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Search for "nitrogen heterocycles" in Full Text gives 77 result(s) in Beilstein Journal of Organic Chemistry.
Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate
- Mysore Bhyrappa Harisha,
- Pandi Dhanalakshmi,
- Rajendran Suresh,
- Raju Ranjith Kumar and
- Shanmugam Muthusubramanian
Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178
- precursor for nitrogen heterocycles. As a part of our synthetic design towards the construction of five-membered heterocycles, we have previously reported the synthesis of highly substituted imidazoles [6], indoles [7] and pyrroles [8] starting from different azidochalcones. In continuation, employing α
Graphical Abstract
Figure 1: Examples of biologically active oxazole and aminothiazole scaffolds.
Scheme 1: Strategies for the synthesis of 2,4,5-trisubstituted oxazole from azirine. a) I2, PPh3; b) NaH, 1H-...
Scheme 2: Scope of the α-azidochalcones. The reactions were carried out at reflux temperature, using 1 (1 mmo...
Scheme 3: Large-scale synthesis of 3i.
Figure 2: Large-scale synthesis of 3i. a) At the start of the reaction, b) after the reaction.
Scheme 4: Acetyl derivative of 3d.
Figure 3: ORTEP diagram of compound 5.
Scheme 5: Synthesis of S-methyl/benzylated products 6 and 7.
Scheme 6: Control experiments.
Scheme 7: Plausible mechanism proposed for the formation of 2,4,5-trisubstituted oxazoles 3.
Scheme 8: Reaction of vinyl azide 1 and 3 with ferric nitrate. Reactions were carried out at reflux temperatu...
Figure 4: X-ray crystal structure of 4h.
Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation
- Kumar Godugu,
- Venkata Divya Sri Yadala,
- Mohammad Khaja Mohinuddin Pinjari,
- Trivikram Reddy Gundala,
- Lakshmi Reddy Sanapareddy and
- Chinna Gangi Reddy Nallagondu
Beilstein J. Org. Chem. 2020, 16, 1881–1900, doi:10.3762/bjoc.16.156
- : benzimidazoles; dihydropyrimidinones; highly substituted pyridines; natural dolomitic limestone; ultrasound irradiation; Introduction Nitrogen heterocycles are recognized as “privileged medicinal scaffolds” because these compounds are found in a wide variety of bioactive natural products and pharmaceuticals [1
Graphical Abstract
Figure 1: The benzimidazoles I–IV, dihydropyrimidinones/-thiones V–VIII, and 2-amino-4-aryl-3,5-dicarbonitril...
Scheme 1: NDL-catalyzed synthesis of i) 1,2-disubstituted benzimidazoles 3, ii) dihydropyrimidinones/-thiones ...
Figure 2: XRD pattern of the NDL catalyst.
Figure 3: FTIR spectrum of the NDL catalyst.
Figure 4: Raman spectrum of the NDL catalyst.
Figure 5: SEM images of the NDL catalyst.
Figure 6: EDAX analysis of the NDL catalyst.
Scheme 2: Unexpected formation of the bisimine I, 3h, from o-phenylenediamine (1) and salicylaldehyde (2h).
Figure 7: 1H NMR spectrum of 2,2'-((1E,1'E)-(1,2-phenylenebis(azanylylidene))bis (methanylylidene))diphenol (...
Figure 8: XRD pattern of a) the fresh NDL catalyst; b) the recovered NDL catalyst after the 7th cycle of the ...
One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions
- Gui-Feng Kang and
- Gang Zhang
Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120
- structures of 1,3,5-triazine-2,4-dithione derivatives were characterized by spectroscopic techniques as well as by single crystal X-ray diffraction. Keywords: aldehydes; multicomponent reactions; nitrogen heterocycles; thiourea; triazinethiones; Introduction The construction of nitrogen-containing
Graphical Abstract
Figure 1: Selected examples of triazinethione-containing bioactive compounds.
Scheme 1: Strategies for the synthesis of triazinethiones.
Scheme 2: Aldehyde substrate scope of three-component reaction of aldehydes, thiourea and trimethyl orthoform...
Scheme 3: Orthoformate substrate scope of the three component reaction of benzaldehyde, thiourea, and orthofo...
Scheme 4: Gram-scale synthesis of 6aa.
Figure 2: X-ray structure of 6-(methylthio)-4-phenyl-3,4-dihydro-1,3,5-triazine-2(1H)-thione (6aa) with therm...
Scheme 5: Control experiments for investigation of the mechanism.
Scheme 6: Plausible mechanism.
Microwave-assisted efficient and facile synthesis of tetramic acid derivatives via a one-pot post-Ugi cascade reaction
- Yong Li,
- Zheng Huang,
- Jia Xu,
- Yong Ding,
- Dian-Yong Tang,
- Jie Lei,
- Hong-yu Li,
- Zhong-Zhu Chen and
- Zhi-Gang Xu
Beilstein J. Org. Chem. 2020, 16, 663–669, doi:10.3762/bjoc.16.63
- has the potential to produce a large number of tetramic acid analogues, which cannot be easily accessed by the classic synthetic methods. Keywords: Dieckmann cyclization; multicomponent reactions; nitrogen heterocycles; one-pot reaction; Ugi reaction; Introduction Nitrogen-containing heterocycles
Graphical Abstract
Figure 1: Structures of natural tetramic acid derivatives with more clinical relevance.
Scheme 1: Synthetic strategy of compound 7a.
Scheme 2: Scope of the Ugi/Dieckmann cyclization reaction route to lead to pyrrolopyridinones 7a–l. aYield of...
Scheme 3: Postulated reaction mechanism.
Rapid, two-pot procedure for the synthesis of dihydropyridinones; total synthesis of aza-goniothalamin
- Thomas J. Cogswell,
- Craig S. Donald and
- Rodolfo Marquez
Beilstein J. Org. Chem. 2020, 16, 135–139, doi:10.3762/bjoc.16.15
- produce the target dihydropyridinones efficiently and in high yields. Keywords: amidoallylation; aza-goniothalamin; dihydropyridinones; protecting-group-free; ring-closing metathesis; two-pot procedure; Introduction Six-membered nitrogen heterocycles are prevalent in many naturally occurring and
- precursor in a single step. This general strategy towards nitrogen heterocycles has been utilized in several reports [20][21][22][23], including asymmetric variants [24][25], but in these cases the ring-closing metathesis precursor was always generated in multiple steps. In order to test this hypothesis
Graphical Abstract
Figure 1: Aza-goniothalamin 1, (R)-(+)-goniothalamin 2 and acylated aza-goniothalamin analogue 3 [14-18].
Scheme 1: One pot synthesis of benzyl carbamate 4 reported by Veenstra and co-workers [19].
Scheme 2: Formation of diene 5 in 66% through a one pot, three component coupling.
Scheme 3: Optimized conditions for the synthesis of diene 5.
Scheme 4: Ring-closing metathesis reaction of diene 5 to yield dihydropyridone 7 [20-23].
Figure 2: Extension of the two-pot methodology to include a variety of different aldehyde starting materials.
Scheme 5: Total synthesis of aza-goniothalamin 1.
Facile regiodivergent synthesis of spiro pyrrole-substituted pseudothiohydantoins and thiohydantoins via reaction of [e]-fused 1H-pyrrole-2,3-diones with thiourea
- Aleksandr I. Kobelev,
- Nikita A. Tretyakov,
- Ekaterina E. Stepanova,
- Maksim V. Dmitriev,
- Michael Rubin and
- Andrey N. Maslivets
Beilstein J. Org. Chem. 2019, 15, 2864–2871, doi:10.3762/bjoc.15.280
- good yields, and the products were isolated without applying preparative chromatography methods. Keywords: diversity-oriented synthesis; hydantoin; nitrogen heterocycles; rearrangement; thiourea; Introduction Hydantoin (imidazolidine-2,4-dione) derivatives are omnipresent among biologically active
Graphical Abstract
Figure 1: Hydantoin-based commercially available drugs.
Scheme 1: Pseudothiohydantoin–thiohydantoin rearrangement.
Scheme 2: Syntheses of regioisomeric 5-spiro-substituted thiohydantoins and pseudothiohydantoins: previous [10] a...
Figure 2: Electrophilic centers of FPDs 1, starting materials of this study.
Scheme 3: Cyclocondensation of FPDs 1 with 1,3-binucleophilic reagents, resulting in pyrrole-2-one-bearing sp...
Scheme 4: Reaction of FPD 1a with thiourea.
Scheme 5: PTR of 3a to 2a.
Scheme 6: Pathways for the formation of compound 2a.
Scheme 7: Reaction of FPD 1a with monosubstituted thioureas.
Scheme 8: Reaction of FPDs 1 with 1,3-dibutylthiourea at room temperature.
Scheme 9: Plausible PTR pathways.
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.
Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization
- Aleksandr S. Krylov,
- Artem A. Petrosian,
- Julia L. Piterskaya,
- Nataly I. Svintsitskaya and
- Albina V. Dogadina
Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159
- synthesized in a similar manner. The presence of a NO2 group in the starting hydrazinylpyridine induces a Dimroth-type rearrangement leading to 2-methylphosphonylated [1,2,4]triazolo[1,5-a]pyridines. Keywords: cyclization; fused-ring systems; nitrogen heterocycles; phosphorylation; rearrangement
Graphical Abstract
Scheme 1: Synthetic approaches to [1,2,4]triazolo[4,3-a]pyridines.
Scheme 2: Synthesis of 3-methylphosphonylated [1,2,4]triazolo[4,3-a]pyridines. Reaction conditions: 1 (1 mmol...
Scheme 3: Synthesis of methylphosphonylated 6(8)-nitro-[1,2,4]triazolo[4,3-a]pyridines and 6(8)-nitro-[1,2,4]...
Scheme 4: Acid-promoted Dimroth rearrangement pathway.
Scheme 5: Synthesis of phosphonylated [1,2,4]triazolo[4,3-a]quinolines and [1,2,4]triazolo[3,4-a]isoquinoline...
Scheme 6: Plausible reaction pathway.
Steroid diversification by multicomponent reactions
- Leslie Reguera,
- Cecilia I. Attorresi,
- Javier A. Ramírez and
- Daniel G. Rivera
Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121
- the steroidal nucleus, the assembly of nitrogen-heterocycles fused to the steroid-ring system, the steroid conjugation and macrocyclization, all relying on MCRs. 2 Modification of the steroidal nucleus and the side chain 2.1 Isocyanide-based MCRs 2.1.1 Steroids as carbonyl component: One of the first
- , Boruah’s group has been very active in the synthesis of nitrogen heterocycles such as pyrimidines, pyrazolopyrimidines and disubstituted pyridines fused to rings A and D of steroids [47][48][49]. Thus far, most applications of MCRs in steroid derivatization aimed at producing derivatives for screening
Graphical Abstract
Figure 1: Structures of natural steroids of A) animal and B) plant origin.
Scheme 1: Synthesis of a steroidal β-lactam by Ugi reaction of a cholanic aldehyde [14].
Scheme 2: Synthetic route to steroidal 2,5-diketopiperazines based on a diastereoselective Ugi-4CR with an an...
Scheme 3: Multicomponent synthesis of a heterocycle–steroid hybrid using a ketosteroid as carbonyl component [18]....
Scheme 4: Synthesis of peptidomimetic–steroid hybrids using the Ugi-4CR with spirostanic amines and carboxyli...
Scheme 5: Synthesis of azasteroids using the Ugi-4CR with androstanic and pregnanic carboxylic acids [22].
Figure 2: Ugi-4CR-derived library of androstanic azasteroids with diverse substitution patterns at the phenyl...
Scheme 6: Synthesis of 4-azacholestanes by an intramolecular Ugi-4C-3R [26].
Scheme 7: Synthesis of amino acid–steroid hybrid by multiple Ugi-4CR using steroidal isocyanides [29].
Scheme 8: Synthesis of ecdysteroid derivatives by Ugi-4CR using a steroidal isocyanide [30].
Scheme 9: Stereoselective multicomponent synthesis of a steroid–tetrahydropyridine hybrid using a chiral bifu...
Scheme 10: Pd(II)-catalyzed three-component reaction with an alkynyl seco-cholestane [34].
Scheme 11: Multicomponent synthesis of steroid–thiazole hybrids from a steroidal ketone [36].
Scheme 12: Synthesis of cholanic pseudo-peptide derivatives by novel MCRs based on the reactivity of ynamide [37,38].
Scheme 13: Synthesis of steroid-fused pyrimidines and pyrimidones using the Biginelli-3CR [39,42,43].
Scheme 14: Synthesis of steroidal pyridopyrimidines by a reaction sequence comprising a 4CR followed by a post...
Scheme 15: Synthesis of steroid-fused pyrimidines by MCR of 2-hydroxymethylene-3-ketosteroids [46].
Scheme 16: Synthesis of steroid-fused naphthoquinolines by the Kozlov–Wang MCR using ketosteroids [50,51].
Scheme 17: Conjugation of steroids to carbohydrates and peptides by the Ugi-4CR [62,63].
Scheme 18: Solid-phase multicomponent conjugation of peptides to steroids by the Ugi-4CR [64].
Scheme 19: Solid-phase multicomponent conjugation of peptides to steroids by the Petasis-3CR [68].
Scheme 20: Synthesis of steroidal macrobicycles (cages) by multiple multicomponent macrocyclizations based on ...
Scheme 21: One-pot synthesis of steroidal cages by double Ugi-4CR-based macrocyclizations [76].
Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins
- Aleksandr I. Kobelev,
- Ekaterina E. Stepanova,
- Maksim V. Dmitriev and
- Andrey N. Maslivets
Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32
- developed via an unprecedented annulation of pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones by thioacetamide. A new way of C–H functionalization of thioacetamide has been discovered. The reaction proceeds under green catalyst-free conditions. Keywords: annulation; domino reactions; isatin; nitrogen
- heterocycles; thioamides; Introduction Omnipresent among natural compounds and drugs, the indole core is a privileged scaffold for library design and drug discovery [1]. Its dioxo derivative, isatin (1H-indole-2,3-dione), is an important building block for the construction of diverse indole-based compounds
Graphical Abstract
Scheme 1: Approaches to the synthesis of the 5-azaisatin core.
Scheme 2: Our previous work on the interaction of PBTs 2 with thioamides.
Scheme 3: Interaction of PBTs 2 with thioacetamide.
Scheme 4: Plausible pathways for the formation of compound 4.
Scheme 5: Experiments on the intermolecular trapping of spiro[thiazolo-5,2'-pyrrole] 3a.
Scheme 6: Exploration of the substrate scope.
Scheme 7: Interaction of PBT 2a with N-phenylthioacetamide.
One hundred years of benzotropone chemistry
- Arif Dastan,
- Haydar Kilic and
- Nurullah Saracoglu
Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98
- product via double bonds (Scheme 17). Azocine derivatives, eight-membered nitrogen heterocycles, exist as the core structure in many natural and non-natural products [84]. Nevertheless, 2-methyoxyazocine (96) reduces related aromatic 10π-electron dianion 97 (Scheme 18). Paquette’s group investigated benzo
Graphical Abstract
Scheme 1: Tropone (1), tropolone (2) and their resonance structures.
Figure 1: Natural products containing a tropone nucleus.
Figure 2: Possible isomers 11–13 of benzotropone.
Scheme 2: Synthesis of benzotropones 11 and 12.
Scheme 3: Oxidation products of benzotropylium fluoroborate (16).
Scheme 4: Oxidation of 7-bromo-5H-benzo[7]annulene (22).
Scheme 5: Synthesis of 4,5-benzotropone (11) using o-phthalaldehyde (27).
Scheme 6: Synthesis of 4,5-benzotropone (11) starting from oxobenzonorbornadiene 31.
Scheme 7: Acid-catalyzed cleavage of oxo-bridge of 34.
Scheme 8: Synthesis of 4,5-benzotropone (11) from o-xylylene dibromide (38).
Scheme 9: Synthesis of 4,5-benzotropone (11) via the carbene adduct 41.
Scheme 10: Heck coupling strategy for the synthesis of 11.
Scheme 11: Synthesis of benzofulvalenes via carbonyl group of 4,5-benzotropone (11).
Figure 3: Some cycloheptatrienylium cations.
Scheme 12: Synthesis of condensation product 63 and its subsequent oxidative cyclization products.
Figure 4: A novel series of benzo[7]annulenes prepared from 4,5-benzotropone (11).
Scheme 13: Preparation of substituted benzo[7]annulene 72 using the Mukaiyama-Michael reaction.
Figure 5: Possible benzo[7]annulenylidenes 73–75.
Scheme 14: Thermal and photochemical decomposition of 7-diazo-7H-benzo[7]annulene (76) and the trapping of int...
Scheme 15: Synthesis of benzoheptafulvalene 86.
Scheme 16: Synthesis of 7-(diphenylmethylene)-7H-benzo[7]annulene (89).
Scheme 17: Reaction of 4,5-benzotropone (11) with dimethyl diazomethane.
Scheme 18: Synthesis of dihydrobenzomethoxyazocine 103.
Scheme 19: Synthesis and reducibility of benzo-homo-2-methoxyazocines.
Scheme 20: Synthesis of 4,5-benzohomotropones 104 and 115 from 4,5-benzotropones 11 and 113.
Scheme 21: A catalytic deuterogenation of 4,5-benzotropone (11) and synthesis of 5-monosubstituted benzo[7]ann...
Scheme 22: Synthesis of methyl benzo[7]annulenes 131 and 132.
Scheme 23: Ambident reactivity of halobenzo[7]annulenylium cations 133a/b.
Scheme 24: Preparation of benzo[7]annulenylidene–iron complexes 147.
Scheme 25: Synthesis of 1-ethynylbenzotropone (150) and the etheric compound 152 from 4,5-benzotropone (11) wi...
Scheme 26: Thermal decomposition of 4,5-benzotropone (11).
