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Search for "scaffolds" in Full Text gives 558 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues
- Rashmi Singh,
- Tomas Horsten,
- Rashmi Prakash,
- Swapan Dey and
- Wim Dehaen
Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79
- presence of a catalytic amount of piperidine afforded pyridopsoralen 22 in 46% yield. Analogously, pyridopsoralen 23 was prepared from 16 by Knoevenagel condensation with diethyl malonate and subsequent lactonization with 62% yield (Scheme 4) [13]. To the best of our understanding, the scaffolds 21–23 are
- regioselective in forming 16, which is a valuable building block for various condensation reactions to yield a diverse set of products, such as polycyclic fused nitrochromenes 21 as well as pyridopsoralens 22 and 23. All these novel scaffolds are interesting structures with potential medicinal applications, and
Graphical Abstract
Figure 1: Biologically relevant 2-oxydibenzofuran-containing structures 1–6.
Figure 2: Representative bioactive structures containing benzofuro-fused pyridine analogues 7–9.
Scheme 1: Strategy for metal-free access to benzofuropyridine 13.
Scheme 2: Electrophilic aromatic substitution of 6-hydroxybenzofuro[2,3-b]pyridine (13).
Scheme 3: Synthesis of isomeric oxazole-fused derivatives.
Scheme 4: Fused derivatives from 16.
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
- important building blocks and ubiquitous scaffolds in many natural products and active pharmaceutical ingredients (API). Among various established methods, the Prins reaction has emerged as a powerful technique in the stereoselective synthesis of the tetrahydropyran skeleton with various substituents, and
- ; Prins cyclization; stereoselective; tetrahydropyran; Introduction 6-Membered saturated oxygen heterocycles, known as tetrahydropyran (THP), are recognized as privileged scaffolds, present in a variety of biologically important natural products, such as polyether antibiotics, marine toxins, pheromones
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 ...
Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects
- Shivani Gulati,
- Stephy Elza John and
- Nagula Shankaraiah
Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71
- well-thought-out as an important approach in medicinal chemistry and in drug discovery domains [91][92]. Purine scaffolds, such as allopurinol (106) used as the first choice of drug in gout therapy and temozolomide (107) used in the treatment of brain cancer are well-known examples [93][94]. Among the
- purine scaffolds, 5-aza-9-deazapurine and 5-azapurine have been identified as a favorable skeleton for the construction of new compounds such as 108 and 109 (Figure 8) [95][96]. Considering this fact, Dolzhenko and co-workers [97] reported the first microwave-assisted multicomponent strategy for the
- -alkylated pyridones are valuable scaffolds offering biological activity such as immunomodulators, memory-enhancers and anticancer agents [109][110]. A direct approach to achieve N-alkylated pyridones are less explored and those available present limitations such as poor selectivity and yields, expensive
Graphical Abstract
Figure 1: Marketed drugs with acridine moiety.
Scheme 1: Synthesis of 4-arylacridinediones.
Scheme 2: Proposed mechanism for acridinedione synthesis.
Scheme 3: Synthesis of tetrahydrodibenzoacridinones.
Scheme 4: Synthesis of naphthoacridines.
Scheme 5: Plausible mechanism for naphthoacridines.
Figure 2: Benzoazepines based potent molecules.
Scheme 6: Synthesis of azepinone.
Scheme 7: Proposed mechanism for azepinone formation.
Scheme 8: Synthesis of benzoazulenen-1-one derivatives.
Scheme 9: Proposed mechanism for benzoazulene-1-one synthesis.
Figure 3: Indole-containing pharmacologically active molecules.
Scheme 10: Synthesis of functionalized indoles.
Scheme 11: Plausible mechanism for the synthesis of functionalized indoles.
Scheme 12: Synthesis of spirooxindoles.
Scheme 13: Synthesis of substituted spirooxindoles.
Scheme 14: Plausible mechanism for the synthesis of substituted spirooxindoles.
Scheme 15: Synthesis of pyrrolidinyl spirooxindoles.
Scheme 16: Proposed mechanism for pyrrolidinyl spirooxindoles.
Figure 4: Pyran-containing biologically active molecules.
Scheme 17: Synthesis of functionalized benzopyrans.
Scheme 18: Plausible mechanism for synthesis of benzopyran.
Scheme 19: Synthesis of indoline-spiro-fused pyran derivatives.
Scheme 20: Proposed mechanism for indoline-spiro-fused pyran.
Scheme 21: Synthesis of substituted naphthopyrans.
Figure 5: Marketed drugs with pyrrole ring.
Scheme 22: Synthesis of tetra-substituted pyrroles.
Scheme 23: Mechanism for silica-supported PPA-SiO2-catalyzed pyrrole synthesis.
Scheme 24: Synthesis of pyrrolo[1,10]-phenanthrolines.
Scheme 25: Proposed mechanism for pyrrolo[1,10]-phenanthrolines.
Figure 6: Marketed drugs and molecules containing pyrimidine and pyrimidinones skeletons.
Scheme 26: MWA-MCR pyrimidinone synthesis.
Scheme 27: Two proposed mechanisms for pyrimidinone synthesis.
Scheme 28: MWA multicomponent synthesis of dihydropyrimidinones.
Scheme 29: Proposed mechanism for dihydropyrimidinones.
Figure 7: Biologically active fused pyrimidines.
Scheme 30: MWA- MCR for the synthesis of pyrrolo[2,3-d]pyrimidines.
Scheme 31: Proposed mechanism for pyrrolo[2,3-d]pyrimidines.
Scheme 32: Synthesis of substituted pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 33: Probable pathway for pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 34: Synthesis of pyridopyrimidines.
Scheme 35: Plausible mechanism for the synthesis of pyridopyrimidines.
Scheme 36: Synthesis of dihydropyridopyrimidine and dihydropyrazolopyridine.
Scheme 37: Proposed mechanism for the formation of dihydropyridopyrimidine.
Scheme 38: Synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 39: Plausible mechanism for the synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 40: Synthesis of decorated imidazopyrimidines.
Scheme 41: Proposed mechanism for imidazopyrimidine synthesis.
Figure 8: Pharmacologically active molecules containing purine bases.
Scheme 42: Synthesis of aza-adenines.
Scheme 43: Synthesis of 5-aza-7-deazapurines.
Scheme 44: Proposed mechanism for deazapurines synthesis.
Figure 9: Biologically active molecules containing pyridine moiety.
Scheme 45: Synthesis of steroidal pyridines.
Scheme 46: Proposed mechanism for steroidal pyridine.
Scheme 47: Synthesis of N-alkylated 2-pyridones.
Scheme 48: Two possible mechanisms for pyridone synthesis.
Scheme 49: Synthesis of pyridone derivatives.
Scheme 50: Postulated mechanism for synthesis of pyridone.
Figure 10: Biologically active fused pyridines.
Scheme 51: Benzimidazole-imidazo[1,2-a]pyridines synthesis.
Scheme 52: Mechanism for the synthesis of benzimidazole-imidazo[1,2-a]pyridines.
Scheme 53: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives.
Scheme 54: Proposed mechanism for spiro-pyridines.
Scheme 55: Functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 56: Mechanism postulated for macrocyclane-fused pyrazolo[3,4-b]pyridine.
Scheme 57: Generation of pyrazolo[3,4-b]pyridines.
Scheme 58: Proposed mechanism for the synthesis of pyrazolo[3,4-b]pyridines.
Scheme 59: Proposed mechanism for the synthesis of azepinoindole.
Figure 11: Pharmaceutically important molecules with quinoline moiety.
Scheme 60: Povarov-mediated quinoline synthesis.
Scheme 61: Proposed mechanism for Povarov reaction.
