Recently, N-sulfonyl-1,2,3-triazoles
- than the nitrile group and again the 3,4-disubstituted pyrrole 4 regioisomer dominated over the 2,4-disubstitued pyrrole 4’ (Scheme 4). To demonstrate the compatibility of the formed N-perfluoroalkylpyrroles with the conditions of pyrrole derivatization by metalation in position two and reaction with
- , agrochemicals, and functional materials. Transformation of N-sulfonyl-1,2,3-triazoles to pyrroles via metal iminocarbenes. Transannulation of triazoles 2 with phenylacetylene. Transannulation of N-perfluoroalkyl-1,2,3-triazoles with aliphatic alkynes. Reaction of 1a with hex-5-ynenitrile. Metalation and
Graphical Abstract
Figure 1: Selected pyrrole-containing natural products, drugs, agrochemicals, and functional materials.
Scheme 1: Transformation of N-sulfonyl-1,2,3-triazoles to pyrroles via metal iminocarbenes.
Scheme 2: Transannulation of triazoles 2 with phenylacetylene.
Scheme 3: Transannulation of N-perfluoroalkyl-1,2,3-triazoles with aliphatic alkynes.
Scheme 4: Reaction of 1a with hex-5-ynenitrile.
Scheme 5: Metalation and carboxylation of in situ-prepared pyrrole 2a.
Scheme 6: Plausible mechanism for rhodium-catalyzed transannulation of N-perfluoroalkyl-1,2,3-triazoles with ...
Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners
- Shakeel Alvi and
- Rashid Ali
Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186
- ) complex 123 as an endo-coordinated complex at the concave side. The complex 123a was prepared through the metalation of sumanene involving ligand exchange with a cyclopentadienyl (Cp) group of ferrocene by heating in the presence of Al powder and AlCl3 under solvent-free conditions followed by a counter
Graphical Abstract
Figure 1: Representation of corannulene (1) and sumanene (2), the subunits of fullerene (C60).
Scheme 1: Mehta’s unsuccessful effort for the synthesis of sumanene scaffold 2.
Scheme 2: First synthesis of sumanene 2 by Sakurai et al. from norbornadiene 10.
Scheme 3: Synthesis of trimethylsumanene 28 from easily accessible norbornadiene (10).
Scheme 4: Generation of anions 29–31 and the preparation of tris(trimethylsilyl)sumanene 32.
Scheme 5: Synthesis of tri- and hexa-substituted sumanene derivatives.
Scheme 6: Synthesis of bowl-shaped π-extended sumanene derivatives 37a–f.
Scheme 7: Synthesis of monooxasumanene 38, trioxosumanene 40 along with imination of them.
Scheme 8: Synthesis of trimethylsumanenetrione 46 and exo-functionalized products 45a,b.
Scheme 9: Synthesis of bisumanenylidene 47 and sumanene dimer 48 from 2.
Scheme 10: The mono-substitution of 2 to generate diverse mono-sumanene derivatives 49a–d.
Scheme 11: Synthesis of sumanene building block 53 useful for further extension.
Scheme 12: Synthesis of hexafluorosumanene derivative 55 by Sakurai and co-workers.
Scheme 13: Preparation of sumanene-based carbene 60 and its reaction with cyclohexane.
Scheme 14: Barton–Kellogg reaction for the synthesis of sterically hindered alkenes.
Scheme 15: Synthesis of hydroxysumanene 68 by employing Baeyer–Villiger oxidation.
Scheme 16: Synthesis of sumanene derivatives having functionality at an internal carbon.
Scheme 17: Mechanism for nucleophilic substitution reaction at the internal carbon.
Scheme 18: Synthesis of diverse monosubstituted sumanene derivatives.
Scheme 19: Synthesis of di- and trisubstituted sumanene derivatives from sumanene (2).
Scheme 20: Preparation of monochlorosumanene 88 and hydrogenation of sumanene (2).
Scheme 21: The dimer 90 and bissumanenyl 92 achieved from halosumannes.
Scheme 22: Pyrenylsumanene 93 involving the Suzuki-coupling as a key transformation.
Scheme 23: Synthesis of various hexaarylsumanene derivatives using the Suzuki-coupling reaction.
Scheme 24: Synthesis of hexasubstituted sumanene derivatives 96 and 97.
Scheme 25: Synthesis of thioalkylsumanenes via an aromatic nucleophilic substitution reaction.
Scheme 26: Synthesis of tris(ethoxycarbonylethenyl)sumanene derivative 108.
Scheme 27: Synthesis of ferrocenyl-based sumanene derivatives.
Scheme 28: Synthesis of sumanenylferrocene architectures 118 and 119 via Negishi coupling.
Scheme 29: Diosmylation and the synthesis of phenylboronate ester 121 of sumanene.
Scheme 30: Synthesis of the iron-complex of sumanene.
Scheme 31: Synthesis of tri- and mononuclear sumanenyl zirconocene complexes.
Scheme 32: Synthesis of [CpRu(η6-sumanene)]PF6.
Scheme 33: Preparation of sumanene-based porous coordination networks 127 (spherical tetramer units) and 128 (...
Scheme 34: Synthesis of sumanenylhafnocene complexes 129 and 130.
Scheme 35: Synthesis of 134 and 135 along with PdII coordination complex 136.
Scheme 36: Synthesis of alkali metals sumanene complex K7(C21H102−)2(C21H93−)·8THF (137) containing di- and tr...
Scheme 37: The encapsulation of a Cs+ ion between two sumanenyl anions.
Scheme 38: Synthesis of monothiasumanene 140 and dithiasumanene 141 from 139.
Scheme 39: Synthesis of trithiasumanene 151 by Otsubo and his co-workers.
Scheme 40: Synthesis of trithiasumanene derivatives 155 and 156.
Scheme 41: Synthetic route towards hexathiolated trithiasumanenes 158.
Scheme 42: Synthesis of triselenasumanene 160 by Shao and teammates.
Scheme 43: Synthesis of tritellurasumanene derivatives from triphenylene skeletons.
Scheme 44: Synthesis of pyrazine-fused sumanene architectures through condensation reaction.
Scheme 45: Treatment of the trichalcogenasumanenes with diverse oxidative reagents.
Scheme 46: Ring-opening reaction with H2O2 and oxone of heterasumanenes 178 and 179.
Scheme 47: Synthesis of polycyclic compounds from sumanene derivatives.
Scheme 48: Synthesis of diimide-based heterocycles reported by Shao’s and co-workers.
Scheme 49: Synthesis of pristine trichalcogenasumanenes, 151, 205, and 206.
Scheme 50: Synthesis of trichalcogenasumanenes via hexaiodotriphenylene precursor 208.
Scheme 51: Synthesis of trisilasumanenes 214 and 215.
Scheme 52: Synthesis of trisilasumanene derivatives 218 and 219.
Scheme 53: Synthesis of novel trigermasumanene derivative 223.
Scheme 54: An attempt towards the synthesis of tristannasumanene derivative 228.
Scheme 55: Synthesis of triphosphasumanene trisulfide 232 from commercially available 229.
Scheme 56: The doping of sumanene derivatives with chalcogens (S, Se, Te) and phosphorus.
Scheme 57: Synthesis of heterasumanene containing three different heteroatoms.
Scheme 58: Synthesis of trichalcogenasumanene derivatives 240 and 179.
Scheme 59: Preparation of trichalcogenasumanenes 245 and 248.
Scheme 60: Design and synthesis of trichalcogenasumanene derivatives 252 and 178.
Scheme 61: Synthesis of spirosumanenes 264–269 and non-spiroheterasumanenes 258–263.
Scheme 62: Synthesis of sumanene-type hetero polycyclic compounds.
Scheme 63: Synthesis of triazasumanenes 288 and its sulfone congener 287.
Scheme 64: Synthesis of C3-symmetric chiral triaryltriazasumanenes via cross-coupling reaction.
Scheme 65: Synthesis of mononaphthosumanene 293 using Suzuki coupling as a key step.
Scheme 66: Synthesis of di- and trinaphthosumanene derivatives 302–304.
Scheme 67: Synthesis of hemifullerene skeletons by Hirao’s group.
Scheme 68: Design and construction of C70 fragment from a C60 sumanene fragment.
Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents
- Paola Vitale,
- Luciana Cicco,
- Ilaria Cellamare,
- Filippo M. Perna,
- Antonio Salomone and
- Vito Capriati
Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158
- ], (c) carbon–sulfur bond-forming reactions [9], (d) directed ortho-metalation and nucleophilic acyl substitution strategies [10], (e) Pd-catalyzed aminocarbonylation of aryl iodides, Suzuki–Miyaura and Sonogashira cross-coupling reactions [11][12][13], (f) Cu-catalyzed C–N coupling reactions [14], and
Graphical Abstract
Scheme 1: One-pot synthesis of 2,5-diarylpyrazines (A) (path a) or 2-aroyl-(4 or 5)-aryl-(1H)-imidazoles (B) ...
Scheme 2: Transformation of phenacyl bromide (1a) in ChCl/Gly into phenacyl azide (2a) and 2-benzoyl-(4 or 5)...
Scheme 3: Synthesis of 2-aroyl-(4 or 5)-aryl-(1H)-imidazoles 3. Scope of the reaction. Typical conditions: 1 ...
Scheme 4: Proposed mechanism for the formation of 2-aroyl-(4 or 5)-aryl-(1H)-imidazoles 3/3' from α-phenacyl ...
Scheme 5: Proposed mechanism for the formation of 2-benzoyl-(4 or 5)-phenyl-(1H)-imidazoles 3a/3a' and 2,4-di...
Scheme 6: Scope of the synthesis of 2,4-diaroyl-6-arylpyrimidines 7. Typical conditions: 2 (0.3 mmol), Et3N (...
When metal-catalyzed C–H functionalization meets visible-light photocatalysis
- Lucas Guillemard and
- Joanna Wencel-Delord
Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147
- undergoes cyclometalation via a concerted metalation–deprotonation (CMD) process furnishing a cyclometalated intermediate. Thereafter, coordination and subsequent insertion of the alkyne into the Co–C bond delivers a seven-membered cobaltacycle. The desired coupling product is then liberated by reductive
- et al., allowing the synthesis of N-heterocycles such as indoles and pyrroles. The targeted heterocyclic products were obtained by cyclization of acetanilides with alkyne derivatives via a direct ortho-metalation pathway (Figure 17) [79]. Acetyl substituents acted as DG in this transformation
- heterocyclic compounds in decreased yields. Once again, the use of Ru-based photocatalyst in combination with molecular oxygen as a terminal oxidant was crucial in this cyclization/C–H functionalization pathway (Figure 18). The classical C–H activation cycle involves an initial amide-directed ortho-metalation
Graphical Abstract
Figure 1: Concept of dual synergistic catalysis.
Figure 2: Classification of catalytic systems involving two catalysts.
Figure 3: General mechanism for the dual nickel/photoredox catalytic system.
Figure 4: General mechanisms for C–H activation catalysis involving different reoxidation strategies.
Figure 5: Indole synthesis via dual C–H activation/photoredox catalysis.
Figure 6: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 7: Oxidative Heck reaction on arenes via the dual catalysis.
Figure 8: Proposed mechanism for the Heck reaction on arenes via dual catalysis.
Figure 9: Oxidative Heck reaction on phenols via the dual catalysis.
Figure 10: Proposed mechanism for the Heck reaction on phenols via dual catalysis.
Figure 11: Carbazole synthesis via dual C–H activation/photoredox catalysis.
Figure 12: Proposed mechanism for the carbazole synthesis via dual catalysis.
Figure 13: Carbonylation of enamides via the dual C–H activation/photoredox catalysis.
Figure 14: Proposed mechanism for carbonylation of enamides via dual catalysis.
Figure 15: Annulation of benzamides via the dual C–H activation/photoredox catalysis.
Figure 16: Proposed mechanism for the annulation of benzamides via dual catalysis.
Figure 17: Synthesis of indoles via the dual C–H activation/photoredox catalysis.
Figure 18: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 19: General concept of dual catalysis merging C–H activation and photoredox catalysis.
Figure 20: The first example of dual catalysis merging C–H activation and photoredox catalysis.
Figure 21: Proposed mechanism for the C–H arylation with diazonium salts via dual catalysis.
Figure 22: Dual catalysis merging C–H activation/photoredox using diaryliodonium salts.
Figure 23: Direct arylation via the dual catalytic system reported by Xu.
Figure 24: Direct arylation via dual catalytic system reported by Balaraman.
Figure 25: Direct arylation via dual catalytic system reported by Guo.
Figure 26: C(sp3)–H bond arylation via the dual Pd/photoredox catalytic system.
Figure 27: Acetanilide derivatives acylation via the dual C–H activation/photoredox catalysis.
Figure 28: Proposed mechanism for the C–H acylation with α-ketoacids via dual catalysis.
Figure 29: Acylation of azobenzenes via the dual catalysis C–H activation/photoredox.
Figure 30: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 31: Proposed mechanism for the C2-acylation of indoles with aldehydes via dual catalysis.
Figure 32: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 33: Perfluoroalkylation of arenes via the dual C–H activation/photoredox catalysis.
Figure 34: Proposed mechanism for perfluoroalkylation of arenes via dual catalysis.
Figure 35: Sulfonylation of 1-naphthylamides via the dual C–H activation/photoredox catalysis.
Figure 36: Proposed mechanism for sulfonylation of 1-naphthylamides via dual catalysis.
Figure 37: meta-C–H Alkylation of arenes via visible-light metallaphotocatalysis.
Figure 38: Alternative procedure for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 39: Proposed mechanism for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 40: C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 41: Proposed mechanism for C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 42: Undirected C–H aryl–aryl cross coupling via dual gold/photoredox catalysis.
Figure 43: Proposed mechanism for the undirected C–H aryl–aryl cross-coupling via dual catalysis.
Figure 44: Undirected C–H arylation of (hetero)arenes via dual manganese/photoredox catalysis.
Figure 45: Proposed mechanism for the undirected arylation of (hetero)arenes via dual catalysis.
Figure 46: Photoinduced C–H arylation of azoles via copper catalysis.
Figure 47: Photo-induced C–H chalcogenation of azoles via copper catalysis.
Figure 48: Decarboxylative C–H adamantylation of azoles via dual cobalt/photoredox catalysis.
Figure 49: Proposed mechanism for the C–H adamantylation of azoles via dual catalysis.
Figure 50: General mechanisms for the “classical” (left) and Cu-free variant (right) Sonogoshira reaction.
Figure 51: First example of a dual palladium/photoredox catalysis for Sonogashira-type couplings.
Figure 52: Arylation of terminal alkynes with diazonium salts via dual gold/photoredox catalysis.
Figure 53: Proposed mechanism for the arylation of terminal alkynes via dual catalysis.
Figure 54: C–H Alkylation of alcohols promoted by H-atom transfer (HAT).
Figure 55: Proposed mechanism for the C–H alkylation of alcohols promoted by HAT.
Figure 56: C(sp3)–H arylation of latent nucleophiles promoted by H-atom transfer.
Figure 57: Proposed mechanism for the C(sp3)–H arylation of latent nucleophiles promoted by HAT.
Figure 58: Direct α-arylation of alcohols promoted by H-atom transfer.
Figure 59: Proposed mechanism for the direct α-arylation of alcohols promoted by HAT.
Figure 60: C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 61: Proposed mechanism for the C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 62: C–H functionalization of nucleophiles via excited ketone/nickel dual catalysis.
Figure 63: Proposed mechanism for the C–H functionalization enabled by excited ketones.
Figure 64: Selective sp3–sp3 cross-coupling promoted by H-atom transfer.
Figure 65: Proposed mechanism for the selective sp3–sp3 cross-coupling promoted by HAT.
Figure 66: Direct C(sp3)–H acylation of amines via dual Ni/photoredox catalysis.
Figure 67: Proposed mechanism for the C–H acylation of amines via dual Ni/photoredox catalysis.
Figure 68: C–H hydroalkylation of internal alkynes via dual Ni/photoredox catalysis.
Figure 69: Proposed mechanism for the C–H hydroalkylation of internal alkynes.
Figure 70: Alternative procedure for the C–H hydroalkylation of ynones, ynoates, and ynamides.