Scheme 27: Reaction of 4,5-benzotropone (11) with 1,2-ethanediol and 1,2-ethanedithiol.
Scheme 28: Conversions of 1-benzosuberone (162) to 2,3-benzotropone (12).
Scheme 29: Synthesis strategies for 2,3-bezotropone (12) using 1-benzosuberones.
Scheme 30: Oxidation-based synthesis of 2,3-benzotropone (12) via 1-benzosuberone (162).
Scheme 31: Synthesis of 2,3-benzotropone (12) from α-tetralone (171) via ring-expansion.
Scheme 32: Preparation of 2,3-benzotropone (12) by using of benzotropolone 174.
Figure 6: Benzoheptafulvenes as condensation products of 2,3-benzotropone (12).
Scheme 33: Conversion of 2,3-benzotropone (12) to tosylhydrazone salt 182 and gem-dichloride 187.
Figure 7: Benzohomoazocines 191–193 and benzoazocines 194–197.
Scheme 34: From 2,3-benzotropone (12) to carbonium ions 198–201.
Scheme 35: Cycloaddition reactions of 2,3-benzotropone (12).
Scheme 36: Reaction of 2,3-benzotropone (12) with various reagents and compounds.
Figure 8: 3,4-Benzotropone (13) and its resonance structure.
Scheme 37: Synthesis of 6,7-benzobicyclo[3.2.0]hepta-3,6-dien-2-one (230).
Figure 9: Photolysis and thermolysis products of 230.
Figure 10: Benzotropolones and their tautomeric structures.
Scheme 38: Synthesis strategies of 4,5-benzotropolone (238).
Scheme 39: Synthesis protocol for 2-hydroxy-4,5-benzotropone (238) using oxazole-benzo[7]annulene 247.
Figure 11: Some quinoxaline and pyrazine derivatives 254–256 prepared from 4,5-benzotropolone (238).
Scheme 40: Nitration product of 4,5-benzotropolone (238) and its isomerization to 1-nitro-naphthoic acid (259)....
Scheme 41: Synthesis protocol for 6-hydroxy-2,3-benzotropone (239) from benzosuberone (162).
Scheme 42: Various reactions via 6-hydroxy-2,3-benzotropone (239).
Scheme 43: Photoreaction of 6-hydroxy-2,3-benzotropone (239).
Scheme 44: Synthesis of 7-hydroxy-2,3-benzotropone (241) from benzosuberone (162).
Scheme 45: Synthesis strategy for 7-hydroxy-2,3-benzotropone (241) from ketone 276.
Scheme 46: Synthesis of 7-hydroxy-2,3-benzotropone (241) from β-naphthoquinone (280).
Scheme 47: Synthesis of 7-hydroxy-2,3-benzotropone (241) from bicyclic endoperoxide 213.
Scheme 48: Synthesis of 7-hydroxy-2,3-benzotropone (241) by ring-closing metathesis.
Figure 12: Various monosubstitution products 289–291 of 7-hydroxy-2,3-benzotropone (241).
Scheme 49: Reaction of 7-hydroxy-2,3-benzotropone (241) with various reagents.
Scheme 50: Synthesis of 4-hydroxy-2,3-benzotropones 174 and 304 from diketones 300/301.
Scheme 51: Catalytic hydrogenation of diketones 300 and 174.
Scheme 52: Synthesis of halo-benzotropones from alkoxy-naphthalenes 306, 307 and 310.
Figure 13: Unexpected byproducts 313–315 during synthesis of chlorobenzotropone 309.
Figure 14: Some halobenzotropones and their cycloadducts.
Scheme 53: Multisep synthesis of 2-chlorobenzotropone 309.
Scheme 54: A multistep synthesis of 2-bromo-benzotropone 26.
Scheme 55: A multistep synthesis of bromo-2,3-benzotropones 311 and 316.
Scheme 56: Oxidation reactions of 8-bromo-5H-benzo[7]annulene (329) with some oxidants.
Scheme 57: Synthesis of 2-bromo-4,5-benzotropone (26).
Scheme 58: Synthesis of 6-chloro-2,3-benzotropone (335) using LiCl and proposed intermediate 336.
Scheme 59: Reaction of 7-bromo-2,3-benzotropone (316) with methylamine.
Scheme 60: Reactions of bromo-2,3-benzotropones 26 and 311 with dimethylamine.
Scheme 61: Reactions of bromobenzotropones 311 and 26 with NaOMe.
Scheme 62: Reactions of bromobenzotropones 26 and 312 with t-BuOK in the presence of DPIBF.
Scheme 63: Cobalt-catalyzed reductive cross-couplings of 7-bromo-2,3-benzotropone (316) with cyclic α-bromo en...
Figure 15: Cycloadduct 357 and its di-π-methane rearrangement product 358.
Scheme 64: Catalytic hydrogenation of 2-chloro-4,5-benzotropone (311).
Scheme 65: Synthesis of dibromo-benzotropones from benzotropones.
Scheme 66: Bromination/dehydrobromination of benzosuberone (162).
Scheme 67: Some transformations of isomeric dibromo-benzotropones 261A/B.
Scheme 68: Transformations of benzotropolone 239B to halobenzotropolones 369–371.
Figure 16: Bromobenzotropolones 372–376 and 290 prepared via bromination/dehydrobromination strategy.
Scheme 69: Synthesis of some halobenzotropolones 289, 377 and 378.
Figure 17: Bromo-chloro-derivatives 379–381 prepared via chlorination.
Scheme 70: Synthesis of 7-iodo-3,4-benzotropolone (382).
Scheme 71: Hydrogenation of bromobenzotropolones 369 and 370.
Scheme 72: Debromination reactions of mono- and dibromides 290 and 375.
Figure 18: Nitratation and oxidation products of some halobenzotropolenes.
Scheme 73: Azo-coupling reactions of some halobenzotropolones 294, 375 and 378.
Figure 19: Four possible isomers of dibenzotropones 396–399.
Figure 20: Resonance structures of tribenzotropone (400).
Scheme 74: Two synthetic pathways for tribenzotropone (400).
Scheme 75: Synthesis of tribenzotropone (400) from dibenzotropone 399.
Scheme 76: Synthesis of tribenzotropone (400) from 9,10-phenanthraquinone (406).
Scheme 77: Synthesis of tribenzotropone (400) from trifluoromethyl-substituted arene 411.
Figure 21: Dibenzosuberone (414).
Figure 22: Reduction products 415 and 416 of tribenzotropone (400).
Figure 23: Structures of tribenzotropone dimethyl ketal 417 and 4-phenylfluorenone (412) and proposed intermed...
Figure 24: Structures of benzylidene- and methylene-9H-tribenzo[a,c,e][7]annulenes 419 and 420 and chiral phos...
Figure 25: Structures of tetracyclic alcohol 422, p-quinone methide 423 and cation 424.
Figure 26: Structures of host molecules 425–427.
Scheme 78: Synthesis of non-helical overcrowded derivatives syn/anti-431.
Figure 27: Hexabenzooctalene 432.
Figure 28: Structures of possible eight isomers 433–440 of naphthotropone.
Scheme 79: Synthesis of naphthotropone 437 starting from 1-phenylcycloheptene (441).
Scheme 80: Synthesis of 10-hydroxy-11H-cyclohepta[a]naphthalen-11-one (448) from diester 445.
Scheme 81: Synthesis of naphthotropone 433.
Scheme 82: Synthesis of naphthotropones 433 and 434 via cycloaddition reaction.
Scheme 83: Synthesis of naphthotropone 434 starting from 452.
Figure 29: Structures of tricarbonyl(tropone)irons 458, and possible cycloadducts 459.
Scheme 84: Synthesis of naphthotropone 436.
Scheme 85: Synthesis of precursor 465 for naphthotropone 435.
Scheme 86: Generation of naphthotropone 435 from 465.
Figure 30: Structures of tropylium cations 469 and 470.
Figure 31: Structures of tropylium ions 471+.BF4−, 472+.BF4−, and 473+.BF4−.
Scheme 87: Synthesis of tropylium ions 471+.BF4− and 479+.ClO4−.
Scheme 88: Synthesis of 1- and 2-methylanthracene (481 and 482) via carbene–carbene rearrangement.
Figure 32: Trapping products 488–490.
Scheme 89: Generation and chemistry of a naphthoannelated cycloheptatrienylidene-cycloheptatetraene intermedia...
Scheme 90: Proposed intermediates and reaction pathways for adduct 498.
Scheme 91: Exited-state intramolecular proton transfer of 505.
Figure 33: Benzoditropones 506 and 507.
Scheme 92: Synthesis of benzoditropone 506e.
Scheme 93: Synthetic approaches for dibenzotropone 507 via tropone (1).
Scheme 94: Formation mechanisms of benzoditropone 507 and 516 via 515.
Scheme 95: Synthesis of benzoditropones 525 and 526 from pyromellitic dianhydride (527).
Figure 34: Possible three benzocyclobutatropones 534–536.
Scheme 96: Synthesis of benzocyclobutatropones 534 and 539.