Scheme 62: Synthesis of pyrazoloquinoline.
Scheme 63: Plausible mechanism for pyrazoloquinoline synthesis.
Figure 12: Quinazolinones as pharmacologically significant scaffolds.
Scheme 64: Four-component reaction for dihydroquinazolinone.
Scheme 65: Proposed mechanism for dihydroquinazolinones.
Scheme 66: Synthesis purine quinazolinone and PI3K-δ inhibitor.
Scheme 67: Synthesis of fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 68: Proposed mechanism for fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 69: On-water reaction for synthesis of thiazoloquinazolinone.
Scheme 70: Proposed mechanism for the thiazoloquinazolinone synthesis.
Scheme 71: β-Cyclodextrin-mediated synthesis of indoloquinazolinediones.
Scheme 72: Proposed mechanism for synthesis of indoloquinazolinediones.
Figure 13: Triazoles-containing marketted drugs and pharmacologically active molecules.
Scheme 73: Cu(I) DAPTA-catalyzed 1,2,3-triazole formation.
Scheme 74: Mechanism for Cu(I) DAPTA-catalyzed triazole formation.
Scheme 75: Synthesis of β-hydroxy-1,2,3-triazole.
Scheme 76: Proposed mechanism for synthesis of β-hydroxy-1,2,3-triazoles.
Scheme 77: Synthesis of bis-1,2,4-triazoles.
Scheme 78: Proposed mechanism for bis-1,2,4-triazoles synthesis.
Figure 14: Thiazole containing drugs.
Scheme 79: Synthesis of a substituted thiazole ring.
Scheme 80: Synthesis of pyrazolothiazoles.
Figure 15: Chromene containing drugs.
Scheme 81: Magnetic nanocatalyst-mediated aminochromene synthesis.
Scheme 82: Proposed mechanism for the synthesis of chromenes.
Synthetic reactions driven by electron-donor–acceptor (EDA) complexes
- Zhonglie Yang,
- Yutong Liu,
- Kun Cao,
- Xiaobin Zhang,
- Hezhong Jiang and
- Jiahong Li
Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67
- -functionalization of glycine derivatives. The construction of C–C bonds As a crucial element in the construction of various organic scaffolds, the formation of C–C bonds remains a hot topic in the field of synthetic organic chemistry. The conventional approaches of C–C-bond construction typically employ transition
Graphical Abstract
Scheme 1: The electron transfer process in EDA complexes.
Scheme 2: Synthesis of benzo[b]phosphorus oxide 3 initiated by an EDA complex.
Scheme 3: Mechanism of the synthesis of quinoxaline derivative 7.
Scheme 4: Synthesis of imidazole derivative 10 initiated by an EDA complex.
Scheme 5: Synthesis of sulfamoylation product 12 initiated by an EDA complex.
Scheme 6: Mechanism of the synthesis of sulfamoylation product 12.
Scheme 7: Synthesis of indole derivative 22 initiated by an EDA complex.
Scheme 8: Synthesis of perfluoroalkylated pyrimidines 26 initiated by an EDA complex.
Scheme 9: Synthesis of phenanthridine derivative 29 initiated by an EDA complex.
Scheme 10: Synthesis of cis-tetrahydroquinoline derivative 32 initiated by an EDA complex.
Scheme 11: Mechanism of the synthesis of cis-tetrahydroquinoline derivative 32.
Scheme 12: Synthesis of phenanthridine derivative 38 initiated by an EDA complex.
Scheme 13: Synthesis of spiropyrroline derivative 40 initiated by an EDA complex.
Scheme 14: Synthesis of benzothiazole derivative 43 initiated by an EDA complex.
Scheme 15: Synthesis of perfluoroalkyl-s-triazine derivative 45 initiated by an EDA complex.
Scheme 16: Synthesis of indoline derivative 47 initiated by an EDA complex.
Scheme 17: Mechanism of the synthesis of spirocyclic indoline derivative 47.
Scheme 18: Synthesis of cyclobutane product 50 initiated by an EDA complex.
Scheme 19: Mechanism of the synthesis of spirocyclic indoline derivative 50.
Scheme 20: Synthesis of 1,3-oxazolidine compound 59 initiated by an EDA complex.
Scheme 21: Synthesis of trifluoromethylated product 61 initiated by an EDA complex.
Scheme 22: Synthesis of indole alkylation product 64 initiated by an EDA complex.
Scheme 23: Synthesis of perfluoroalkylation product 67 initiated by an EDA complex.
Scheme 24: Synthesis of hydrotrifluoromethylated product 70 initiated by an EDA complex.
Scheme 25: Synthesis of β-trifluoromethylated alkyne product 71 initiated by an EDA complex.
Scheme 26: Mechanism of the synthesis of 2-phenylthiophene derivative 74.
Scheme 27: Synthesis of allylated product 80 initiated by an EDA complex.
Scheme 28: Synthesis of trifluoromethyl-substituted alkynyl product 84 initiated by an EDA complex.
Scheme 29: Synthesis of dearomatized fluoroalkylation product 86 initiated by an EDA complex.
Scheme 30: Mechanism of the synthesis of dearomatized fluoroalkylation product 86.
Scheme 31: Synthesis of C(sp3)–H allylation product 91 initiated by an EDA complex.
Scheme 32: Synthesis of perfluoroalkylation product 93 initiated by an EDA complex.
Scheme 33: Synthesis of spirocyclic indolene derivative 95 initiated by an EDA complex.
Scheme 34: Synthesis of perfluoroalkylation product 97 initiated by an EDA complex.
Scheme 35: Synthesis of alkylated indole derivative 100 initiated by an EDA complex.
Scheme 36: Mechanism of the synthesis of alkylated indole derivative 100.
Scheme 37: Synthesis of arylated oxidized indole derivative 108 initiated by an EDA complex.
Scheme 38: Synthesis of 4-ketoaldehyde derivative 111 initiated by an EDA complex.
Scheme 39: Mechanism of the synthesis of 4-ketoaldehyde derivative 111.
Scheme 40: Synthesis of perfluoroalkylated olefin 118 initiated by an EDA complex.
Scheme 41: Synthesis of alkylation product 121 initiated by an EDA complex.
Scheme 42: Synthesis of acylation product 123 initiated by an EDA complex.
Scheme 43: Mechanism of the synthesis of acylation product 123.
Scheme 44: Synthesis of trifluoromethylation product 126 initiated by an EDA complex.
Scheme 45: Synthesis of unnatural α-amino acid 129 initiated by an EDA complex.
Scheme 46: Synthesis of thioether derivative 132 initiated by an EDA complex.
Scheme 47: Synthesis of S-aryl dithiocarbamate product 135 initiated by an EDA complex.
Scheme 48: Mechanism of the synthesis of S-aryl dithiocarbamate product 135.
Scheme 49: Synthesis of thioether product 141 initiated by an EDA complex.
Scheme 50: Mechanism of the synthesis of borate product 144.
Scheme 51: Synthesis of boronation product 148 initiated by an EDA complex.
Scheme 52: Synthesis of boration product 151 initiated by an EDA complex.
Scheme 53: Synthesis of boronic acid ester derivative 154 initiated by an EDA complex.
Scheme 54: Synthesis of β-azide product 157 initiated by an EDA complex.
Scheme 55: Decarboxylation reaction initiated by an EDA complex.
Scheme 56: Synthesis of amidated product 162 initiated by an EDA complex.
Scheme 57: Synthesis of diethyl phenylphosphonate 165 initiated by an EDA complex.
Scheme 58: Mechanism of the synthesis of diethyl phenylphosphonate derivative 165.
Scheme 59: Synthesis of (Z)-2-iodovinyl phenyl ether 168 initiated by an EDA complex.