Figure 71: Allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 72: Proposed mechanism for the allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 73: Asymmetric allylation of aldehydes via dual Cr/photoredox catalysis.
Figure 74: Proposed mechanism for the asymmetric allylation of aldehydes via dual catalysis.
Figure 75: Aldehyde C–H functionalization promoted by H-atom transfer.
Figure 76: Proposed mechanism for the C–H functionalization of aldehydes promoted by HAT.
Figure 77: Direct C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 78: Proposed mechanism for the C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 79: Direct C–H trifluoromethylation of strong aliphatic bonds promoted by HAT.
Figure 80: Proposed mechanism for the C–H trifluoromethylation of strong aliphatic bonds.
Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization
- Dominik Göbel,
- Marius Friedrich,
- Enno Lork and
- Boris J. Nachtsheim
Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139
- . Condensation with 2-amino-2-methylpropan-1-ol and oxidation with NBS yielded oxazoline 6 in a good yield. Directed ortho-metalation utilizing TMPMgCl·LiCl under mild conditions and subsequent smooth formylation with DMF afforded benzaldehyde 7 (see Scheme 2). Due to rapid decomposition of 7 under ambient and
- of the ortho-bromine substituent was again accomplished by metalation using TMPMgCl·LiCl and subsequent reaction with 1,2-dibromotetrachloroethane to afford 11 in 76% yield. A second bromination at the benzylic position provided the dibrominated derivative 12 in 66% yield. The substitution reaction
- -carbaldehyde 16 in excellent yield over three steps. Conversion to the 2-aryloxazoline 17 was accomplished in 92% yield using the same method as described for the synthesis of 6 and 10. ortho-Metalation with TMPMgCl·LiCl [70] and conversion of the magnesiated species with DMF to carbaldehyde 18 was followed by
Graphical Abstract
Scheme 1: a) Schematic depiction of the Jablonski diagram. b) Schematic representation of El-Sayed’s rule.
Figure 1: Top: literature examples of organic compounds showing RTP in the crystalline state (a) and in solut...
Scheme 2: Reaction conditions for para-bromobenzaldehyde 3: a) 1) 2-amino-2-methylpropan-1-ol, 4 Å MS, CH2Cl2...
Scheme 3: Reaction conditions: a) Br2, Fe powder, CHCl3, 0 °C, 4 h, 99%; b) KOH, KI, MeI, DMSO, 25 °C, 18 h, ...
Scheme 4: Reaction conditions: a) 1) NaH, THF, 0 °C, 30 min; 2) MeI, THF, 0 °C to 25 °C, 2 h, 99%; b) 1) MeOT...
Scheme 5: a) CuAAC reactions of azide-functionalized bromocarbaldehydes 3, 4 and 5 with terminal alkynes to t...
Figure 2: a) Normalized UV–vis absorption spectra of 3 (blue line), 34 (olive line), 4 (green line) and 38 (r...
Figure 3: a) Normalized UV–vis absorption spectra of 5 (blue line), 16 (green line), 42 (olive line) and 45 (...
Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach
- Rhys A. Lippa,
- John A. Murphy and
- Tim N. Barrett
Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134
- cores for these compounds in high yields (63–83% over 3 steps) with no need for chromatography. Key to this transformation is the phosphoramidate protecting group, which is stable to metalation steps. Keywords: arginine; Horner–Wadsworth–Emmons; integrin; phosphoramidate; tetrahydronaphthyridine
- tetrahydronaphthyridine in THF at this temperature. The use of iPrMgCl, a strong but room temperature-stable base, gave the highest conversion to phosphoramidate 13. Further investigation into the use of iPrMgCl revealed that a quantitative conversion was achieved at ambient temperature with a metalation time of <1
Graphical Abstract
Figure 1: The Arg–Gly–Asp tripeptide sequence and examples of tetrahydro-1,8-naphthyridine-containing integri...
Scheme 1: Commonly used synthetic routes to tetrahydro-1,8-naphthyridine moieties by hydrogenation of saturat...
Scheme 2: Previous synthetic route to fluoropyrrolidine 6 utilising a Wittig reaction and the novel, higher y...
Scheme 3: Synthesis of phosphoramidate 9 from tetrahydro-1,8-naphthyridine 8. Conditions: s-BuLi (3 equiv), d...
Scheme 4: Mono- and diphosphorylation of tetrahydro-1,8-naphthyridine 11. Conditions: (i) s-BuLi (2 equiv), d...
Scheme 5: Synthesis of amine 6 from phosphonate 7 and aldehyde 5. Conditions: (i) T3P® (50% w/w in DCM, 3 equ...
Scheme 6: Monodeuteration of 13 as observed by 1H and 13C NMR. Conditions: s-BuLi (3 equiv), THF, −42 °C, 20 ...
Scheme 7: Sequential diphosphorylation of tetrahydronaphthyridine 11. Conditions: (i) iPrMgCl (1.5 equiv), TH...
Scheme 8: Possible mechanistic pathways for the formation of dimer 28. Conditions: KOt-Bu, THF, 1 h, 68% yiel...
Scheme 9: Alkylation of phosphoramidate 13 by iodide 29 to afford compound 30 and byproducts alcohol 31 and d...
Towards triptycene functionalization and triptycene-linked porphyrin arrays
- Gemma M. Locke,
- Keith J. Flanagan and
- Mathias O. Senge
Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70
- as before. After silica gel column chromatography, a dark purple solid of 16 was isolated in 8% yield. The unsymmetrically substituted triptycene 12 was utilized for several other cross-coupling reactions, including one with the dibrominated porphyrin 17c which was prepared via metalation of 17b and
Graphical Abstract
Figure 1: Triptycene as a scaffold and selected porphyrin and BODIPY arrays.
Scheme 1: Sonogashira cross-coupling reactions to form symmetric porphyrin and BODIPY triptycene-linked dyads....
Scheme 2: Sonogashira cross-coupling reactions to form a triptycene-substituted porphyrin monomer and an unsy...
Scheme 3: Synthesis of the triptycene-porphyrin-triptycene complex 18.
Figure 2: Single crystal X-ray structure of triptycene 5. (a) Molecular structure of 5 in the crystal with hy...
Figure 3: Single crystal X-ray structure of triptycene-linked zinc-nickel porphyrin dimer 16 showing the conf...
Figure 4: Views of the single crystal X-ray structure of triptycene-linked zinc-nickel porphyrin dimer 16 sho...
Figure 5: Expanded structure view of the triptycene-linked zinc-nickel porphyrin dimer 16 showing the repeati...
Figure 6: UV–vis of symmetric and unsymmetric triptycene porphyrin dimers 9 and 16, and the triptycene porphy...
Figure 7: Emission spectrum of symmetric and unsymmetric triptycene-linked porphyrin dimers 9 and 16, and a t...
Figure 8: Compounds used for spectroscopic comparisons.
Figure 9: UV–vis spectra of various porphyrin/BODIPY dimers with different linker groups in CHCl3.
Figure 10: Fluorescence emission spectrum of various porphyrin/BODIPY dimers with different linker groups in C...
Room-temperature Pd/Ag direct arylation enabled by a radical pathway
- Amy L. Mayhugh and
- Christine K. Luscombe
Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36
- proposed mechanisms for direct arylation (Scheme 2). Amongst these mechanisms, the most widely accepted is the concerted metalation–deprotonation (CMD) pathway [21]. Within the indole direct-arylation literature, however, there remains much discussion of an electrophilic metalation mechanism, with the
Graphical Abstract
Scheme 1: A high yielding, highly selective room-temperature direct arylation reaction between indole and iod...
Figure 1: 1H NMR (500 MHz, CDCl3) of (a) 5-iodo-1-octylindole monomer (b) PIn prepared according to condition...
Figure 2: MALDI–TOF MS of PIn, indicating octylindole repeat units with three different types of end groups. ...
Scheme 2: Commonly discussed mechanisms for C2 selective direct arylation, none containing radical intermedia...
Scheme 3: Proposed mechanism for palladium radical involved reaction between indole and iodobenzene.
Scheme 4: Radical trap effects on literature methods for the direct arylation at room temperature. A) From re...