Scheme 97: Synthesis attempts for benzocyclobutatropone 545.
Scheme 98: Generation and trapping of symmetric benzocyclobutatropone 536.
Scheme 99: Synthesis of chloro-benzocyclobutatropone 552 and proposed mechanism of fluorenone derivatives.
Scheme 100: Synthesis of tropolone analogue 559.
Scheme 101: Synthesis of tropolones 561 and 562.
Figure 35: o/p-Tropoquinone rings (563 and 564) and benzotropoquinones (565–567).
Scheme 102: Synthesis of benzotropoquinone 566.
Scheme 103: Synthesis of benzotropoquinone 567 via a Diels–Alder reaction.
Figure 36: Products 575–577 through 1,2,3-benzotropoquinone hydrate 569.
Scheme 104: Structures 578–582 prepared from tropoquinone 567.
Figure 37: Two possible structures 583 and 584 for dibenzotropoquinone, and precursor compound 585 for 583.
Scheme 105: Synthesis of saddle-shaped ketone 592 using dibenzotropoquinone 584.
CF3SO2X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF3SO2Na
- Hélène Guyon,
- Hélène Chachignon and
- Dominique Cahard
Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272
- 27, which was reduced into 28 prior to be converted into nitrogen heterocycles via [1,3]-hydride shift and cyclisation steps (Scheme 12). The reaction was regioselective and had a broad scope. This application of alkene trifluoromethylation provided a convenient entry to trifluoromethylated nitrogen
- heterocycles. Subsequently, a photoredox-catalysed azotrifluoromethylation of unactivated alkenes was developed by Chen, Xiao and co-workers [32]. The scope was broad for a variety of unactivated alkenes, functionalised or not, and aryldiazonium salts (Scheme 13). Interestingly, the method did not require
Graphical Abstract
Scheme 1: Trifluoromethylation of enol acetates by Langlois.
Scheme 2: Trifluoromethylation of (het)aryl enol acetates.
Scheme 3: Mechanism for the trifluoromethylation of enol acetates.
Scheme 4: Oxidative trifluoromethylation of unactivated olefins and mechanistic pathway.
Scheme 5: Oxidative trifluoromethylation of acetylenic substrates.
Scheme 6: Metal free trifluoromethylation of styrenes.
Scheme 7: Synthesis of α-trifluoromethylated ketones by oxytrifluoromethylation of heteroatom-functionalised ...
Scheme 8: Catalysed photoredox trifluoromethylation of vinyl azides.
Scheme 9: Oxidative difunctionalisation of alkenyl MIDA boronates.
Scheme 10: Synthesis of β-trifluoromethyl ketones from cyclopropanols.
Scheme 11: Aryltrifluoromethylation of allylic alcohols.
Scheme 12: Cascade multicomponent synthesis of nitrogen heterocycles via azotrifluoromethylation of alkenes.
Scheme 13: Photocatalytic azotrifluoromethylation of alkenes with aryldiazonium salts and CF3SO2Na.
Scheme 14: Copper-promoted intramolecular aminotrifluoromethylation of alkenes with CF3SO2Na.
Scheme 15: Oxytrifluoromethylation of alkenes with CF3SO2Na and hydroxamic acid.
Scheme 16: Manganese-catalysed oxytrifluoromethylation of styrene derivatives.
Scheme 17: Oxytrifluoromethylation of alkenes with NMP/O2 and CF3SO2Na.
Scheme 18: Intramolecular oxytrifluoromethylation of alkenes.
Scheme 19: Hydrotrifluoromethylation of styrenyl alkenes and unactivated aliphatic alkenes.
Scheme 20: Hydrotrifluoromethylation of electron-deficient alkenes.
Scheme 21: Hydrotrifluoromethylation of alkenes by iridium photoredox catalysis.
Scheme 22: Iodo- and bromotrifluoromethylation of alkenes by CF3SO2Na/I2O5 or CF3SO2Na / NaBrO3.
Scheme 23: N-methyl-9-mesityl acridinium and visible-light-induced chloro-, bromo- and SCF3 trifluoromethylati...
Scheme 24: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na / TBHP by Lipshutz.
Scheme 25: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/TBHP reported by Lei.
Scheme 26: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/(NH4)2S2O8.
Scheme 27: Metal-free carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/K2S2O8 reported by Wang.
Scheme 28: Metal-free carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/PIDA reported by Fu.
Scheme 29: Metal-free cascade trifluoromethylation/cyclisation of N-arylmethacrylamides (a) and enynes (b) wit...
Scheme 30: Trifluoromethylation/cyclisation of N-arylcinnamamides: Synthesis of 3,4-disubstituted dihydroquino...
Scheme 31: Trifluoromethylation/cyclisation of aromatic-containing unsaturated ketones.
Scheme 32: Chemo- and regioselective cascade trifluoromethylation/heteroaryl ipso-migration of unactivated alk...
Scheme 33: Copper-mediated 1,2-bis(trifluoromethylation) of alkenes.
Scheme 34: Trifluoromethylation of aromatics with CF3SO2Na reported by Langlois.
Scheme 35: Baran’s oxidative C–H trifluoromethylation of heterocycles.
Scheme 36: Trifluoromethylation of acetanilides and anilines.
Scheme 37: Trifluoromethylation of heterocycles in water.
Scheme 38: Trifluoromethylation of coumarins in a continuous-flow reactor.
Scheme 39: Oxidative trifluoromethylation of coumarins, quinolines and pyrimidinones.
Scheme 40: Oxidative trifluoromethylation of pyrimidinones and pyridinones.
Scheme 41: Phosphovanadomolybdic acid-catalysed direct C−H trifluoromethylation.
Scheme 42: Oxidative trifluoromethylation of imidazopyridines and imidazoheterocycles.
Scheme 43: Oxidative trifluoromethylation of imidazoheterocycles and imidazoles in ionic liquid/water.
Scheme 44: Oxidative trifluoromethylation of 8-aminoquinolines.
Scheme 45: Oxidative trifluoromethylation of various 8-aminoquinolines using the supported catalyst CS@Cu(OAc)2...
Scheme 46: Oxidative trifluoromethylation of the naphthylamide 70.
Scheme 47: Oxidative trifluoromethylation of various arenes in the presence of CF3SO2Na and sodium persulfate.
Scheme 48: Trifluoromethylation of electron-rich arenes and unsymmetrical biaryls with CF3SO2Na in the presenc...
Figure 1: Trifluoromethylated coumarin and flavone.
Scheme 49: Metal-free trifluoromethylation catalysed by a photoredox organocatalyst.
Scheme 50: Quinone-mediated trifluoromethylation of arenes and heteroarenes.
Scheme 51: Metal- and oxidant-free photochemical trifluoromethylation of arenes.
Scheme 52: Copper-mediated trifluoromethylation of arenediazonium tetrafluoroborates.
Scheme 53: Oxidative trifluoromethylation of aryl- and heteroarylboronic acids.
Scheme 54: Oxidative trifluoromethylation of aryl- and vinylboronic acids.
Scheme 55: Oxidative trifluoromethylation of unsaturated potassium organotrifluoroborates.
Scheme 56: Oxidative trifluoromethylation of (hetero)aryl- and vinyltrifluoroborates.
Scheme 57: Copper−catalysed decarboxylative trifluoromethylation of cinnamic acids.
Scheme 58: Iron-mediated decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids.
Scheme 59: Cu/Ag-catalysed decarboxylative trifluoromethylation of cinnamic acids.
Scheme 60: I2O5-Promoted decarboxylative trifluoromethylation of cinnamic acids.
Scheme 61: Silver(I)-catalysed denitrative trifluoromethylation of β-nitrostyrenes.
Scheme 62: Copper-catalysed direct trifluoromethylation of styrene derivatives.
Scheme 63: Transition-metal-free synthesis of β-trifluoromethylated enamines.
Scheme 64: I2O5-mediated iodotrifluoromethylation of alkynes.
Scheme 65: Silver-catalysed tandem trifluoromethylation/cyclisation of aryl isonitriles.
Scheme 66: Photoredox trifluoromethylation of 2-isocyanobiphenyls.
Scheme 67: Trifluoromethylation of potassium alkynyltrifluoroborates with CF3SO2Na.
Scheme 68: N-trifluoromethylation of nitrosoarenes with CF3SO2Na (SQ: semiquinone).
Scheme 69: Trifluoromethylation of disulfides with CF3SO2Na.
Scheme 70: Trifluoromethylation of thiols with CF3SO2Na/I2O5.
Scheme 71: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/(EtO)2P(O)H/CuCl/DMSO.
Scheme 72: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/(EtO)2P(O)H/TMSCl.
Scheme 73: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PPh3/N-chlorophthalimide.
Scheme 74: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PCl3.
Scheme 75: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PCl3.
Scheme 76: Trifluoromethylsulfenylation of aryl iodides with in situ generated CuSCF3 (DMI: 1,3-dimethyl-2-imi...
Scheme 77: Pioneering trifluoromethylsulfinylation of N, O, and C-nucleophiles.