Scheme 60: Mechanism of the synthesis of (Z)-2-iodovinyl phenyl ether derivative 168.
Scheme 61: Dehalogenation reaction initiated by an EDA complex.
Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles
- Soumyaranjan Pati,
- Renata G. Almeida,
- Eufrânio N. da Silva Júnior and
- Irishi N. N. Namboothiri
Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66
- synthesis of new functionalized 1,2,3-triazoles. Keywords: azoles; cycloaddition; enones; heterocycles; 1,2,3-triazoles; Introduction 1,2,3-Triazoles are significant non-natural heterocyclic scaffolds with extensive applications in biochemistry, agrochemistry and materials chemistry [1][2][3][4][5]. This
- class of heterocycles presents important biological properties, such as antiviral, anti-inflammatory, antimicrobial etc. and are considered as key building blocks in pharmaceutical industry [6][7][8][9]. Thus, they marked their presence as prominent scaffolds in many drug molecules such as tazobactam
Graphical Abstract
Scheme 1: Synthesis, functionalization and applications of triazoles.
Scheme 2: The reaction was performed using 0.2 mmol N-tosyl-1,2,3-triazole 1 and 0.2 mmol of cyclohexyl-1,3-d...
Scheme 3: Control experiments.
Scheme 4: Mechanistic proposal for the formation of β-triazolylenones.
Figure 1: Nucleophilic addition to 5- and 6-membered cyclic tosyloxyenones.
α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams
- Mikhail K. Klychnikov,
- Radek Pohl,
- Ivana Císařová and
- Ullrich Jahn
Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58
- . Conclusion We developed a two-step methodology for the synthesis of diverse γ-lactam scaffolds. A tandem reaction combining nucleophilic epoxide opening by N-allylic silylacetamides, Brook rearrangement, and radical oxygenation serves for the preparation of N-allylic α-(aminoxy)-γ-(silyloxy)amides 9, which
Graphical Abstract
Figure 1: Selected alkaloids containing the pyrrolidone motif.
Scheme 1: A) Classical γ-lactam synthesis by atom transfer radical cyclizations; B) previously developed tand...
Figure 2: X-ray crystal structure of the major (2R,4S)-alkoxyamine hydrochloride derived from 9j. Displacemen...
Scheme 2: Formation of the α-(aminoxy)amides 9o,p.
Figure 3: X-ray crystal structure of the minor cis-diastereomers of the keto lactam 13j (left) and the hydrox...
Scheme 3: Thermal radical cyclization reactions of amides 9l–p bearing cyclic units. Conditions: a) t-BuOH, 1...
Scheme 4: Epimerization of spirolactams 12m,n.
Scheme 5: The Dess–Martin oxidation of lactams 12l–o. Conditions: a) DMP (1.3 equiv), t-BuOH (10 mol %), CH2Cl...
Scheme 6: Selected transformations of the lactams trans-12b and 12o.
Scheme 7: Diastereoselectivity for the formation of α-(aminoxy)amides 9i–k.
Scheme 8: Rationalization of the diastereoselectivity for the formation of the α-(aminoxy)amide 9l.
Scheme 9: Rationalization of the thermal radical cyclization diastereoselectivity of alkoxyamines 9a–k. (S)-C...
Scheme 10: The stereochemical course for the formation of products 12m,n by thermal radical cyclization of alk...
Scheme 11: Formation of bicycles 12o,p.
Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines
- Geetanjali S. Sontakke,
- Rahul K. Shukla and
- Chandra M. R. Volla
Beilstein J. Org. Chem. 2021, 17, 485–493, doi:10.3762/bjoc.17.42
- -aminoquinoline motif are shown in Figure 1 [46][47]. As a result, a variety of transition metal-catalyzed C2-selective aminations of azine N-oxides were explored extensively [28][29][30][31][32][33][34]. Additionally, various transition metal-free C2-aminations of these scaffolds were also investigated [35][36
- scaffolds. The late-stage modification of natural products is the salient feature of this current transformation. Experimental General procedure for the C2-selective synthesis of α-triazolylquinolines 3 To an oven-dried reaction tube equipped with a magnetic stirring bar were added quinoline N-oxide (1a, 29
Graphical Abstract
Figure 1: Bioactive molecules containing the 2-aminoquinoline motif.
Scheme 1: C2-selective C–N bond formation of N-oxides.
Scheme 2: Substrate scope of N-sulfonyl-1,2,3-triazoles. Reaction conditions: 1a (0.2 mmol), 2 (0.24 mmol) an...
Scheme 3: Substrate scope of quinoline N-oxides. Reaction conditions: 1 (0.2 mmol), 2a (0.24 mmol) and DCE (2...
Scheme 4: Late-stage modification of natural products.
Scheme 5: Substrate scope for the reaction of substituted triazoles with isoquinoline N-oxide.
Scheme 6: Gram-scale and one-pot synthesis.
Scheme 7: Proposed mechanism.
Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement
- Vladimir Kubyshkin,
- Rebecca Davis and
- Nediljko Budisa
Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40
Graphical Abstract
Figure 1: The structures of the fluoroprolines discussed herein.
Figure 2: The distinction between “the alanine and the proline worlds”. While the polyalanine backbone leads ...
Figure 3: Molecular volume for 20 coded amino acids and fluoroprolines. The COSMO volume was calculated for a...
Figure 4: Comparative analysis of the electrostatic potential for proline and fluoroprolines (electrostatic p...
Figure 5: Experimental logP data for methyl esters of N-acetylamino acids.
Figure 6: The conformational dependence of the proline ring on the fluorination at position 4.
Figure 7: Rotation around the peptidyl-prolyl fragments in polypeptide structures is important for correct ov...
Figure 8: The complex fate of a protein-encoded amino acid in the cell (EF-Tu – elongation factor thermo unst...
Figure 9: Metabolic routes for proline in E. coli. A) Synthesis of proline and B) degradation of proline.
Figure 10: A complete flowchart for the proline incorporation into proteins during ribosomal biosynthesis. A) ...
Figure 11: Amide bond formation capacities of fluoroprolines compared to some coded amino acids measured on ri...
Figure 12: Ribbon representation of the X-ray crystal structures of proteins containing fluoroprolines. A) Enh...
Figure 13: Problems and phenomena associated with the production of a protein-containing proline-to-fluoroprol...
Figure 14: Effects of fluoroprolines on recombinant protein expression using the auxotrophic expression host E...
Figure 15: A) Experimental setup for the incorporation of fluoroprolines into proteins. B) Adaptive laboratory...
CF3-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry
- Anthony J. Fernandes,
- Armen Panossian,
- Bastien Michelet,
- Agnès Martin-Mingot,
- Frédéric R. Leroux and
- Sébastien Thibaudeau
Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32
- cations is probably the α-(trifluoromethyl) carbocation. Many efforts are currently devoted to develop methods allowing the efficient insertion of fluorine atoms or fluorinated groups into organic molecules [7][8][9][10][11][12]. The increasing demand for fluorinated scaffolds, due to the striking
Graphical Abstract
Figure 1: Stabilizing interaction in the CF3CH2+ carbenium ion (top) and structure of the first observable fl...
Scheme 1: Isodesmic equations accounting for the destabilizing effect of the CF3 group. ΔE in kcal⋅mol−1, cal...
Scheme 2: Stabilizing effect of fluorine atoms by resonance electron donation in carbenium ions (δ in ppm).
Scheme 3: Direct in situ NMR observation of α-(trifluoromethyl)carbenium ion or protonated alcohols. Δδ = δ19...
Scheme 4: Reported 13C NMR chemical shifts for the α-(trifluoromethyl)carbenium ion 10c (δ in ppm).