Architecture and synthesis of P,N-heterocyclic phosphine ligands
- Wisdom A. Munzeiwa,
- Bernard Omondi and
- Vincent O. Nyamori
Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35
- where the metalated organohalogen compound is reacted with the halogen phosphine. Alternatively, the metal phosphide can be reacted with an organohalogen compound leading to the desired product. The most commonly used trans-metalation reagents are Grignard [54] or organolithium reagents [55] and other
- suitable bases. The metalation reaction is prone to side reactions when carried out at higher temperatures and as such, the reaction must be carried out below 0 °C. For example, pyridyllithium derivatives as intermediates can be subjected to deprotonation, substrate addition and pyridine formation due to
- nucleophiles compared to organometallic or metal phosphides generated through metalation processes. Hayashi et al. [66] used tris(trimethylsilyl)phosphine to control the nucleophilic substitution in the preparation of P,N-(phosphino)triazine ligands (Scheme 5). It was shown that the use of other nucleophiles
Graphical Abstract
Scheme 1: Synthesis of pyridylphosphine ligands.
Figure 1: Pyridylphosphine ligands.
Scheme 2: Synthesis of piperidyl- and oxazinylphosphine ligands.
Scheme 3: Synthesis of linear multi-chelate pyridylphosphine ligands.
Scheme 4: Synthesis of chiral acetal pyridylphosphine ligands.
Scheme 5: Synthesis of diphenylphosphine-substituted triazine ligands.
Scheme 6: Synthesis of (pyridine-2-ylmethyl)phosphine ligands.
Scheme 7: Synthesis of diphosphine pyrrole ligands.
Scheme 8: Synthesis of 4,5-diazafluorenylphosphine ligands.
Scheme 9: Synthesis of thioether-containing pyridyldiphosphine ligands starting from ethylene sulfide and dip...
Scheme 10: Synthesis of monoterpene-derived phosphine pyridine ligands.
Scheme 11: Synthesis of N-phenylphosphine-substituted imidazole ligands.
Scheme 12: Synthesis of triazol-4-ylphosphine ligands.
Scheme 13: Synthesis of phosphanyltriazolopyridines and product selectivity depending on the substituents’ eff...
Scheme 14: Synthesis of PTA-phosphine ligands.
Scheme 15: Synthesis of isomeric phosphine dipyrazole ligands by varying the reaction temperature.
Scheme 16: Synthesis of N-tethered phosphine imidazolium ligands (route A) and diphosphine imidazolium ligands...
Scheme 17: Synthesis of {1-[2-(pyridin-2-yl)- (R = CH) and {1-[2-(pyrazin-2-yl)quinazolin-4-yl]naphthalen-2-yl...
Scheme 18: Synthesis of oxazolylindolylphosphine ligands 102.
Scheme 19: Synthesis of pyrrolylphosphine ligands.
Scheme 20: Synthesis of phosphine guanidinium ligands.
Scheme 21: Synthesis of a polydentate aminophosphine ligand.
Scheme 22: Synthesis of quinolylphosphine ligands.
Scheme 23: Synthesis of N-(triazolylmethyl)phosphanamine ligands.
Figure 2: Triazolylphosphanamine ligands synthesized by Wassenaar’s method [22].
Scheme 24: Synthesis of oxazaphosphorines.
Scheme 25: Synthesis of paracyclophane pyridylphosphine ligands.
Scheme 26: Synthesis of triazolylphosphine ligands.
Figure 3: Click-phosphine ligands.
Scheme 27: Ferrocenyl pyridylphosphine imine ligands.
Scheme 28: Synthesis of phosphinooxazolines (PHOX).
Scheme 29: Synthesis of ferrocenylphosphine oxazoles.
Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo
- Alexander Sailer,
- Franziska Ermer,
- Yvonne Kraus,
- Rebekkah Bingham,
- Ferdinand H. Lutter,
- Julia Ahlfeld and
- Oliver Thorn-Seshold
Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14
- , lithium diisopropylamide (LDA)-mediated cyclisation of 2-(methylthio)benzamides, which were obtained by directed ortho-metalation of the respective benzamides followed by quenching with dimethyl disulfide [27] (Supporting Information File 1, Scheme S1). In general, we found the LDA-mediated cyclisation
Graphical Abstract
Figure 1: a) The potent tubulin inhibitor colchicine as a lead scaffold led to the development of the HOTub g...
Figure 2: Chemical structures of HITubs. Key variations with respect to HITub-4 are highlighted in dashed box...
Figure 3: Photocharacterisation of HITub-4. a) Photochemical and thermal isomerisation. b) UV–vis spectra aft...
Figure 4: a) Resazurin reduction assay for HITub-4 and nocodazole in HeLa cells (n = 3), demonstrating the di...
Figure 5: Confocal microscopy images of immunofluorescently labelled MT networks after treatment with HITubs ...
Figure 6: Cell cycle analysis of HITub-4-treated cells. a) and b) (Z)-HITub-4 caused significant G2/M arrest ...
Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids
- Benedikt C. Melzer,
- Alois Plodek and
- Franz Bracher
Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222
- metalation at C-5 with TMPMgCl∙LiCl at −40 °C. Quenching with various electrophiles gives a broad range of 5-substituted products, which are building blocks for the synthesis of heterocyclic natural products and analogues thereof. In combination with a Parham-type cyclization a novel approach to pyrido[4,3,2
- -mn]acridones has been worked out. Keywords: alkaloids; cyclization; metalation; naphthyridine; pyridoacridine; Introduction Polycyclic aromatic alkaloids are a unique class of natural products with a broad pattern of biological activities. One of the most prominent classes are the so-called
- 4,5-disubstituted benzo[c][2,7]naphthyridines utilizing ortho-directed ring metalation/biaryl cross-coupling strategies [9]. 4-Chlorobenzo[c][2,7]naphthyridine (9a) was conveniently converted into other 4-substituted benzo[c][2,7]naphthyridines by substitution reactions with nucleophiles (alcoholates
Graphical Abstract
Figure 1: Marine pyridoacridine alkaloids amphimedine (1), ascididemin (2), kuanoniamine A (3), styelsamine D...
Figure 2: A–C): Published methods for the synthesis of 4,5-disubstituted benzo[c][2,7]naphthyridines; D) New ...
Scheme 1: Regioselective metalation of 4-bromobenzo[c][2,7]naphthyridine (9d) and subsequent conversion into ...
Scheme 2: Outcome of a D2O quenching experiment after metalation of 4-bromobenzo[c][2,7]naphthyridine (9d).
Scheme 3: Synthesis of 5-substituted 4-bromobenzo[c][2,7]naphthyridines via regioselective metalation of 9d u...
Scheme 4: Attempted synthesis of kuanoniamine A (3).
Scheme 5: Synthesis of pyrido[4,3,2-mn]acridone 22 starting from 20a via bromine–magnesium exchange reaction ...
1,2,3-Triazolium macrocycles in supramolecular chemistry
- Mastaneh Safarnejad Shad,
- Pulikkal Veettil Santhini and
- Wim Dehaen
Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211
- triazole containing dialdehyde and binaphthyl with dipyrromethene, followed by zinc metalation and subsequent reaction with MeI resulted in the synthesis of the two-component catalytic system 16 (Figure 13). Here, the cooperative effect of nucleophilic triazolium moieties, their counter ion near the
Graphical Abstract
Figure 1: Hydrogen, halogen or chalcogen bonding to anions within a bistriazolium macrocycle.
Figure 2: Main synthetic strategies towards macrocyclic triazoliums.
Figure 3: Chemical structure of compound 1 (1a, 1b and 1c) and 2.
Figure 4: Chemical structure of compound 3 and 4.
Figure 5: Chemical structure of compound 5.
Figure 6: Chemical structure of compound 6.
Figure 7: Chemical structure of compound 7.
Figure 8: Chemical structure of compound 8.
Figure 9: Chemical structures of compound 9.
Figure 10: Chemical structures of compound 10, 11 and 12.
Figure 11: Chemical structure of compound 13.
Figure 12: Chemical structure of compound 15 including the sigma-connected TCNQ dimer.
Figure 13: Chemical structure of compound 16 for the kinetic resolution of epoxides.
Figure 14: Chemical structure of compound 17a (bisnaphtho crown ether shown).
Figure 15: Jump rope in molecular double-lasso compounds 18.
Figure 16: Chemical structure of compound 19 and acid–base triggered motions.