Scheme 78: Trifluoromethylsulfinylation of (1R,2S)-ephedrine (Im: imidazole; DIEA: N,N-diisopropylethylamine).
Scheme 79: Trifluoromethylsulfinylation of substituted benzenes with CF3SO2Na/CF3SO3H.
Scheme 80: Trifluoromethylsulfinylation of indoles with CF3SO2Na/P(O)Cl3.
Scheme 81: Trifluoromethylsulfinylation of indoles with CF3SO2Na/PCl3.
Scheme 82: Formation of triflones from benzyl bromides (DMA: dimethylacetamide).
Scheme 83: Formation of α-trifluoromethylsulfonyl ketones, esters, and amides.
Scheme 84: Allylic trifluoromethanesulfonylation of aromatic allylic alcohols.
Scheme 85: Copper-catalysed couplings of aryl iodonium salts with CF3SO2Na.
Scheme 86: Palladium-catalysed trifluoromethanesulfonylation of aryl triflates and chlorides with CF3SO2Na.
Scheme 87: Copper-catalysed coupling of arenediazonium tetrafluoroborates with CF3SO2Na.
Scheme 88: Synthesis of phenyltriflone via coupling of benzyne with CF3SO2Na.
Scheme 89: Synthesis of 1-trifluoromethanesulfonylcyclopentenes from 1-alkynyl-λ3-bromanes and CF3SO2Na.
Scheme 90: One-pot synthesis of functionalised vinyl triflones.
Scheme 91: Regioselective synthesis of vinyltriflones from styrenes.
Scheme 92: Trifluoromethanesulfonylation of alkynyl(phenyl) iodonium tosylates by CF3SO2Na.
Scheme 93: Synthesis of thio- and selenotrifluoromethanesulfonates.
Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective
- Yaroslav D. Boyko,
- Valentin S. Dorokhov,
- Alexey Yu. Sukhorukov and
- Sema L. Ioffe
Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220
- phosphinyl nitrosoalkenes NSA15 (derived from the corresponding α-bromooximes) with electron-rich nitrogen heterocycles to give adducts 69 is described and the comparison of electrophilic aromatic substitution (1) and cycloaddition (2) routes is discussed [59] (Scheme 24). Quantum-chemical calculations
Graphical Abstract
Scheme 1: Precursors of nitrosoalkenes NSA.
Scheme 2: Reactions of cyclic α-chlorooximes 1 with 1,3-dicarbonyl compounds.
Scheme 3: C-C-coupling of N,N-bis(silyloxy)enamines 3 with 1,3-dicarbonyl compounds.
Scheme 4: Reaction of N,N-bis(silyloxy)enamines 3 with nitronate anions.
Scheme 5: Reaction of α-chlorooximes TBS ethers 2 with ester enolates.
Scheme 6: Assembly of bicyclooctanone 14 via an intramolecular cyclization of nitrosoalkene NSA2.
Scheme 7: A general strategy for the assembly of bicyclo[2.2.1]heptanes via an intramolecular cyclization of ...
Scheme 8: Stereochemistry of Michael addition to cyclic nitrosoalkene NSA3.
Scheme 9: Stereochemistry of Michael addition to acyclic nitrosoalkenes NSA4.
Scheme 10: Stereochemistry of Michael addition to γ-alkoxy nitrosoalkene NSA5.
Scheme 11: Oppolzer’s total synthesis of 3-methoxy-9β-estra(1,3,5(10))trien(11,17)dione (25).
Scheme 12: Oppolzer’s total synthesis of (+/−)-isocomene.
Figure 1: Alkaloids synthesized using stereoselective Michael addition to conjugated nitrosoalkenes.
Scheme 13: Weinreb’s total synthesis of alstilobanines A, E and angustilodine.
Scheme 14: Weinreb’s approach to the core structure of apparicine alkaloids.
Scheme 15: Weinreb’s synthesis of (+/−)-myrioneurinol via stereoselective conjugate addition of malonate to ni...
Scheme 16: Reactions of cyclic α-chloro oximes with Grignard reagents.
Scheme 17: Corey’s synthesis of (+/−)-perhydrohistrionicotoxin.
Scheme 18: Addition of Gilman’s reagents to α,β-epoxy oximes 53.
Scheme 19: Addition of Gilman’s reagents to α-chlorooximes.
Scheme 20: Reaction of silyl nitronate 58 with organolithium reagents via nitrosoalkene NSA12.
Scheme 21: Reaction of β-ketoxime sulfones 61 and 63 with lithium acetylides.
Scheme 22: Electrophilic addition of nitrosoalkenes NSA14 to electron-rich arenes.
Scheme 23: Addition of nitrosoalkenes NSA14 to pyrroles and indoles.
Scheme 24: Reaction of phosphinyl nitrosoalkenes NSA15 with indole.
Scheme 25: Reaction of pyrrole with α,α’-dihalooximes 70.
Scheme 26: Synthesis of indole-derived psammaplin A analogue 72.
Scheme 27: Synthesis of tryptophanes by reduction of oximinoalkylated indoles 68.
Scheme 28: Ottenheijm’s synthesis of neoechinulin B analogue 77.
Scheme 29: Synthesis of 1,2-dihydropyrrolizinones 82 via addition of pyrrole to ethyl bromopyruvate oxime.
Scheme 30: Kozikowski’s strategy to indolactam-based alkaloids via addition of indoles to ethyl bromopyruvate ...
Scheme 31: Addition of cyanide anion to nitrosoalkenes and subsequent cyclization to 5-aminoisoxazoles 86.
Scheme 32: Et3N-catalysed addition of trimethylsilyl cyanide to N,N-bis(silyloxy)enamines 3 leading to 5-amino...
Scheme 33: Addition of TMSCN to allenyl N-siloxysulfonamide 89.
Scheme 34: Reaction of nitrosoallenes NSA16 with malodinitrile and ethyl cyanoacetic ester.
Scheme 35: [4 + 1]-Annulation of nitrosoalkenes NSA with sulfonium ylides 92.
Scheme 36: Reaction of diazo compounds 96 with nitrosoalkenes NSA.
Scheme 37: Tandem Michael addition/oxidative cyclization strategy to isoxazolines 100.
Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds
- Alexey Yu. Dubovtsev,
- Maksim V. Dmitriev,
- Аndrey N. Maslivets and
- Michael Rubin
Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218
- between two alternative directions affording derivatives of partially hydrogenated indole or benzofurane. The control of this regioselectivity is efficiently governed by steric effects at the hydrazone moiety of the ketazinone reagent. Keywords: nitrogen heterocycles; oxygen heterocycles; pyrrolediones
Graphical Abstract
Scheme 1: Spirocyclization of enamines with 5-methoxycarbonyl-1H-pyrrolediones.
Scheme 2: Non-catalyzed spirocyclization of enoles (vinylogous carbonates and carbamates) with 5-methoxycarbo...
Scheme 3: Acid-catalyzed spirocyclization of enoles (vinylogous carboxylates) with 5-alkoxycarbonyl-1H-pyrrol...
Figure 1: ORTEP drawing of compound 12ab (CCDC 1546062) showing 50% probability amplitude displacement ellips...
Scheme 4: Formation of mono-imines and mono-hydrazones of 1,3-cyclohexanediones and tautomeric equilibrium be...
Scheme 5: Spirocyclizations involving non-bulky ketazinones 17 and 5-alkoxycarbonyl-1H-pyrrolediones 9.
Figure 2: ORTEP drawing of compound 21ab (CCDC 1546063) showing 50% probability amplitude displacement ellips...
Figure 3: ORTEP drawing of compound 22a (CCDC 1546065) showing 50% probability amplitude displacement ellipso...
Scheme 6: Spirocyclizations involving bulky ketazinones 22 and 5-alkoxycarbonyl-1H-pyrrolediones 9.
Figure 4: ORTEP drawing of compound 23aa (CCDC 1546064) showing 50% probability amplitude displacement ellips...
Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains
- Layal Hariss,
- Kamal Bou Hadir,
- Mirvat El-Masri,
- Thierry Roisnel,
- René Grée and
- Ali Hachem
Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208
- propargylic derivatives 4 [28] with aromatic aldehydes. Then, the DBU-mediated isomerization afforded the desired enones 6a–e in 21–66% yields (Scheme 2 and Table 1). For the synthesis of the desired nitrogen heterocycles, we started our study by reacting 6a with 2-aminopyridine in the presence of AlCl3 and
Graphical Abstract
Figure 1: Representative examples of bioactive imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, imidazopyr...
Scheme 1: Retrosynthetic scheme for the preparation of our target molecules A.
Scheme 2: Synthesis of enones 6 with a gem-difluoroalkyl side chain.
Scheme 3: Synthesis of 7a.
Figure 2: Structures of 7a and 7e by X-ray crystallography analysis.
Scheme 4: One-pot synthesis of 7a.