Scheme 5: Direct NMR observation of α-(trifluoromethyl)carbenium ions in situ (δ in ppm).
Scheme 6: Illustration of the ion pair solvolysis mechanism for sulfonate 13f. YOH = solvent.
Figure 2: Solvolysis rate for 13a–i and 17.
Figure 3: Structures of allyl triflates 18 and 19 and allyl brosylate 20. Bs = p-BrC6H4SO2.
Figure 4: Structure of tosylate derivatives 21.
Figure 5: a) Structure of triflate derivatives 22. b) Stereochemistry outcomes of the reaction starting from (...
Scheme 7: Solvolysis reaction of naphthalene and anthracenyl derivatives 26 and 29.
Figure 6: Structure of bisarylated derivatives 34.
Figure 7: Structure of bisarylated derivatives 36.
Scheme 8: Reactivity of 9c in the presence of a Brønsted acid.
Scheme 9: Cationic electrocyclization of 38a–c under strongly acidic conditions.
Scheme 10: Brønsted acid-catalyzed synthesis of indenes 42 and indanes 43.
Scheme 11: Reactivity of sulfurane 44 in triflic acid.
Scheme 12: Solvolysis of triflate 45f in alcoholic solvents.
Scheme 13: Synthesis of labeled 18O-52.
Scheme 14: Reactivity of sulfurane 53 in triflic acid.
Figure 8: Structure of tosylates 56 and 21f.
Scheme 15: Resonance forms in benzylic carbenium ions.
Figure 9: Structure of pyrrole derivatives 58 and 59.
Scheme 16: Resonance structure 60↔60’.
Scheme 17: Ga(OTf)3-catalyzed synthesis of 3,3’- and 3,6’-bis(indolyl)methane from trifluoromethylated 3-indol...
Scheme 18: Proposed reaction mechanism.
Scheme 19: Metal-free 1,2-phosphorylation of 3-indolylmethanols.
Scheme 20: Superacid-mediated arylation of thiophene derivatives.
Scheme 21: In situ mechanistic NMR investigations.
Scheme 22: Proposed mechanisms for the prenyltransferase-catalyzed condensation.
Scheme 23: Influence of a CF3 group on the allylic SN1- and SN2-mechanism-based reactions.
Scheme 24: Influence of the CF3 group on the condensation reaction.
Scheme 25: Solvolysis of 90 in TFE.
Scheme 26: Solvolysis of allyl triflates 94 and 97 and isomerization attempt of 96.
Scheme 27: Proposed mechanism for the formation of 95.
Scheme 28: Formation of α-(trifluoromethyl)allylcarbenium ion 100 in a superacid.
Scheme 29: Lewis acid activation of CF3-substituted allylic alcohols.
Scheme 30: Bimetallic-cluster-stabilized α-(trifluoromethyl)carbenium ions.
Scheme 31: Reactivity of cluster-stabilized α-(trifluoromethyl)carbenium ions.
Scheme 32: α-(Trifluoromethyl)propargylium ion 122↔122’ generated from silyl ether 120 in a superacid.
Scheme 33: Formation of α-(trifluoromethyl)propargylium ions from CF3-substituted propargyl alcohols.
Scheme 34: Direct NMR observation of the protonation of some trifluoromethyl ketones in situ and the correspon...
Scheme 35: Selected resonance forms in protonated fluoroketone derivatives.
Scheme 36: Acid-catalyzed Friedel–Crafts reactions of trifluoromethyl ketones 143a,b and 147a–c.
Scheme 37: Enantioselective hydroarylation of CF3-substituted ketones.
Scheme 38: Acid-catalyzed arylation of ketones 152a–c.
Scheme 39: Reactivity of 156 in a superacid.
Scheme 40: Reactivity of α-CF3-substituted heteroaromatic ketones and alcohols as well as 1,3-diketones.
Scheme 41: Reactivity of 168 with benzene in the presence of a Lewis or Brønsted acid.
Scheme 42: Acid-catalyzed three-component asymmetric reaction.
Scheme 43: Anodic oxidation of amines 178a–c and proposed mechanism.
Scheme 44: Reactivity of 179b in the presence of a strong Lewis acid.
Scheme 45: Trifluoromethylated derivatives as precursors of trifluoromethylated iminium ions.
Scheme 46: Mannich reaction with trifluoromethylated hemiaminal 189.
Scheme 47: Suitable nucleophiles reacting with 192 after Lewis acid activation.
Scheme 48: Strecker reaction involving the trifluoromethylated iminium ion 187.
Scheme 49: Reactivity of 199 toward nucleophiles.
Scheme 50: Reactivity of 204a with benzene in the presence of a Lewis acid.
Scheme 51: Reactivity of α-(trifluoromethyl)-α-chloro sulfides in the presence of strong Lewis acids.
Scheme 52: Anodic oxidation of sulfides 213a–h and Pummerer rearrangement.
Scheme 53: Mechanism for the electrochemical oxidation of the sulfide 213a.
Scheme 54: Reactivity of (trifluoromethyl)diazomethane (217a) in HSO3F.
Figure 10: a) Structure of diazoalkanes 217a–c and b) rate-limiting steps of their decomposition.
Scheme 55: Deamination reaction of racemic 221 and enantioenriched (S)-221.
Scheme 56: Deamination reaction of labeled 221-d2. Elimination products were formed in this reaction, the yiel...
Scheme 57: Deamination reaction of 225-d2. Elimination products were also formed in this reaction in undetermi...
Scheme 58: Formation of 229 from 228 via 1,2-H-shift.
Scheme 59: Deamination reaction of 230. Elimination products were formed in this reaction, the yield of which ...
Scheme 60: Deamination of several diazonium ions. Elimination products were formed in these reactions, the yie...
Scheme 61: Solvolysis reaction mechanism of alkyl tosylates.
Scheme 62: Solvolysis outcome for the tosylates 248 and 249 in HSO3FSbF5.
Figure 11: Solvolysis rate of 248, 249, 252, and 253 in 91% H2SO4.
Scheme 63: Illustration of the reaction pathways. TsCl, pyridine, −5 °C (A); 98% H2SO4, 30 °C (B); 98% H2SO4, ...
Scheme 64: Proposed solvolysis mechanism for the aliphatic tosylate 248.
Scheme 65: Solvolysis of the derivatives 259 and 260.
Scheme 66: Solvolysis of triflate 261. SOH = solvent.
Scheme 67: Intramolecular Friedel–Crafts alkylations upon the solvolysis of triflates 264 and 267.
Scheme 68: α-CF3-enhanced γ-silyl elimination of cyclobutyltosylates 270a,b.
Scheme 69: γ-Silyl elimination in the synthesis of a large variety of CF3-substituted cyclopropanes. Pf = pent...
Scheme 70: Synthetic pathways to 281. aNMR yields.
Scheme 71: The cyclopropyl-substituted homoallylcyclobutylcarbenium ion manifold.
Scheme 72: Reactivity of CF3-substituted cyclopropylcarbinyl derivatives 287a–c. LG = leaving group.
Scheme 73: Reactivity of CF3-substituted cyclopropylcarbinyl derivatives 291a–c.
Scheme 74: Superacid-promoted dimerization or TFP.
Scheme 75: Reactivity of TFP in a superacid.
Scheme 76: gem-Difluorination of α-fluoroalkyl styrenes via the formation of a “hidden” α-RF-substituted carbe...
Scheme 77: Solvolysis of CF3-substituted pentyne 307.
Scheme 78: Photochemical rearrangement of 313.
Figure 12: Structure of 2-norbornylcarbenium ion 318 and argued model for the stabilization of this cation.
Figure 13: Structures and solvolysis rate (TFE, 25 °C) of the sulfonates 319–321. Mos = p-MeOC6H4SO2.