Attempted synthesis of a meta-metalated calix[4]arene
- Christopher D. Jurisch and
- Gareth E. Arnott
Beilstein J. Org. Chem. 2019, 15, 1996–2002, doi:10.3762/bjoc.15.195
- , followed by metalation of the triazolium salt 4 with silver oxide, which was immediately transmetalated with [RuCl2(p-cymene)]2. In our hands, purification using Albrecht’s trituration method was unsuccessful, however, neutral alumina column chromatography produced the desired model ruthenium metallocycle
- quantitative yield. In the final step towards a mesoionic calix[4]arene metallocycle, the synthesis was unfortunately not as trivial or as successful as we had hoped. The metalation reaction, using the methods described by Albrecht and co-workers [19], were repeated a number of times. In all cases the problem
Graphical Abstract
Figure 1: Inherent chirality generated by meta-substitution – the two structures are non-superposable mirror ...
Figure 2: General approach by Albrecht for MIC directed cyclometalation via C–H activation; M = Ru(II), Ir(II...
Figure 3: Concept of cyclometalated calix[4]arene target.
Scheme 1: Synthesis of model mesoionic carbene 5.
Scheme 2: Attempted Ullmann-coupling to give monoazide 7.
Scheme 3: Synthesis of monoazidocalix[4]arene 7 under optimized conditions.
Scheme 4: Synthesis of the putative calix[4]arene mesoionic carbene ruthenium complex 13.
Figure 4: High-resolution mass spectrum (ESI+) of putative ruthenacycle calix[4]arene 13.
Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage
- Gagandeep Kour Reen,
- Ashok Kumar and
- Pratibha Sharma
Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165
Graphical Abstract
Figure 1: Various drugs having IP nucleus.
Figure 2: Participation percentage of various TMs for the syntheses of IPs.
Scheme 1: CuI–NaHSO4·SiO2-catalyzed synthesis of imidazo[1,2-a]pyridines.
Scheme 2: Experimental examination of reaction conditions.
Scheme 3: One-pot tandem reaction for the synthesis of 2-haloimidazopyridines.
Scheme 4: Mechanistic scheme for the synthesis of 2-haloimidazopyridine.
Scheme 5: Copper-MOF-catalyzed three-component reaction (3-CR) for imidazo[1,2-a]pyridines.
Scheme 6: Mechanism for copper-MOF-driven synthesis.
Scheme 7: Heterogeneous synthesis via titania-supported CuCl2.
Scheme 8: Mechanism involving oxidative C–H functionalization.
Scheme 9: Heterogeneous synthesis of IPs.
Scheme 10: One-pot regiospecific synthesis of imidazo[1,2-a]pyridines.
Scheme 11: Vinyl azide as an unprecedented substrate for imidazo[1,2-a]pyridines.
Scheme 12: Radical pathway.
Scheme 13: Cu(I)-catalyzed transannulation approach for imidazo[1,5-a]pyridines.
Scheme 14: Plausible radical pathway for the synthesis of imidazo[1,5-a]pyridines.
Scheme 15: A solvent-free domino reaction for imidazo[1,2-a]pyridines.
Scheme 16: Cu-NPs-mediated synthesis of imidazo[1,2-a]pyridines.
Scheme 17: CuI-catalyzed synthesis of isoxazolylimidazo[1,2-a]pyridines.
Scheme 18: Functionalization of 4-bromo derivative via Sonogashira coupling reaction.
Scheme 19: A plausible reaction pathway.
Scheme 20: Cu(I)-catalyzed intramolecular oxidative C–H amidation reaction.
Scheme 21: One-pot synthetic reaction for imidazo[1,2-a]pyridine.
Scheme 22: Plausible reaction mechanism.
Scheme 23: Cu(OAc)2-promoted synthesis of imidazo[1,2-a]pyridines.
Scheme 24: Mechanism for aminomethylation/cycloisomerization of propiolates with imines.
Scheme 25: Three-component synthesis of imidazo[1,2-a]pyridines.
Figure 3: Scope of pyridin-2(1H)-ones and acetophenones.
Scheme 26: CuO NPS-promoted A3 coupling reaction.
Scheme 27: Cu(II)-catalyzed C–N bond formation reaction.
Scheme 28: Mechanism involving Chan–Lam/Ullmann coupling.
Scheme 29: Synthesis of formyl-substituted imidazo[1,2-a]pyridines.
Scheme 30: A tandem sp3 C–H amination reaction.
Scheme 31: Probable mechanistic approach.
Scheme 32: Dual catalytic system for imidazo[1,2-a]pyridines.
Scheme 33: Tentative mechanism.
Scheme 34: CuO/CuAl2O4/ᴅ-glucose-promoted 3-CCR.
Scheme 35: A tandem CuOx/OMS-2-based synthetic strategy.
Figure 4: Biomimetic catalytic oxidation in the presence of electron-transfer mediators (ETMs).
Scheme 36: Control experiment.
Scheme 37: Copper-catalyzed C(sp3)–H aminatin reaction.
Scheme 38: Reaction of secondary amines.
Scheme 39: Probable mechanistic pathway.
Scheme 40: Coupling reaction of α-azidoketones.
Scheme 41: Probable pathway.
Scheme 42: Probable mechanism with free energy calculations.
Scheme 43: MCR for cyanated IP synthesis.
Scheme 44: Substrate scope for the reaction.
Scheme 45: Reaction mechanism.
Scheme 46: Probable mechanistic pathway for Cu/ZnAl2O4-catalyzed reaction.
Scheme 47: Copper-catalyzed double oxidative C–H amination reaction.
Scheme 48: Application towards different coupling reactions.
Scheme 49: Reaction mechanism.
Scheme 50: Condensation–cyclization approach for the synthesis of 1,3-diarylated imidazo[1,5-a]pyridines.
Scheme 51: Optimized reaction conditions.
Scheme 52: One-pot 2-CR.
Scheme 53: One-pot 3-CR without the isolation of chalcone.
Scheme 54: Copper–Pybox-catalyzed cyclization reaction.
Scheme 55: Mechanistic pathway catalyzed by Cu–Pybox complex.
Scheme 56: Cu(II)-promoted C(sp3)-H amination reaction.
Scheme 57: Wider substrate applicability for the reaction.
Scheme 58: Plausible reaction mechanism.
Scheme 59: CuI assisted C–N cross-coupling reaction.
Scheme 60: Probable reaction mechanism involving sp3 C–H amination.
Scheme 61: One-pot MCR-catalyzed by CoFe2O4/CNT-Cu.
Scheme 62: Mechanistic pathway.
Scheme 63: Synthetic scheme for 3-nitroimidazo[1,2-a]pyridines.
Scheme 64: Plausible mechanism for CuBr-catalyzed reaction.
Scheme 65: Regioselective synthesis of halo-substituted imidazo[1,2-a]pyridines.
Scheme 66: Synthesis of 2-phenylimidazo[1,2-a]pyridines.
Scheme 67: Synthesis of diarylated compounds.
Scheme 68: CuBr2-mediated one-pot two-component oxidative coupling reaction.
Scheme 69: Decarboxylative cyclization route to synthesize 1,3-diarylimidazo[1,5-a]pyridines.
Scheme 70: Mechanistic pathway.
Scheme 71: C–H functionalization reaction of enamines to produce diversified heterocycles.
Scheme 72: A plausible mechanism.
Scheme 73: CuI-promoted aerobic oxidative cyclization reaction of ketoxime acetates and pyridines.
Scheme 74: CuI-catalyzed pathway for the formation of imidazo[1,2-a]pyridine.
Scheme 75: Mechanistic pathway.
Scheme 76: Mechanistic rationale for the synthesis of products.
Scheme 77: Copper-catalyzed synthesis of vinyloxy-IP.
Scheme 78: Regioselective product formation with propiolates.
Scheme 79: Proposed mechanism for vinyloxy-IP formation.
Scheme 80: Regioselective synthesis of 3-hetero-substituted imidazo[1,2-a]pyridines with different reaction su...
Scheme 81: Mechanistic pathway.
Scheme 82: CuI-mediated synthesis of 3-formylimidazo[1,2-a]pyridines.
Scheme 83: Radical pathway for 3-formylated IP synthesis.