High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units
- Marco Leonardi,
- Mercedes Villacampa and
- J. Carlos Menéndez
Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190
- relevance of nitrogen heterocycles in the generation of bioactive molecules, medicinal chemists would greatly benefit from the ability to build two heterocyclic systems at both ends of the spacer chain in a single maneuver. Further advantages in terms of synthetic efficiency would be gained if the key
Graphical Abstract
Scheme 1: Our synthetic planning and structural diversity of starting materials employed in our work.
Scheme 2: Pseudo five-component reactions affording symmetrical bispyrrole derivatives joined by a spacer.
Figure 1: Scope of the synthesis of symmetrical bispyrrole derivatives.
Scheme 3: A pseudo-seven-component reaction that affords a terpyrrole derivative with a functionalized spacer....
Scheme 4: Homodimerization of 2-allyl- and 2-homoallylpyrroles via cross-metathesis reactions.
Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds
- Santanu Hati,
- Ulrike Holzgrabe and
- Subhabrata Sen
Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162
- /bjoc.13.162 Abstract Nitrogen heteroarenes form an important class of compounds which can be found in natural products, synthetic drugs, building blocks etc. Among the diverse strategies that were developed for the synthesis of nitrogen heterocycles, oxidative dehydrogenation is extremely effective
- nitrogen heteroarenes. Keywords: aerobic oxidation; bioinspired Flavin mimics; nitrogen heteroarenes; organo catalytic; oxidative dehydrogenation; Introduction By virtue of their presence in bioactive natural products and active pharmaceutical ingredients, nitrogen heterocycles and heteroaromatics form
- reactions are one of the key synthetic strategies that are applied to generate various nitrogen heterocycles and subsequent aromatization of these heterocycles afforded the corresponding heteroaromatic derivatives [19]. The aromatization of nitrogen heterocycles is facilitated mainly by dehydrogenation of
Graphical Abstract
Figure 1: Representative bioactive heterocycles.
Scheme 1: The concept of oxidative dehydrogenation.
Scheme 2: IBX-mediated oxidative dehydrogenation of various heterocycles [31-34].
Scheme 3: Potential mechanism of IBX-mediated oxidative dehydrogenation of N-heterocycles [31-34].
Scheme 4: IBX-mediated room temperature one-pot condensation–oxidative dehydrogenation of o-aminobenzylamines....
Scheme 5: Anhydrous cerium chloride-catalyzed, IBX-mediated oxidative dehydrogenation of various heterocycles...
Scheme 6: Oxidative dehydrogenation of quinazolinones with I2 and DDQ [37-40].
Scheme 7: DDQ-mediated oxidative dehydrogenation of thiazolidines and oxazolidines.
Scheme 8: Oxone-mediated oxidative dehydrogenation of intermediates from o-phenylenediamine and o-aminobenzyl...
Scheme 9: Transition metal-free oxidative cross-dehydrogenative coupling.
Scheme 10: NaOCl-mediated oxidative dehydrogenation.
Scheme 11: NBS-mediated oxidative dehydrogenation of tetrahydro-β-carbolines.
Scheme 12: One-pot synthesis of various methyl(hetero)arenes from o-aminobenzamide in presence of di-tert-buty...
Scheme 13: Oxidative dehydrogenation of 1, 4-DHPs.
Scheme 14: Synthesis of quinazolines in the presence of MnO2.
Scheme 15: Selenium dioxide and potassium dichromate-mediated oxidative dehydrogenation of tetrahydro-β-carbol...
Scheme 16: Synthesis of substituted benzazoles in the presence of barium permanganate.
Scheme 17: Oxidative dehydrogenation with phenanthroline-based catalysts. PPTS = pyridinium p-toluenesulfonic ...
Scheme 18: Oxidative dehydrogenation with Flavin mimics.
Scheme 19: o-Quinone based bioinspired catalysts for the synthesis of dihydroisoquinolines.
Scheme 20: Cobalt-catalyzed aerobic dehydrogenation of Hantzch 1,4-DHPs and pyrazolines.
Scheme 21: Mechanism of cobalt-catalyzed aerobic dehydrogenation of Hantzch 1,4-DHPs.
Scheme 22: DABCO and TEMPO-catalyzed aerobic oxidative dehydrogenation of quinazolines and 4H-3,1-benzoxazines....
Scheme 23: Putative mechanism for Cu(I)–DABCO–TEMPO catalyzed aerobic oxidative dehydrogenation of tetrahydroq...
Scheme 24: Potassium triphosphate modified Pd/C catalysts for the oxidative dehydrogenation of tetrahydroisoqu...
Scheme 25: Ruthenium-catalyzed polycyclic heteroarenes.
Scheme 26: Plausible mechanism of the ruthenium-catalyzed dehydrogenation.
Scheme 27: Bi-metallic platinum/iridium alloyed nanoclusters and 5,5’,6,6’-tetrahydroxy-3,3,3’,3’-tetramethyl-...
Scheme 28: Magnesium iodide-catalyzed synthesis of quinazolines.
Scheme 29: Ferrous chloride-catalyzed aerobic dehydrogenation of 1,2,3,4-tetrahydroquinolines.
Scheme 30: Cu(I)-catalyzed oxidative aromatization of indoles.
Scheme 31: Putative mechanism of the transformation.
Scheme 32: Oxidative dehydrogenation of pyrimidinones and pyrimidines.
Scheme 33: Putative mechanisms (radical and metal-catalyzed) of the transformation.
Scheme 34: Ferric chloride-catalyzed, TBHP-oxidized synthesis of substituted quinazolinones and arylquinazolin...
Scheme 35: Iridium-catalyzed oxidative dehydrogenation of quinolines.
Scheme 36: Microwave-assisted synthesis of β-carboline with a catalytic amount of Pd/C in lithium carbonate at...
Scheme 37: 4-Methoxy-TEMPO-catalyzed aerobic oxidative synthesis of 2-substituted benzazoles.
Scheme 38: Plausible mechanism of the 4-methoxy-TEMPO-catalyzed transformation.
Scheme 39: One-pot synthesis of 2-arylquinazolines, catalyzed by 4-hydroxy-TEMPO.
Scheme 40: Oxidative dehydrogenation – a key step in the synthesis of AZD8926.
Scheme 41: Catalytic oxidative dehydrogenation of tetrahydroquinolines to afford bioactive molecules.
Scheme 42: Iodobenzene diacetate-mediated synthesis of β-carboline natural products.
Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine
- Jimena E. Díaz,
- Silvia Ranieri,
- Nadia Gruber and
- Liliana R. Orelli
Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145
- -assisted ring closure of the corresponding aminoamides promoted by ethyl polyphosphate (PPE). Keywords: dihydroquinazolines; microwaves; N-acylations; N-alkylations; PPE; Introduction Nitrogen heterocycles are part of many drugs and represent structures with wide therapeutic potential. Therefore, much
Graphical Abstract
Figure 1: 3,4-Dihydroquinazolines 1 and 1,4-dihydroquinazolines 2.
Scheme 1: Synthetic pathways for the preparation of 3,4-dihydroquinazolines 1 and 1,4-dihydroquinazolines 2.
Scheme 2: Synthesis of compounds 3a–c.
Scheme 3: Benzylic oxidation of 1,4-dihydroquinazolines (a) and 3,4-dihydroquinazolines (b).
N-Propargylamines: versatile building blocks in the construction of thiazole cores
- S. Arshadi,
- E. Vessally,
- L. Edjlali,
- R. Hosseinzadeh-Khanmiri and
- E. Ghorbani-Kalhor
Beilstein J. Org. Chem. 2017, 13, 625–638, doi:10.3762/bjoc.13.61
- synthesis of various nitrogen heterocycles and complex natural products. In this regard, recently an impressive increase in the number of publications on the preparation of thiazoles and their hydrogenated analogues through inter- and intramolecular cyclization of N-propargylamine derivatives appeared in
Graphical Abstract
Figure 1: Selected examples of bioactive thiazole derivatives.
Figure 2: Some natural sources of thiazoles.
Figure 3: Some important thiazole-based compounds derived from N-propargylamines.
Scheme 1: The synthesis of thiazole-2-thiones 3 through the thermal cyclocondensation of N-propargylamines 1 ...
Scheme 2: (a) One-pot synthesis of 2-benzylthiazolo[3,2-a]benzimidazoles 6 through a base-catalyzed cascade r...
Scheme 3: (a) Synthesis of 2-iminothiazolidines 11 from N-propargylamines 9 and isothiocyanates 10. (b) Synth...
Scheme 4: (a) Synthesis of 2-aminothiazoles 17 through the reaction of ethyl 4-aminobut-2-ynoate salts 15 wit...
Scheme 5: Synthesis of 5-(iodomethylene)-3-methylthiazolidines 27 described by Zhou.
Scheme 6: Mechanism that accounts for the formation of 27.
Scheme 7: Clausen’s synthesis of fluorescein thiazolidines 30.
Scheme 8: Synthesis of multiply substituted thiazolidines 33 from N-propargylamines 32 and blocked N-isothioc...
Scheme 9: (a) Microwave-assisted cyclization of N-propargyl thiocarbamate 34. (b) Synthesis of thiazoles 39 t...