Scheme 79: Mechanism for the solvolysis of 323. SOH = solvent.
Scheme 80: Products formed by the hydrolysis of 328.
Scheme 81: Proposed carbenium ion intermediates in an equilibrium during the solvolysis of tosylates 328, 333,...
Hydrazides in the reaction with hydroxypyrrolines: less nucleophilicity – more diversity
- Dmitrii A. Shabalin,
- Evgeniya E. Ivanova,
- Igor A. Ushakov,
- Elena Yu. Schmidt and
- Boris A. Trofimov
Beilstein J. Org. Chem. 2021, 17, 319–324, doi:10.3762/bjoc.17.29
- synthesis of three types of highly functionalized azaheterocyclic scaffolds (dihydropyridazines, tetrahydropyridazines, and partially saturated tricyclic systems) from readily available hydroxypyrrolines and hydrazides are described. The directions of the transformation of a common initial intermediate
- saturated pyridazine scaffolds is both highly topical and necessary. Recently, we have developed a convenient approach to the 1,4-dihydropyridazine core based on the Brønsted acid-catalyzed regioselective recyclization of 5-hydroxypyrrolines (assembled in a one-pot manner from ketoximes and acetylene gas [8
- nucleophilicity of the hydrazides diversifies the recyclization of 5-hydroxypyrrolines and results in the chemoselective formation of highly functionalized azaheterocyclic scaffolds. Such a short-cut to partially saturated azaheterocyclic scaffolds meets the interests of modern medicinal chemistry which today
Graphical Abstract
Figure 1: Biologically active di- and tetrahydropyridazines.
Scheme 1: Recyclization of hydroxypyrrolines with hydrazine derivatives.
Scheme 2: Synthesis of tetrahydropyridazines 3.
Scheme 3: Synthesis of dihydropyridazines 4.
Scheme 4: Recyclization of hydroxypyrroline 1a with hydrazides 2d and 2e.
Scheme 5: A proposed mechanism for the recyclization of hydroxypyrrolines 1 with hydrazides 2.
The preparation and properties of 1,1-difluorocyclopropane derivatives
- Kymbat S. Adekenova,
- Peter B. Wyatt and
- Sergazy M. Adekenov
Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25
- . presented a practical method to synthesize monofluorinated allylic scaffolds via a Pd-catalyzed C–C activation/C–F cleavage (Scheme 69) [119]. This ring opening of the gem-difluorocyclopropanes 161 occurred with both O- and N-nucleophiles. The resulting 2-fluorinated allylic products 162 were obtained in
Graphical Abstract
Scheme 1: Synthesis of 1,1-difluoro-2,3-dimethylcyclopropane (2).
Scheme 2: Cyclopropanation via dehydrohalogenation of chlorodifluoromethane.
Scheme 3: Difluorocyclopropanation of methylstyrene 7 using dibromodifluoromethane and zinc.
Scheme 4: Synthesis of difluorocyclopropanes from the reaction of dibromodifluoromethane and triphenylphosphi...
Scheme 5: Generation of difluorocarbene in a catalytic two-phase system and its addition to tetramethylethyle...
Scheme 6: The reaction of methylstyrene 7 with chlorodifluoromethane (11) in the presence of a tetraarylarson...
Scheme 7: Pyrolysis of sodium chlorodifluoroacetate (12) in refluxing diglyme in the presence of alkene 13.
Scheme 8: Synthesis of boron-substituted gem-difluorocyclopropanes 16.
Scheme 9: Addition of sodium bromodifluoroacetate (17) to alkenes.
Scheme 10: Addition of sodium bromodifluoroacetate (17) to silyloxy-substituted cyclopropanes 20.
Scheme 11: Synthesis of difluorinated nucleosides.
Scheme 12: Addition of butyl acrylate (26) to difluorocarbene generated from TFDA (25).
Scheme 13: Addition of difluorocarbene to propargyl esters 27 and conversion of the difluorocyclopropenes 28 t...
Scheme 14: The generation of difluorocyclopropanes using MDFA 30.
Scheme 15: gem-Difluorocyclopropanation of styrene (32) using difluorocarbene generated from TMSCF3 (31) under...
Scheme 16: Synthesis of a gem-difluorocyclopropane derivative using HFPO (41) as a source of difluorocarbene.
Scheme 17: Cyclopropanation of (Z)-2-butene in the presence of difluorodiazirine (44).
Scheme 18: The cyclopropanation of 1-octene (46) using Seyferth's reagent (45) as a source of difluorocarbene.
Scheme 19: Alternative approaches for the difluorocarbene synthesis from trimethyl(trifluoromethyl)tin (48).
Scheme 20: Difluorocyclopropanation of cyclohexene (49).
Scheme 21: Synthesis of difluorocyclopropane derivative 53 using bis(trifluoromethyl)cadmium (51) as the diflu...
Scheme 22: Addition of difluorocarbene generated from tris(trifluoromethyl)bismuth (54).
Scheme 23: Addition of a stable (trifluoromethyl)zinc reagent to styrenes.
Scheme 24: The preparation of 2,2-difluorocyclopropanecarboxylic acids of type 58.
Scheme 25: Difluorocyclopropanation via Michael cyclization.
Scheme 26: Difluorocyclopropanation using N-acylimidazolidinone 60.
Scheme 27: Difluorocyclopropanation through the cyclization of phenylacetonitrile (61) and 1,2-dibromo-1,1-dif...
Scheme 28: gem-Difluoroolefins 64 for the synthesis of functionalized cyclopropanes 65.
Scheme 29: Preparation of aminocyclopropanes 70.
Scheme 30: Synthesis of fluorinated methylenecyclopropane 74 via selenoxide elimination.
Scheme 31: Reductive dehalogenation of (1R,3R)-75.
Scheme 32: Synthesis of chiral monoacetates by lipase catalysis.
Scheme 33: Transformation of (±)-trans-81 using Rhodococcus sp. AJ270.
Scheme 34: Transformation of (±)-trans-83 using Rhodococcus sp. AJ270.
Scheme 35: Hydrogenation of difluorocyclopropenes through enantioselective hydrocupration.
Scheme 36: Enantioselective transfer hydrogenation of difluorocyclopropenes with a Ru-based catalyst.
Scheme 37: The thermal transformation of trans-1,2-dichloro-3,3-difluorocyclopropane (84).
Scheme 38: cis–trans-Epimerization of 1,1-difluoro-2,3-dimethylcyclopropane.
Scheme 39: 2,2-Difluorotrimethylene diradical intermediate.
Scheme 40: Ring opening of stereoisomers 88 and 89.
Scheme 41: [1,3]-Rearrangement of alkenylcyclopropanes 90–92.
Scheme 42: Thermolytic rearrangement of 2,2-difluoro-1-vinylcyclopropane (90).
Scheme 43: Thermal rearrangement for ethyl 3-(2,2-difluoro)-3-phenylcyclopropyl)acrylates 93 and 95.
Scheme 44: Possible pathways of the ring opening of 1,1-difluoro-2-vinylcyclopropane.
Scheme 45: Equilibrium between 1,1-difluoro-2-methylenecyclopropane (96) and (difluoromethylene)cyclopropane 97...
Scheme 46: Ring opening of substituted 1,1-difluoro-2,2-dimethyl-3-methylenecyclopropane 98.
Scheme 47: 1,1-Difluorospiropentane rearrangement.
Scheme 48: Acetolysis of (2,2-difluorocyclopropyl)methyl tosylate (104) and (1,1-difluoro-2-methylcyclopropyl)...
Scheme 49: Ring opening of gem-difluorocyclopropyl ketones 106 and 108 by thiolate nucleophiles.