Scheme 84: Pd-catalyzed urea-cyclization reaction for IPs.
Scheme 85: Pd-catalyzed one-pot-tandem amination and intramolecular amidation reaction.
Figure 5: Scope of aniline nucleophiles.
Scheme 86: Pd–Cu-catalyzed Sonogashira coupling reaction.
Scheme 87: One-pot amide coupling reaction for the synthesis of imidazo[4,5-b]pyridines.
Scheme 88: Urea cyclization reaction for the synthesis of two series of pyridines.
Scheme 89: Amidation reaction for the synthesis of imidazo[4,5-b]pyridines.
Figure 6: Amide scope.
Scheme 90: Pd NPs-catalyzed 3-component reaction for the synthesis of 2,3-diarylated IPs.
Scheme 91: Plausible mechanistic pathway for Pd NPs-catalyzed MCR.
Scheme 92: Synthesis of chromenoannulated imidazo[1,2-a]pyridines.
Scheme 93: Mechanism for the synthesis of chromeno-annulated IPs.
Scheme 94: Zinc oxide NRs-catalyzed synthesis of imidazo[1,2-a]azines/diazines.
Scheme 95: Zinc oxide-catalyzed isocyanide based GBB reaction.
Scheme 96: Reaction pathway for ZnO-catalyzed GBB reaction.
Scheme 97: Mechanistic pathway.
Scheme 98: ZnO NRs-catalyzed MCR for the synthesis of imidazo[1,2-a]azines.
Scheme 99: Ugi type GBB three-component reaction.
Scheme 100: Magnetic NPs-catalyzed synthesis of imidazo[1,2-a]pyridines.
Scheme 101: Regioselective synthesis of 2-alkoxyimidazo[1,2-a]pyridines catalyzed by Fe-SBA-15.
Scheme 102: Plausible mechanistic pathway for the synthesis of 2-alkoxyimidazopyridine.
Scheme 103: Iron-catalyzed synthetic approach.
Scheme 104: Iron-catalyzed aminooxygenation reaction.
Scheme 105: Mechanistic pathway.
Scheme 106: Rh(III)-catalyzed double C–H activation of 2-substituted imidazoles and alkynes.
Scheme 107: Plausible reaction mechanism.
Scheme 108: Rh(III)-catalyzed non-aromatic C(sp2)–H bond activation–functionalization for the synthesis of imid...
Scheme 109: Reactivity and selectivity of different substrates.
Scheme 110: Rh-catalyzed direct C–H alkynylation by Li et al.
Scheme 111: Suggested radical mechanism.
Scheme 112: Scandium(III)triflate-catalyzed one-pot reaction and its mechanism for the synthesis of benzimidazo...
Scheme 113: RuCl3-assisted Ugi-type Groebke–Blackburn condensation reaction.
Scheme 114: C-3 aroylation via Ru-catalyzed two-component reaction.
Scheme 115: Regioselective synthetic mechanism.
Scheme 116: La(III)-catalyzed one-pot GBB reaction.
Scheme 117: Mechanistic approach for the synthesis of imidazo[1,2-a]pyridines.
Scheme 118: Synthesis of imidazo[1,2-a]pyridine using LaMnO3 NPs under neat conditions.
Scheme 119: Mechanistic approach.
Scheme 120: One-pot 3-CR for regioselective synthesis of 2-alkoxy-3-arylimidazo[1,2-a]pyridines.
Scheme 121: Formation of two possible products under optimization of the catalysts.
Scheme 122: Mechanistic strategy for NiFe2O4-catalyzed reaction.
Scheme 123: Two-component reaction for synthesizing imidazodipyridiniums.
Scheme 124: Mechanistic scheme for the synthesis of imidazodipyridiniums.
Scheme 125: CuI-catalyzed arylation of imidazo[1,2-a]pyridines.
Scheme 126: Mechanism for arylation reaction.
Scheme 127: Cupric acetate-catalyzed double carbonylation approach.
Scheme 128: Radical mechanism for double carbonylation of IP.
Scheme 129: C–S bond formation reaction catalyzed by cupric acetate.
Scheme 130: Cupric acetate-catalyzed C-3 formylation approach.
Scheme 131: Control experiments for signifying the role of DMSO and oxygen.
Scheme 132: Mechanism pathway.
Scheme 133: Copper bromide-catalyzed CDC reaction.
Scheme 134: Extension of the substrate scope.
Scheme 135: Plausible radical pathway.
Scheme 136: Transannulation reaction for the synthesis of imidazo[1,5-a]pyridines.
Scheme 137: Plausible reaction pathway for denitrogenative transannulation.
Scheme 138: Cupric acetate-catalyzed C-3 carbonylation reaction.
Scheme 139: Plausible mechanism for regioselective C-3 carbonylation.
Scheme 140: Alkynylation reaction at C-2 of 3H-imidazo[4,5-b]pyridines.
Scheme 141: Two-way mechanism for C-2 alkynylation of 3H-imidazo[4,5-b]pyridines.
Scheme 142: Palladium-catalyzed SCCR approach.
Scheme 143: Palladium-catalyzed Suzuki coupling reaction.
Scheme 144: Reaction mechanism.
Scheme 145: A phosphine free palladium-catalyzed synthesis of C-3 arylated imidazopyridines.
Scheme 146: Palladium-mediated Buchwald–Hartwig cross-coupling reaction.
Figure 7: Structure of the ligands optimized.
Scheme 147: Palladium acetate-catalyzed direct arylation of imidazo[1,2-a]pyridines.
Scheme 148: Palladium acetate-catalyzed mechanistic pathway.
Scheme 149: Palladium acetate-catalyzed regioselective arylation reported by Liu and Zhan.
Scheme 150: Mechanism for selective C-3 arylation of IP.
Scheme 151: Pd(II)-catalyzed alkenylation reaction with styrenes.
Scheme 152: Pd(II)-catalyzed alkenylation reaction with acrylates.
Scheme 153: A two way mechanism.
Scheme 154: Double C–H activation reaction catalyzed by Pd(OAc)2.
Scheme 155: Probable mechanism.
Scheme 156: Palladium-catalyzed decarboxylative coupling.
Scheme 157: Mechanistic cycle for decarboxylative arylation reaction.
Scheme 158: Ligand-free approach for arylation of imidazo[1,2-a]pyridine-3-carboxylic acids.
Scheme 159: Mechanism for ligandless arylation reaction.
Scheme 160: NHC-Pd(II) complex assisted arylation reaction.
Scheme 161: C-3 arylation of imidazo[1,2-a]pyridines with aryl bromides catalyzed by Pd(OAc)2.
Scheme 162: Pd(II)-catalyzed C-3 arylations with aryl tosylates and mesylates.
Scheme 163: CDC reaction for the synthesis of imidazo[1,2-a]pyridines.
Scheme 164: Plausible reaction mechanism for Pd(OAc)2-catalyzed synthesis of imidazo[1,2-a]pyridines.
Scheme 165: Pd-catalyzed C–H amination reaction.
Scheme 166: Mechanism for C–H amination reaction.
Scheme 167: One-pot synthesis for 3,6-di- or 2,3,6-tri(hetero)arylimidazo[1,2-a]pyridines.
Scheme 168: C–H/C–H cross-coupling reaction of IPs and azoles catalyzed by Pd(II).
Scheme 169: Mechanistic cycle.
Scheme 170: Rh-catalyzed C–H arylation reaction.
Scheme 171: Mechanistic pathway for C–H arylation of imidazo[1,2-a]pyridine.
Scheme 172: Rh(III)-catalyzed double C–H activation of 2-phenylimidazo[1,2-a]pyridines and alkynes.
Scheme 173: Rh(III)-catalyzed mechanistic pathway.
Scheme 174: Rh(III)-mediated oxidative coupling reaction.
Scheme 175: Reactions showing functionalization of the product obtained by the group of Kotla.
Scheme 176: Mechanism for Rh(III)-catalyzed oxidative coupling reaction.
Scheme 177: Rh(III)-catalyzed C–H activation reaction.
Scheme 178: Mechanistic cycle.
Scheme 179: Annulation reactions of 2-arylimidazo[1,2-a]pyridines and alkynes.
Scheme 180: Two-way reaction mechanism for annulations reaction.