Scheme 10: Synthesis of thiazolidines 42 (42’) from the reaction of β-oxodithioesters 40 (40’) with N-propargy...
Scheme 11: Synthesis of 5-(dibromomethyl)thiazoles 44 via halocyclization of N-propargylamines 43 described by...
Scheme 12: Synthesis of dihydrothiazoles 46 through the treatment of N-propargylamides 45 with Lawesson’s reag...
Scheme 13: Synthesis of thiazoles 49 by treatment of silyl-protected N-propargylamines 47 with benzotriazolylt...
Scheme 14: Mechanism proposed to explain the synthesis of 2,5-disubstituted thiazoles 49 developed by Sasmal.
Scheme 15: Mo-catalyzed cyclization of N-propargylthiocarbamate 50.
Scheme 16: (a) DABCO-mediated intramolecular cyclization of N-(propargylcarbamothioyl)amides 53 to the corresp...
Scheme 17: Proposed mechanism for the generation of the iodine-substituted 4H-1,3-thiazines 56 and 4,5-dihydro...
Scheme 18: Au(III)-catalyzed synthesis of 5-alkylidenedihydrothiazoles 58 developed by Stevens.
An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy
- Alexei N. Izmest’ev,
- Galina A. Gazieva,
- Natalya V. Sigay,
- Sergei A. Serkov,
- Valentina A. Karnoukhova,
- Vadim V. Kachala,
- Alexander S. Shashkov,
- Igor E. Zanin,
- Angelina N. Kravchenko and
- Nina N. Makhova
Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216
- ; nitrogen heterocycles; spiro compounds; Introduction A global trend in modern organic chemistry is the design of molecular systems with various degrees of complexity to maximize the incorporation of useful properties while optimizing cost and efficiency [1]. A very extended and powerful approach for
Graphical Abstract
Figure 1: Bioactive 2,3’-spiropyrrolidinyloxindoles.
Scheme 1: Earlier studied cycloaddition reaction.
Scheme 2: Synthesis of dipolarophiles 1a–c.
Scheme 3: Synthesis of dispirocompounds 4a–o.
Figure 2: Synthesis of dispiro compounds 4a–o. Reaction conditions: heating the mixture of compounds 1 (0.5 m...
Scheme 4: Synthesis of dipolarophiles 1d–f.
Figure 3: Synthesis of dispiro compounds 4p–t. Reaction conditions: heating the solution of compounds 1 (0.5 ...
Figure 4: Key interactions in {1H-13C}HMBC spectrum of 4f.
Figure 5: General view of 4c in the crystal in thermal ellipsoids representation (50% probability). Hydrogen ...
Figure 6: General view of 4e in the crystal in thermal ellipsoids representation (40% probability). Hydrogen ...
Figure 7: General view of 4r in the crystal in thermal ellipsoids representation (50% probability). Hydrogen ...
Figure 8: Modes of approach of azomethine ylide (R = H, Ph).
Microwave-assisted cyclizations promoted by polyphosphoric acid esters: a general method for 1-aryl-2-iminoazacycloalkanes
- Jimena E. Díaz,
- María C. Mollo and
- Liliana R. Orelli
Beilstein J. Org. Chem. 2016, 12, 2026–2031, doi:10.3762/bjoc.12.190
- synthesis. Keywords: cyclic amidines; medium size heterocycles; microwaves; PPE; PPSE; Introduction The synthesis of new nitrogen heterocycles has a great interest in medicinal chemistry since they are part of many drugs and represent structures with a wide therapeutic potential [1][2]. 2
Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides
- Lena Huck,
- Juan F. González,
- Elena de la Cuesta and
- J. Carlos Menéndez
Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166
- . Their transformation into β-trifluoroacetamido-α-ketoamide and α,β-diketoamide frameworks was also achieved in a single step. Keywords: α-ketoamides; aziridines; multicomponent reactions; nitrogen heterocycles; one-pot reactions; peptide mimics; vicinal tricarbonyl compounds; Introduction Aziridine
- scaffolds, we examined their one-pot transformation into α,β-diketoamides and the transformation of the latter compounds into nitrogen heterocycles bearing a peptide side chain (Scheme 1). Results and Discussion The starting 3-arylmethylene-2,5-piperazinediones 1 were readily available by aldol condensation
- explored briefly their direct preparation from compounds 2, together with their application to the synthesis of nitrogen heterocycles bearing a peptide side chain. We discovered that treatment of representative aziridines 2 with perchloric acid in a THF–water reaction medium led to the isolation of the
Graphical Abstract
Scheme 1: Summary of the work described in this paper.
Scheme 2: Synthesis of aziridines 2.
Figure 1: NOE effects in compound 2f.
Scheme 3: Mechanistic proposal accounting for the chemo- and diastereoselective formation of aziridines 2.
Scheme 4: Transformation of aziridines 2 into β-trifluoroacetamido-α-ketoamides 6.
Scheme 5: Two mechanistic proposals explaining the formation of compounds 6.
Scheme 6: Transformation of aziridines 2 into vicinal tricarbonyl compounds 11 and transformation of the latt...
Scheme 7: Mechanistic proposal for the transformation of aziridines 2 into compounds 11.
Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides
- Franziska Hemmerling and
- Frank Hahn
Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148
- [4]. Oxygen heterocycles are mainly found in carbohydrates, polyketides, peptides and terpenoids. Nitrogen heterocycles are part of peptides and alkaloids. Both can of course also occur in the respective hybrid natural products. Sulphur-containing heterocycles are present in few polyketides and more
Graphical Abstract
Scheme 1: Schematic description of the cyclisation reaction catalysed by TE domains. In most cases, the nucle...
Scheme 2: Mechanisms for the formation of oxygen heterocycles. The degree of substitution can differ from tha...
Scheme 3: Pyran-ring formation in pederin (24) biosynthesis. Incubation of recombinant PedPS7 with substrate ...
Scheme 4: The domain AmbDH3 from ambruticin biosynthesis catalyses the dehydration of 25 and subsequent cycli...
Scheme 5: SalBIII catalyses dehydration of 29 and subsequent cyclisation to tetrahydropyran 30 [18].
Figure 1: All pyranonaphtoquinones contain either the naphtha[2,3-c]pyran-5,10-dione (32) or the regioisomeri...
Scheme 6: Pyran-ring formation in actinorhodin (34) biosynthesis. DNPA: 4-dihydro-9-hydroxy-1-methyl-10-oxo-3H...
Scheme 7: Pyran formation in granaticin (36) biosynthesis. DNPA: 4-dihydro-9-hydroxy-1-methyl-10-oxo-3H-napht...
Scheme 8: Pyran formation in alnumycin (37) biosynthesis. Adapted from [21].
Scheme 9: Biosynthesis of pseudomonic acid A (61). The pyran ring is initially formed in 57 after dehydrogena...
Scheme 10: Epoxidation–cyclisation leads to the formation of the tetrahydropyran ring in the western part of t...
Scheme 11: a) Nonactin (70) is formed from heterodimers of (−)(+)-dimeric nonactic acid and (+)(−)-dimeric non...
Figure 2: Pamamycins (73) are macrodiolide antibiotics containing three tetrahydrofuran moieties, which are a...
Scheme 12: A PS domain homolog in oocydin A (76) biosynthesis is proposed to catalyse furan formation via an o...
Scheme 13: Mechanism of oxidation–furan cyclisation by AurH, which converts (+)-deoxyaureothin (77) into (+)-a...
Scheme 14: Leupyrrin A2 (80) and the proposed biosynthesis of its furylidene moiety [69,70].
Scheme 15: Asperfuranone (93) biosynthesis, adapted from [75].
Figure 3: The four major aflatoxins produced by Aspergilli are the types B1, B2, G1 and G2 (94–97). In the di...
Scheme 16: Overview on aflatoxin B1 (94) biosynthesis. HOMST = 11-hydroxy-O-methylsterigmatocystin [78,79,82-106].
Scheme 17: A zipper mechanism leads to the formation of oxygen heterocycles in monensin biosynthesis [109-111].
Scheme 18: Formation of the 2,6-dioxabicyclo[3.2.1]octane (DBO) ring system in aurovertin B (118) biosynthesis ...
Figure 4: Structures of the epoxide-containing polyketides epothilone A (119) and oleandomycin (120) [123-125].
Scheme 19: Structures of phoslactomycin B (121) (a) and jerangolid A (122) (b). The heterocycle-forming steps ...
Scheme 20: a) Structures of rhizoxin (130) and cycloheximide (131). Model for the formation of δ-lactones (b) ...
Scheme 21: EncM catalyses a dual oxidation sequence and following processing of the highly reactive intermedia...
Figure 5: Mesomeric structures of tetronates [138,139].
Figure 6: Structures of tetronates for which gene clusters have been sequenced. The tetronate moiety is shown...
Scheme 22: Conserved steps for formation and processing in several 3-acyl-tetronate biosynthetic pathways were...
Scheme 23: In versipelostatin A (153) biosynthesis, VstJ is a candidate enzyme for catalysing the [4 + 2] cycl...