Scheme 50: Hydrolysis of gem-difluorocyclopropyl acetals 110.
Scheme 51: Ring-opening reaction of 2,2-difluorocyclopropyl ketones 113 in the presence of ionic liquid as a s...
Scheme 52: Ring opening of gem-difluorocyclopropyl ketones 113a by MgI2-initiated reaction with diarylimines 1...
Scheme 53: Ring-opening reaction of gem-difluorocyclopropylstannanes 117.
Scheme 54: Preparation of 1-fluorovinyl vinyl ketone 123 and the synthesis of 2-fluorocyclopentenone 124. TBAT...
Scheme 55: Iodine atom-transfer ring opening of 1,1-difluoro-2-(1-iodoalkyl)cyclopropanes 125a–c.
Scheme 56: Ring opening of bromomethyl gem-difluorocyclopropanes 130 and formation of gem-difluoromethylene-co...
Scheme 57: Ring-opening aerobic oxidation reaction of gem-difluorocyclopropanes 132.
Scheme 58: Dibrominative ring-opening functionalization of gem-difluorocyclopropanes 134.
Scheme 59: The selective formation of (E,E)- and (E,Z)-fluorodienals 136 and 137 from difluorocyclopropyl acet...
Scheme 60: Proposed mechanism for the reaction of difluoro(methylene)cyclopropane 139 with Br2.
Scheme 61: Thermal rearrangement of F2MCP 139 and iodine by CuI catalysis.
Scheme 62: Synthesis of 2-fluoropyrroles 142.
Scheme 63: Ring opening of gem-difluorocyclopropyl ketones 143 mediated by BX3.
Scheme 64: Lewis acid-promoted ring-opening reaction of 2,2-difluorocyclopropanecarbonyl chloride (148).
Scheme 65: Ring-opening reaction of the gem-difluorocyclopropyl ketone 106 by methanolic KOH.
Scheme 66: Hydrogenolysis of 1,1-difluoro-3-methyl-2-phenylcyclopropane (151).
Scheme 67: Synthesis of monofluoroalkenes 157.
Scheme 68: The stereoselective Ag-catalyzed defluorinative ring-opening diarylation of 1-trimethylsiloxy-2,2-d...
Scheme 69: Synthesis of 2-fluorinated allylic compounds 162.
Scheme 70: Pd-catalyzed cross-coupling reactions of gem-difluorinated cyclopropanes 161.
Scheme 71: The (Z)-selective Pd-catalyzed ring-opening sulfonylation of 2-(2,2-difluorocyclopropyl)naphthalene...
Figure 1: Structures of zosuquidar hydrochloride and PF-06700841.
Scheme 72: Synthesis of methylene-gem-difluorocyclopropane analogs of nucleosides.
Figure 2: Anthracene-difluorocyclopropane hybrid derivatives.
Figure 3: Further examples of difluorcyclopropanes in modern drug discovery.
Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders
- David Straßburger,
- Svenja Herziger,
- Katharina Huth,
- Moritz Urschbach,
- Rainer Haag and
- Pol Besenius
Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10
- polymers as a promising class of synthetic scaffolds [10][11][12][13][14]. Supramolecular polymers do provide additional features like a high degree of flexibility and excellent adaptivity, which are critical in biological interactions [15]. As water is the dominant solvent in biological systems, aqueous
Graphical Abstract
Scheme 1: The synthesis of the C3-symmetrical tetraethylene glycol-decorated peptide amphiphile I and the azi...
Scheme 2: Synthesis of the sulfated peptide amphiphile II by copper-catalyzed azide–alkyne cyclization.
Figure 1: Analysis of the self-assembly behavior of I by A: CD-spectra of 5, 10, 25 or 50 µM aqueous solution...
Figure 2: Analysis of the supramolecular polymerization of II by A: CD-spectra of a 25 µM solution in TRIS bu...
Figure 3: Concentration-dependent relative L-selectin binding of the supramolecular polymers I and II in HEPE...
Molecular basis for protein–protein interactions
- Brandon Charles Seychell and
- Tobias Beck
Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1
- initial capsid formation is limited due to the time required for an intermediate steady state for the consequent assembly. These mathematical calculations and generalisations, however, do not take into consideration biological scaffolds, such as nucleic acids, which can facilitate or disrupt the capsid
- that a nucleic acid scaffold aids the assembly by concentrating assembly units and providing additional association energy. Some viral capsids can self-assemble around other scaffolds that mimic the viral genome in charge and size [89] or can also assemble without any scaffold to form empty capsid
- containers [90]. CCMV was the first icosahedral viral capsid to be disassembled and reassembled in vitro [91]. The CCMV capsid can be reassembled into empty capsids as well as into different conformations, such as disks, rods, tubes, and multiwalled capsids by using different scaffolds [92]. In these cases
Graphical Abstract
Figure 1: Different methodologies employed to study PPIs. The protein used for illustration is the heterodime...
Figure 2: Mechanisms of homooligomeric complex formations. a) Domain swapping of RNase A (PDB: 1A2W) [73]. The sw...
Figure 3: Parts a) and b) represent the electron densities and B-factors of TMV, respectively. The cryo-EM st...
Figure 4: Schematic of the general assembly of charged protein containers to form binary nanoparticle superla...
All-carbon [3 + 2] cycloaddition in natural product synthesis
- Zhuo Wang and
- Junyang Liu
Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251
- quaternary stereocenters (Scheme 7). We believe that the enantioselective all-carbon [3 + 2] cycloaddition provides a new strategy for the preparation of sp3-carbon-enriched complex scaffolds [81][82] for biological studies and potential new drug development. The all-carbon [3 + 2] cycloaddition is
Graphical Abstract
Figure 1: Highly-substituted five-membered carbocycle in biologically significant natural products.
Figure 2: Natural product synthesis featuring the all-carbon [3 + 2] cycloaddition. (Quaternary carbon center...
Scheme 1: Representative natural product syntheses that feature the all-carbon [3 + 2] cyclization as the key...
Scheme 2: (A) An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition with allenyl diazo compound 38...
Scheme 3: (A) Palladium-catalyzed intermolecular carboxylative TMM cycloaddition [36]. (B) The proposed mechanism....
Scheme 4: Natural product syntheses that make use of palladium-catalyzed intermolecular [3 + 2] cycloaddition...
Scheme 5: (A) Phosphine-catalyzed [3 + 2] cycloaddition [17]. (B) The proposed mechanism.
Scheme 6: Lu’s [3 + 2] cycloaddition in natural product synthesis. (A) Synthesis of longeracinphyllin A (10) [41]...
Scheme 7: (A) Phosphine-catalyzed [3 + 2] annulation of unsymmetric isoindigo 100 with allene in the preparat...
Scheme 8: (A) Rhodium-catalyzed intracmolecular [3 + 2] cycloaddition [49]. (B) The proposed catalytic cycle of t...
Scheme 9: Total synthesis of natural products reported by Yang and co-workers applying rhodium-catalyzed intr...
Scheme 10: (A) Platinum(II)-catalyzed intermolecular [3 + 2] cycloaddition of propargyl ether 139 and n-butyl ...
Scheme 11: (A) Platinum-catalyzed intramolecular [3 + 2] cycloaddition of propargylic ketal derivative 142 to ...
Scheme 12: (A) Synthesis of phyllocladanol (21) features a Lewis acid-catalyzed formal intramolecular [3 + 2] ...
Scheme 13: The recent advances of [3 + 2] annulation in natural product synthesis. (A) The preparation of melo...
Selected peptide-based fluorescent probes for biological applications
- Debabrata Maity
Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247
- for biomolecule detection [27][28]. Being intrinsically modular, peptide scaffolds also allow the attachment of multiple fluorophores simultaneously [29]. It provides the opportunity of developing ratiometric fluorescent sensors from the interaction between multiple fluorophores (Figure 1B
Graphical Abstract
Figure 1: Three different type of peptide-based fluorescent probes and their interaction with nucleic acids a...