Scheme 181: [RuCl2(p-cymene)]2-catalyzed C–C bond formation reaction.
Scheme 182: Reported reaction mechanism.
Scheme 183: Fe(III) catalyzed C-3 formylation approach.
Scheme 184: SET mechanism-catalyzed by Fe(III).
Scheme 185: Ni(dpp)Cl2-catalyzed KTC coupling.
Scheme 186: Pd-catalyzed SM coupling.
Scheme 187: Vanadium-catalyzed coupling of IP and NMO.
Scheme 188: Mechanistic cycle.
Scheme 189: Selective C3/C5–H bond functionalizations by mono and bimetallic systems.
Scheme 190: rGO-Ni@Pd-catalyzed C–H bond arylation of imidazo[1,2-a]pyridine.
Scheme 191: Mechanistic pathway for heterogeneously catalyzed arylation reaction.
Scheme 192: Zinc triflate-catalyzed coupling reaction of substituted propargyl alcohols.
Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes
- Ruben Pomar Fuentespina,
- José Angel Garcia de la Cruz,
- Gabriel Durin,
- Victor Mamane,
- Jean-Marc Weibel and
- Patrick Pale
Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141
- Shimizu [6][7], and our experience on the metalation of alkynyloxiranes and reactivity studies of the so-formed alkynyloxirane anions [12][13], we explored the reaction of such anions with various boron derivatives in order to produce stereodefined α-enynes after Matteson-type rearrangement [14] and
- challenge in organic chemistry. Results and Discussion Reaction set up First we selected the simple 2-ethynyl-3-dimethyloxirane 1a to probe the feasibility of the reaction. In order to avoid unwanted reactions upon metalation [23], the ethynyl group was silylated and a bulky silyl group was installed to
- occurred upon oxygen-directed metalation. The resulting oxiranyllithium probably exists as a dimer in solution, as it has been nicely evidenced by structural characterization and NMR studies of the lithiated o-trifluoromethylstyrene oxide [37]. Such dimerization obviously stabilizes the oxiranyllithium
Graphical Abstract
Scheme 1: Stereospecific formation of α-enynes from alkynyloxiranes.
Scheme 2: Trapping experiments of the oxiranyllithium derived from cis or trans-alkynyloxiranes 1b, and their...
Scheme 3: Proposed mechanism for the rearrangement of alkynyloxiranes to α-enynes through metalation and bory...
Extending mechanochemical porphyrin synthesis to bulkier aromatics: tetramesitylporphyrin
- Qiwen Su and
- Tamara D. Hamilton
Beilstein J. Org. Chem. 2019, 15, 1149–1153, doi:10.3762/bjoc.15.111
- mechanochemical synthesis is carried out at room temperature with no added solvent during the condensation step, simplifying and reducing the environmental impact for the synthesis of this important class of molecules. Notably, James et al. have reported the simple and clean mechanochemical metalation of
Graphical Abstract
Figure 1: A) Porphyrin structure and labelling system. B) Substituents in the ortho-position of the group att...
Scheme 1: Steps leading to the formation of a porphyrin.
Scheme 2: Mechanochemical synthesis of tetramesitylporphyrin.
Design, synthesis and spectroscopic properties of crown ether-capped dibenzotetraaza[14]annulenes
- Krzysztof M. Zwoliński and
- Julita Eilmes
Beilstein J. Org. Chem. 2019, 15, 617–622, doi:10.3762/bjoc.15.57
- satisfactory 26–28% isolated yields and fully characterized based on HR-ESIMS, FTIR-ATR, 1H and 13C NMR spectroscopy and elemental analysis. These novel receptors are expected to bind both the transition, alkali and alkaline-earth metals, and also, after DBTAA subunit metalation the whole ion pairs. The
Graphical Abstract
Figure 1: Timeline for the structure evolution of crown-capped DBTAAs (created on the basis of references [24-28]).
Scheme 1: Synthesis of the crown-capped DBTAA receptors 3a and 3b. Reagents and conditions: i) Et3N, CH3CN, r...
Figure 2: 1H NMR spectra (298 K, CDCl3) of: a) crown ether-capped receptor 3b and b) it’s corresponding paren...
Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS
- Sven Thierbach,
- Max Wienhold,
- Susanne Fetzner and
- Ulrich Hennecke
Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18
- PQS such as formylation followed by oxidation failed when applied to OMe-HHQ (3). Alternatively, ortho-metalation next to the methoxy group of OMe-HHQ (3) followed by borylation/oxidation was investigated. Several trials using different lithium bases failed and only small amounts of oxidation products
- in the benzylic position could be observed. Instead of direct ortho-metalation, a strategy based on halogen–lithium exchange proved to be more suitable. To this end, HHQ (1) was converted into 3I-HHQ (8) following a literature procedure [21]. 3I-HHQ (8) was then methylated using the MeI/K2CO3
Graphical Abstract
Scheme 1: Methylation of HHQ (1).
Scheme 2: Synthesis of methylated HQNO derivatives.
Scheme 3: Synthesis of methylated PQS derivatives.
Figure 1: Overview of AQ compounds (A), and effect of AQs on the growth of S. aureus Newman (B). 24-Well plat...
Figure 2: Inhibition of cellular O2 consumption rate (cOCR) of S. aureus Newman. Cell suspensions (OD600 nm o...
Figure 3: Impact on AQ quorum sensing by the newly synthesized AQ derivatives. Cultures of P. aeruginosa PAO1...
Hydroarylations by cobalt-catalyzed C–H activation
- Rajagopal Santhoshkumar and
- Chien-Hong Cheng
Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202
- conditions and inexpensive catalyst. The reaction proceeds through an amide-assisted C–H metalation followed by alkyne insertion and protonation [54]. The reaction also acknowledged that the Co(III) species possess unique nucleophilic reactivity compared with the Rh(III) species for the annulation reaction
Graphical Abstract
Scheme 1: Cobalt-catalyzed C–H carbonylation.
Scheme 2: Hydroarylation by C–H activation.
Scheme 3: Pathways for cobalt-catalyzed hydroarylations.
Scheme 4: Co-catalyzed hydroarylation of alkynes with azobenzenes.
Scheme 5: Co-catalyzed hydroarylation of alkynes with 2-arylpyridines.
Scheme 6: Co-catalyzed addition of azoles to alkynes.
Scheme 7: Co-catalyzed addition of indoles to alkynes.
Scheme 8: Co-catalyzed hydroarylation of alkynes with imines.
Scheme 9: A plausible pathway for Co-catalyzed hydroarylation of alkynes.
Scheme 10: Co-catalyzed anti-selective C–H addition to alkynes.
Scheme 11: Co(III)-catalyzed hydroarylation of alkynes with indoles.
Scheme 12: Co(III)-catalyzed branch-selective hydroarylation of alkynes.
Scheme 13: Co(III)-catalyzed hydroarylation of terminal alkynes with arenes.
Scheme 14: Co(III)-catalyzed hydroarylation of alkynes with amides.
Scheme 15: Co(III)-catalyzed C–H alkenylation of arenes.
Scheme 16: Co-catalyzed alkylation of substituted benzamides with alkenes.
Scheme 17: Co-catalyzed switchable hydroarylation of styrenes with 2-aryl pyridines.
Scheme 18: Co-catalyzed linear-selective hydroarylation of alkenes with imines.
Scheme 19: Co-catalyzed linearly-selective hydroarylation of alkenes with N–H imines.
Scheme 20: Co-catalyzed branched-selective hydroarylation of alkenes with imines.
Scheme 21: Mechanism of Co-catalyzed hydroarylation of alkenes.
Scheme 22: Co-catalyzed intramolecular hydroarylation of indoles.
Scheme 23: Co-catalyzed asymmetric hydroarylation of alkenes with indoles.
Scheme 24: Co-catalyzed hydroarylation of alkenes with heteroarenes.
Scheme 25: Co(III)-catalyzed hydroarylation of activated alkenes with 2-phenyl pyridines.
Scheme 26: Co(III)-catalyzed C–H alkylation of arenes.
Scheme 27: Co(III)-catalyzed C2-alkylation of indoles.
Scheme 28: Co(III)-catalyzed switchable hydroarylation of alkyl alkenes with indoles.
Scheme 29: Co(III)-catalyzed C2-allylation of indoles.