Scheme 24: a) Structures of some thiotetronate antibiotics. b) Biosynthesis of thiolactomycin (165) as propose...
Scheme 25: Aureusidine synthase (AS) catalyses phenolic oxidation and conjugate addition of chalcones leading ...
Scheme 26: a) Oxidative cyclisation is a key step in the biosynthesis of spirobenzofuranes 189, 192 and 193. b...
Scheme 27: A bicyclisation mechanism forms a β-lactone and a pyrrolidinone and removes the precursor from the ...
Scheme 28: Spontaneous cyclisation leads to off-loading of ebelactone A (201) from the PKS machinery [163].
Scheme 29: Mechanisms for the formation of nitrogen heterocycles.
Scheme 30: Biosynthesis of highly substituted α-pyridinones. a) Feeding experiments confirmed the polyketide o...
Scheme 31: Acridone synthase (ACS) catalyses the formation of 1,3-dihydroxy-N-methylacridone (224) by condensa...
Scheme 32: A Dieckmann condensation leads to the formation of a 3-acyl-4-hydroxypyridin-2-one 227 and removes ...
Scheme 33: a) Biosynthesis of the pyridinone tenellin (234). b) A radical mechanism was proposed for the ring-...
Scheme 34: a) Oxazole-containing PKS–NRPS-derived natural products oxazolomycin (244) and conglobatin (245). b...
Scheme 35: Structure of tetramic acids 251 (a) and major tautomers of 3-acyltetramic acids 252a–d (b). Adapted...
Scheme 36: Equisetin biosynthesis. R*: terminal reductive domain. Adapted from [202].
Scheme 37: a) Polyketides for which a similar biosynthetic logic was suggested. b) Pseurotin A (256) biosynthe...
Figure 7: Representative examples of PTMs with varying ring sizes and oxidation patterns [205,206].
Scheme 38: Ikarugamycin biosynthesis. Adapted from [209-211].
Scheme 39: Tetramate formation in pyrroindomycin aglycone (279) biosynthesis [213-215].
Scheme 40: Dieckmann cyclases catalyse tetramate or 2-pyridone formation in the biosynthesis of, for example, ...
Conjugate addition–enantioselective protonation reactions
- James P. Phelan and
- Jonathan A. Ellman
Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116
- reaction, Lou and Cheng explored the addition of various nitrogen [54], sulfur [55], and carbon nucleophiles [56][57] to α-branched vinyl ketones (Scheme 29). The nitrogen heterocycles benzotriazole (126a), triazole (126b), and 5-phenyltriazole (126c), all reacted smoothly with vinyl ketone 118. To achieve
Graphical Abstract
Figure 1: Two general pathways for conjugate addition followed by enantioselective protonation.
Scheme 1: Tomioka’s enantioselective addition of arylthiols to α-substituted acrylates.
Scheme 2: Sibi’s enantioselective hydrogen atom transfer reactions.
Scheme 3: Mikami’s addition of perfluorobutyl radical to α-aminoacrylate 11.
Scheme 4: Reisman’s Friedel–Crafts conjugate addition–enantioselective protonation approach toward tryptophan...
Scheme 5: Pracejus’s enantioselective addition of benzylmercaptan to α-aminoacrylate 20.
Scheme 6: Kumar and Dike’s enantioselective addition of thiophenol to α-arylacrylates.
Scheme 7: Tan’s enantioselective addition of aromatic thiols to 2-phthalimidoacrylates.
Scheme 8: Glorius’ enantioselective Stetter reactions with α-substituted acrylates.
Scheme 9: Dixon’s enantioselective addition of thiols to α-substituted acrylates.
Figure 2: Chiral phosphorous ligands.
Scheme 10: Enantioselective addition of arylboronic acids to methyl α-acetamidoacrylate.
Scheme 11: Frost’s enantioselective additions to dimethyl itaconate.
Scheme 12: Darses and Genet’s addition of potassium organotrifluoroborates to α-aminoacrylates.
Scheme 13: Proposed mechanism for enantioselective additions to α-aminoacrylates.
Scheme 14: Sibi’s addition of arylboronic acids to α-methylaminoacrylates.
Scheme 15: Frost’s enantioselective synthesis of α,α-dibenzylacetates 64.
Scheme 16: Rovis’s hydroheteroarylation of α-substituted acrylates with benzoxazoles.
Scheme 17: Proposed mechanism for the hydroheteroarylation of α-substituted acrylates with benzoxazoles.
Scheme 18: Sodeoka’s enantioselective addition of amines to N-benzyloxycarbonyl acrylamides 75 and 77.
Scheme 19: Proposed catalytic cycle for Sodeoka’s enantioselective addition of amines.
Scheme 20: Sibi’s enantioselective Friedel–Crafts addition of pyrroles to imides 84.
Scheme 21: Kobayashi’s enantioselective addition of malonates to α-substituted N-acryloyloxazolidinones.
Scheme 22: Chen and Wu’s enantioselective addition of thiophenol to N-methacryloyl benzamide.
Scheme 23: Tan’s enantioselective addition of secondary phosphine oxides and thiols to N-arylitaconimides.
Scheme 24: Enantioselective addition of thiols to α-substituted N-acryloylamides.
Scheme 25: Kobayashi’s enantioselective addition of thiols to α,β-unsaturated ketones.
Scheme 26: Feng’s enantioselective addition of pyrazoles to α-substituted vinyl ketones.
Scheme 27: Luo and Cheng’s addition of indoles to vinyl ketones by enamine catalysis.
Scheme 28: Curtin–Hammett controlled enantioselective addition of indole.
Scheme 29: Luo and Cheng’s enantioselective additions to α-branched vinyl ketones.
Scheme 30: Lou’s reduction–conjugate addition–enantioselective protonation.
Scheme 31: Luo and Cheng’s primary amine-catalyzed addition of indoles to α-substituted acroleins.
Scheme 32: Luo and Cheng’s proposed mechanism and transition state.
Figure 3: Shibasaki’s chiral lanthanum and samarium tris(BINOL) catalysts.
Scheme 33: Shibasaki’s enantioselective addition of 4-tert-butyl(thiophenol) to α,β-unsaturated thioesters.
Scheme 34: Shibasaki’s application of chiral (S)-SmNa3tris(binaphthoxide) catalyst 144 to the total synthesis ...
Scheme 35: Shibasaki’s cyanation–enantioselective protonation of N-acylpyrroles.
Scheme 36: Tanaka’s hydroacylation of acrylamides with aliphatic aldehydes.
Scheme 37: Ellman’s enantioselective addition of α-substituted Meldrum’s acids to terminally unsubstituted nit...
Scheme 38: Ellman’s enantioselective addition of thioacids to α,β,β-trisubstituted nitroalkenes.
Scheme 39: Hayashi’s enantioselective hydroarylation of diphenylphosphinylallenes.
Scheme 40: Hayashi’s enantioselective hydroarylation of diphenylphosphinylallenes.
Figure 4: Togni’s chiral ferrocenyl tridentate nickel(II) and palladium(II) complexes.
Scheme 41: Togni’s enantioselective hydrophosphination of methacrylonitrile.
Scheme 42: Togni’s enantioselective hydroamination of methacrylonitrile.
NeoPHOX – a structurally tunable ligand system for asymmetric catalysis
- Jaroslav Padevět,
- Marcus G. Schrems,
- Robin Scheil and
- Andreas Pfaltz
Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114
- . Consequently, a variety of other ligand classes derived from oxazolines or other nitrogen heterocycles were explored and eventually, several highly effective ligand systems were found that have considerably enhanced the range of functionalized and unfunctionalized olefins that can be hydrogenated with high
Graphical Abstract
Figure 1: Structural motifs of phospinooxazoline ligands.
Scheme 1: Retrosynthetic analysis for NeoPHOX ligands.
Scheme 2: Synthesis of 1st generation NeoPHOX Ir-complexes [19].
Figure 2: Asymmetric hydrogenation with iridium-NeoPHOX catalysts [19].
Figure 3: Employing L-valine as a starting material for C5 substituted oxazoline.
Scheme 3: Synthesis of a C(5)-disubstituted NeoPHOX-Ir complex.
Figure 4: Retrosynthetic analysis for NeoPHOX ligands derived from serine and threonine.
Scheme 4: Revisited synthetic strategy for the preparation of a threonine-based NeoPHOX ligand.
Scheme 5: Undesired β-lactam formation.
Scheme 6: Synthetic strategy for the synthesis of the serine-derived NeoPHOX ligand.
Scheme 7: Derivatization of the 2nd generation NeoPHOX ligands and formation of their iridium complexes.
Figure 5: Crystal structures of selected Ir-complexes. Hydrogen atoms, COD and BArF anions were omitted for c...
Scheme 8: Asymmetric palladium-catalyzed allylic substitution with rac-(E)-1,3-diphenylallyl acetate.
Scheme 9: Asymmetric palladium-catalyzed allylic substitution with rac-(E)-1,3-dimethylallyl acetate.
Scheme 10: Asymmetric palladium-catalyzed allylic substitution with a cyclic substrate.