Figure 2: A) Molecular structure of peptidic probe 1, Inset: HeLa cells incubated with peptide 1 (50 μM), sho...
Figure 3: A) Molecular structure of probe 2; B) fluorescence emission spectra for the titration of a 10 μM so...
Figure 4: A) Molecular structure of 3; B) fluorescence emission spectra for the titration of a 10 μM solution...
Figure 5: A) Molecular structure of 4 and 5; B) fluorescence spectra for the titration of a 0.5 μM solution o...
Figure 6: A) Molecular structure of 6; B) possible binding mode of pyrene termini of 6 to CB[8] according to ...
Figure 7: A) Molecular structure of peptidic probes 7 and 8; B) fluorescence emission spectra of probe 7 (5.0...
Figure 8: Top: Molecular structure of 9; bottom: A) fluorescence response of 9 (500 nM) upon addition of β-tr...
Figure 9: Top: Molecular structures of 10 and 11; bottom: A) fluorescence emission spectra of 10 (1.0 µM, λex...
Figure 10: A) Structure of two peptide amphiphiles 12 and 13; B) fluorescent spectra (λex = 400 nm) from a tit...
Figure 11: a) Molecular structure of peptide 14; b) the coordinate represents the states of sensor at differen...
Three-component reactions of aromatic amines, 1,3-dicarbonyl compounds, and α-bromoacetaldehyde acetal to access N-(hetero)aryl-4,5-unsubstituted pyrroles
- Wenbo Huang,
- Kaimei Wang,
- Ping Liu,
- Minghao Li,
- Shaoyong Ke and
- Yanlong Gu
Beilstein J. Org. Chem. 2020, 16, 2920–2928, doi:10.3762/bjoc.16.241
- -bromoacetaldehyde acetal by using aluminum(III) chloride as a Lewis acid catalyst through [1 + 2 + 2] annulation. This new versatile methodology provides a wide scope for the synthesis of different functional N-(hetero)aryl-4,5-unsubstituted pyrrole scaffolds, which can be further derived to access multisubstituted
- ][18] are some of the commonly used approaches for the construction of pyrrole scaffolds. Additionally, the biocatalytic synthesis of substituted pyrroles was also developed [19]. Though sustained efforts have been achieved to develop efficient synthetic methods for the preparation of this structural
- , the transformations can generally be realized through the following three approaches (Scheme 1): (i) [1 + 1 + 3] annulation, in which (hetero)arylamines are reacted with a C3 donor and a C1 donor to construct pyrrole scaffolds. Kumar et al. [26] developed a proline-catalyzed Mannich reaction
Graphical Abstract
Figure 1: Representative biologically active N-(hetero)aryl-4,5-unsubstituted pyrrole scaffolds.
Scheme 1: Typical routes to N-(heteroaryl)-4,5-unsubstituted pyrroles.
Scheme 2: Substrate scope of the pyrrole synthesis.
Scheme 3: Synthesis of N-heterocyclic pyrroles.
Scheme 4: Direct synthesis of pyrrole-3-carboxamide derivatives.
Scheme 5: Plausible mechanism of the three-component reaction.
Scheme 6: Synthesis of polysubstituted pyrazolo[3,4-b]pyridine derivatives.
Synthesis of imidazo[1,5-a]pyridines via cyclocondensation of 2-(aminomethyl)pyridines with electrophilically activated nitroalkanes
- Dmitrii A. Aksenov,
- Nikolai A. Arutiunov,
- Vladimir V. Maliuga,
- Alexander V. Aksenov and
- Michael Rubin
Beilstein J. Org. Chem. 2020, 16, 2903–2910, doi:10.3762/bjoc.16.239
- imidazo[1,5-a]pyridine core is also considered to be one of the privileged pharmacophoric scaffolds and can be found in many biologically active compounds, for example, the potent antitumor agent C 1311 inhibiting topoisomerase II [4][5][6][7][8][9] or pirmagrel, a cytotoxic immunosuppressant and DNA
Graphical Abstract
Figure 1: Biologically active imidazo[1,5-a]pyridines.
Scheme 1: Activation of nitroalkanes towards nucleophilic attack by amines.
Scheme 2: Mechanistic rationale.
Scheme 3: Reaction of the N-tosylate 17 with electrophilic nitroalkanes.
Scheme 4: Reaction of 2-(aminomethyl)pyridine (12) with electrophilic nitroalkanes.
Scheme 5: Reaction of the 2-(aminomethyl)quinolines 18 with electrophilic nitroalkanes.
Scheme 6: Reactivity of α-nitroacetophenone (1h) and α-nitroacetic ester (1i).
Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes
- Lena Reinke,
- Julia Bartl,
- Marcus Koch and
- Stefan Kubik
Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219
- receptors based on other scaffolds [22][23][24][25]. To test whether this binding motif induces AuNP crosslinking, we synthesized nanoparticles containing peripheral zinc(II)–DPA complexes together with a solubilizing triethylene glycol-based ligand in different ratios and studied their interaction with
Graphical Abstract
Figure 1: Schematic illustration of the analyte-induced crosslinking of gold nanoparticles containing a mixtu...
Scheme 1: Syntheses of the ligands rac-1 and (R)-1. Conditions: i) TsCl, NaOH, THF, 0 °C, 60 min → 25 °C, 80 ...
Scheme 2: Synthesis of ligand 2. Conditions: i) potassium phthalimide, DMF, 25 °C, 18 h, 67%; ii) 2,2'-dipico...
Figure 2: Photographs of solutions of NPrac-1 in water (0.25 mg/mL) containing different sodium salts at a co...
Figure 3: Sections of the 1H NMR spectra of solutions of NP25 in D2O/CD3OD 1:2 (v/v) between 8.9 and 3.9 ppm ...
Figure 4: Images of vials containing solutions of NP10-Zn (0.25 mg/mL) in water/methanol 1:2 (v/v) and additi...
Figure 5: Photograph of the solutions of the competition experiment. Vial (a) only contained NP10-Zn (and the...
Figure 6: UV–vis spectra of NP10-Zn (0.25 mg/mL in the initial measurement) in water/methanol 1:2 (v/v) conta...
Figure 7: TEM images of NP10-Zn (0.25 mg/mL) in water/methanol 1:2 (v/v) before (a) and after the addition of...
Synthesis of novel fluorinated building blocks via halofluorination and related reactions
- Attila Márió Remete,
- Tamás T. Novák,
- Melinda Nonn,
- Matti Haukka,
- Ferenc Fülöp and
- Loránd Kiss
Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208
- uncovered, too. The oxidation of (rac)-31 under basic conditions delivered the conjugated diene (rac)-34, possibly through a deselenation/E1cB elimination sequence similar to the one shown in Scheme 22. Conclusion In conclusion, novel fluorine-containing, functionalized small-molecular scaffolds have been
Graphical Abstract
Scheme 1: Proposed outcome of the halofluorination of (rac)-1. Only the main conformers of (rac)-1 and (rac)-...
Scheme 2: Halofluorination reactions of the trans-diester (rac)-1.
Scheme 3: Probable outcomes of the halofluorination of 4. Both conformers of the compounds 4, (rac)-T2a,b, an...
Scheme 4: Halofluorination reactions of the cis-diester 4. Important NOESY interactions are indicated by two-...
Scheme 5: Halofluorination reactions of the cis-tetrahydrophthalic imide derivative 7.
Scheme 6: Synthesis and halofluorination of the trans-imide (rac)-10.
Figure 1: Crystal structure of (rac)-11b.