Scheme 30: Co(III)-catalyzed ortho C–H alkylation of arenes with maleimides.
Scheme 31: Co(III)-catalyzed hydroarylation of maleimides with arenes.
Scheme 32: Co(III)-catalyzed hydroarylation of allenes with arenes.
Scheme 33: Co-catalyzed hydroarylative cyclization of enynes with carbonyl compounds.
Scheme 34: Mechanism for the Co-catalyzed hydroarylative cyclization of enynes with carbonyl compounds.
Scheme 35: Co-catalyzed addition of 2-arylpyridines to aromatic aldimines.
Scheme 36: Co-catalyzed addition of 2-arylpyridines to aziridines.
Scheme 37: Co(III)-catalyzed hydroarylation of imines with arenes.
Scheme 38: Co(III)-catalyzed addition of arenes to ketenimines.
Scheme 39: Co(III)-catalyzed three-component coupling.
Scheme 40: Co(III)-catalyzed hydroarylation of aldehydes.
Scheme 41: Co(III)-catalyzed addition of arenes to isocyanates.
Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives
- Jiao-Na Han,
- Cong Du,
- Xinju Zhu,
- Zheng-Long Wang,
- Yue Zhu,
- Zhao-Yang Chu,
- Jun-Long Niu and
- Mao-Ping Song
Beilstein J. Org. Chem. 2018, 14, 2090–2097, doi:10.3762/bjoc.14.183
- calculations (DFT) [30][31], the C–H activation most possibly proceeded via a single-electron transfer (SET) path compared to a concerted metalation-deprotonation (CMD) path. Followed by an intermolecular SET process, the cation-radical intermediate A was generated, which coordinates with a CoIII species to
Graphical Abstract
Figure 1: Strategies for cobalt-catalyzed alkoxylation.
Scheme 1: Reaction scope with respect to N-(naphthalen-1-yl)picolinamide derivatives. Reaction conditions: 1 ...
Scheme 2: Reaction scope with respect to alcohols. Reaction conditions: 1a (0.2 mmol), 2 (1.0 mL), CoF2 (20 m...
Scheme 3: Control experiments and mechanistic studies.
Scheme 4: Proposed reaction mechanism.
Scheme 5: Removal of the directing group.
Cobalt-catalyzed C–H cyanations: Insights into the reaction mechanism and the role of London dispersion
- Eric Detmar,
- Valentin Müller,
- Daniel Zell,
- Lutz Ackermann and
- Martin Breugst
Beilstein J. Org. Chem. 2018, 14, 1537–1545, doi:10.3762/bjoc.14.130
- experimental data indicated a reversible C–H metalation, which led to the suggested catalytic cycle of Scheme 2 [30]. As computational investigations also allow the study of intermediates that are too unstable to be observed under the experimental conditions, we have analyzed the underlying reaction mechanism
- agreement with the experimental findings: The calculated high barriers match the prolonged reaction times and high temperature required in the experimental studies and the reversible C–H metalation [30]. Influence of London dispersion In recent years, London dispersion, the attractive part of the van-der
Graphical Abstract
Scheme 1: Cycloaddition reaction of in situ generated benzynes resulting in the sterically more hindered addu...
Scheme 2: Recently developed cobalt-catalyzed C–H cyanation [30].
Figure 1: Calculated free-energy profile for the cobalt-catalyzed C–H cyanation of 2-phenylpyridine (1a) [in ...
Figure 2: Calculated structures, selected bond lengths (in Å), and imaginary frequencies for representative i...
Scheme 3: Kinetic profile of the cobalt-catalyzed C–H cyanation with differently substituted cyanating agents ...
Figure 3: Noncovalent interaction (NCI) analysis for selected intermediates and transition states. The gradie...
Figure 4: Projected dispersion interaction density (DID) plots for selected intermediates and transition stat...
Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials
- Alberto Spinella,
- Marco Russo,
- Antonella Di Vincenzo,
- Delia Chillura Martino and
- Paolo Lo Meo
Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127
- acquired on a FEG-SEM FEI versa 3D microscope. The acceleration voltage was 10 kV. Tiny amounts of powdered samples were dispersed in ethanol. Two drops were deposited on the stub and let evaporating. Micrographs were directly acquired without metalation. DSC determinations were performed on a DSC Q200
Graphical Abstract
Scheme 1: Structures of: a) calixarene Ca-OP; b) alkyl diazides A1–A4.
Scheme 2: Structures of p-nitroaniline derivatives 1–5 and dyes 6–10.
Figure 1: FTIR spectra of Ca-OP (red), A2 (green) and CaNS2 (blue).
Figure 2: a) 13C{1H} CP-MAS NMR spectra of CaNSs; b) signal attributions.
Figure 3: Selection of SEM micrographs for materials for CaNS1 (a), CaNS2 (b), CaNS3 (c) and CaNS4 (d).
Polysubstituted ferrocenes as tunable redox mediators
- Sven D. Waniek,
- Jan Klett,
- Christoph Förster and
- Katja Heinze
Beilstein J. Org. Chem. 2018, 14, 1004–1015, doi:10.3762/bjoc.14.86
- application as redox mediator (Scheme 2) [55][56]. Ferrocenyl esters 1–4 are synthetically accessible via the acids of 1 [45][46], 2 [57], 3 and 4 [54] in a direct selective metalation of ferrocene [54][57][58][59][60], quenching with carbon dioxide, followed by esterification [45][46][47][48][54]. The 1,1
Graphical Abstract
Scheme 1: Selected transformations with ferrocene/ferrocenium as SET reagents (a) [27], catalyzed (b,c) [29-31] and medi...
Scheme 2: Methyl esters of ferrocene carboxylic acids 1 [45,46], 2 [47-49], 2a [50], 2b [51,52], 3, 4 [54] and pseudo octahedral high-spin...
Figure 1: Normalized cyclic voltammograms for anodic sweeps of 1–4 in CH2Cl2/[n-Bu4N][B(C6F5)4] (scan rate 10...
Figure 2: Electrochemical potentials E1/2 (vs FcH/FcH+) of esters 1–4 versus sum of Hammett values ∑σp/m with...
Figure 3: a) Partial ATR IR spectra (transmission normalized, C=O stretching vibration region) of solids 1–4....
Figure 4: IR spectroelectrochemical oxidation of 3 to 3+ in CH2Cl2/[n-Bu4N][B(C6F5)4] (C=O stretching vibrati...
Figure 5: a) Normalized UV–vis spectra of 1–4 in CH2Cl2. b) Normalized UV–vis absorptions of 1+–4+ in CH2Cl2/[...
Figure 6: Absorption energy E of ferrocene bands of 1–4 (a) and energies of the low energy absorption maxima ...
Figure 7: UV–vis spectroelectrochemical oxidation of 3 in CH2Cl2/[n-Bu4N][B(C6F5)4] (0–1.1 V vs Ag pseudo ref...
Figure 8: 1H NMR oxidation titration of 3 in CD2Cl2 with [N(2,4-C6H3Br2)3]+ as oxidant. a[N(2,4-C6H3Br2)3]. b...
Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline
- Benedikt C. Melzer,
- Jan G. Felber and
- Franz Bracher
Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8
- products and in drug development and hence, effective synthetic approaches are required. Here we present a novel method for the introduction of a methyl group at C1 of isoquinolines. This is exemplified by a new total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline. Direct metalation of
- , after quaternization with iodomethane, is easily converted into the desired 1-methylisoquinoline by hydrogenolysis of both the benzylamine and benzyl ether groups. Keywords: alkaloid; aminomethylation; hydrogenolysis; isoquinoline; metalation; methylation; Introduction The isoquinoline ring system has
- methods have been published over the decades for the construction of highly substituted isoquinolines [4]. Alternatively, subsequent functionalization of isoquinolines is feasible, e.g., via Pd-catalyzed C–H functionalization [5] or regioselective direct ring metalation (at C1) [6][7][8]. General aspects
Graphical Abstract
Figure 1: Previously published total syntheses of alkaloid 1 [11,12].
Scheme 1: Total synthesis of alkaloid 1 via direct ring metalation and methylation.
Scheme 2: Total synthesis of alkaloid 1 via the aminomethyl intermediate 5 and selectivity’s found in debenzy...