Scheme 7: Synthesis of the cyclic carbamide (rac)-13.
Scheme 8: Halofluorination reactions of the γ-lactam (rac)-14. Relevant NOESY interactions are indicated by t...
Figure 2: Crystal structure of the product (rac)-15a.
Figure 3: Crystal structure of the product (rac)-15b.
Scheme 9: Reactions of the diester 16 with NBS or NIS in the presence or absence of Deoxo-Fluor®.
Scheme 10: Formation of the halolactons (rac)-17a,b. The initial attack of the halogen cation occurs at the st...
Scheme 11: Unsuccessful halofluorination of the bicyclic diester 18.
Scheme 12: Halofluorination reactions of the rigid tricyclic imine 19. The relevant NOESY interactions are mar...
Scheme 13: Mechanism of the halofluorination reactions of the substrate 19. X = Br (compounds a), I (compounds...
Scheme 14: Synthesis and halofluorination of the imide 24.
Scheme 15: Cyclizations of halofluorinated diesters with potassium tert-butoxide. Relevant NOESY interactions ...
Scheme 16: Mechanism of the reaction of the cyclopropanation of the compounds (rac)-2a,b and (rac)-5a with t-B...
Scheme 17: Presumed mechanism of the reaction of the compound (rac)-6b with t-BuOK.
Scheme 18: Cyclizations of halofluorinated tetrahydrophthalimides with DBU. Relevant NOESY interactions are ma...
Scheme 19: Mechanism for the formation of (rac)-28 from (rac)-11a,b. Although the formation of the compound (r...
Scheme 20: Fluoroselenations of the cyclohexenedicarboxylates (rac)-1 and 4.
Scheme 21: PhSe+-induced lactonization of the diester 16. Relevant NOESY interactions are marked with two-head...
Scheme 22: Oxidation of the fluoroselenide (rac)-30 under acidic and basic conditions.
Scheme 23: Oxidation of the fluoroselenide mixture (rac)-31 under acidic and basic conditions.
NMR Spectroscopy of supramolecular chemistry on protein surfaces
- Peter Bayer,
- Anja Matena and
- Christine Beuck
Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203
- Survivin – Histone H3 interaction by a GCP ligand has been shown to inhibit tumor proliferation in cell culture [46]. Porphyrins, either with or without a complexed metal ion in the center, have been used as planar hydrophobic scaffolds where either negatively charged carboxylate or positively charged
- they have been used to serve as scaffolds for the assembly of protein arrays and crystallization aids [23][24][25][26][27][28]. In addition, a terbiumIII complex termed crystallophore has been developed as a crystallographic nucleation and phasing tool for protein crystallography that can also easily
- multivalent ligands, like multi-armed GCP ligands with flexible scaffolds or nanoparticles, have been published yet. NMR spectroscopy is the ideal method to gain structural information and identify residues involved in ligand binding because it delivers single-residue resolution. It is also suitable to
Graphical Abstract
Figure 1: Ligands targeting charged areas on protein surfaces discussed in this review. The protein shown as ...
Figure 2: 1H NMR titration of lysine with tweezers. All signals show chemical shift perturbations and differe...
Figure 3: 1H,15N-HSQC Titration of full-length hPin1 with supramolecular tweezers (original data). (a) Spectr...
Figure 4: Relative signal intensities can be used to identify ligand binding sites (schematic representation ...
Figure 5: Schematic 1H,15N-HSQC spectrum of tauF4 (chemical shifts from BMRB # 17945, [109]) with and without spec...
Figure 6: H2(C)N spectra specific for arginine (a) and lysine (b) residues of the hPin1-WW domain at differen...
Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors
- Emine Kayahan,
- Mathias Jacobs,
- Leen Braeken,
- Leen C.J. Thomassen,
- Simon Kuhn,
- Tom van Gerven and
- M. Enis Leblebici
Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202
- an ene reaction of β-citronellol and Diels–Alder reactions of α-terpinene and (5-methylfuran-2-yl)methanol [46] as well as the synthesis of cyclopent-2-enones from furans [47] and the synthesis of diverse γ-lactam scaffolds [48]. Conversions larger than 90% were achieved for all reactions [46][47][48
Graphical Abstract
Figure 1: The momentum transport affects the mass transfer and the light field. All transport phenomena need ...
Figure 2: Common photomicroreactor designs: (a) Straight channel, (b) serpentine channel, (c) square serpenti...
Figure 3: Benchmarked photoreactors: (a) Microcapillaries in parallel, (b) microcapillaries in series, (c) fl...
Figure 4: Photochemical reactions that are detailed in Table 1.
Figure 5: Structured reactors designed for enhancing the mass transfer: (a) Packed bed photoreactor, (b) mono...
Figure 6: Comparison of the LED board designs of photomicroreactors: (a) CC array design, (b) MC array design...
Figure 7: Illustration of the light scattering phenomenon inside a photocatalytic flow reactor.
Figure 8: Efficiency of the absorption process in scattering situations with respect to pure absorption situa...
Figure 9: Different types of distributors: (a) Traditional or consecutive manifold, (b) bifurcation unit dist...
Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones
- Viktor M. Tkachuk,
- Oleh O. Lukianov,
- Mykhailo V. Vovk,
- Isabelle Gillaizeau and
- Volodymyr A. Sukach
Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191
- , heterocyclic analogues of activated ketimines (Figure 1), thus offering potential applications in the design of new heterocyclic chemotypes [21][22][23][24][25]. Compounds I are precursors of trifluoromethyl-substituted dihydropyrimidine derivatives which appear as original and potent scaffolds in medicinal
Graphical Abstract
Figure 1: Summary of the previous and present studies.
Scheme 1: Chan–Evans–Lam reaction of 4-trifluoromethylpyrimidin-2(1H)-one 1а with (het)aryl boronic acid 2b–w...
Scheme 2: Chan–Evans–Lam reaction of 4-trifluoromethylpyrimidin-2(1H)-one (1а) with (het)aryl- and alkenylbor...
Scheme 3: Chan–Evans–Lam reaction of pyrimidin-2(1H)-ones 1b–h with phenylboronic acid (2a).
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
- they are the most trustworthy strategies for direct functionalization of aromatic scaffolds [50]. As can be inspected from Scheme 18, monoiodosumanene 79 was obtained by gold-catalyzed iodination in the presence of N-iodosuccinimide (NIS). The mononitrosumanene 80 was achieved through the nitration
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.
Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups
- Benjamin Jeffries,
- Zhong Wang,
- Robert I. Troup,
- Anaïs Goupille,
- Jean-Yves Le Questel,
- Charlene Fallan,
- James S. Scott,
- Elisabetta Chiarparin,
- Jérôme Graton and
- Bruno Linclau
Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182
- (Figure 4), using the directly comparable isobutanol, cyclopropylmethanol and 3-oxetanylmethanol scaffolds. All compounds are either commercially available or are easily synthesized from available fluorinated building blocks. In addition, comparison of lipophilicities of relevant linear butanol
Graphical Abstract
Figure 1: Examples of lipophilicity modulation for geminal dimethyl to cyclopropyl and oxetane modifications ...
Figure 2: Lipophilicity modulation examples involving fluorinated cyclopropane derivatives (measured experime...
Figure 3: Lipophilicity changes upon fluorination of isopropyl, cyclopropane and oxetane rings (Series A, C: ...
Figure 4: Lipophilicity modulations discussed in this contribution.
Figure 5: Distribution of the experimental lipophilicity values of series D, E and F (* denotes an estimated ...
Figure 6: Comparison of lipophilicities between the linear alkyl, isopropyl, cyclopropyl, and 3-oxetanyl subs...
Figure 7: Comparison of lipophilicities between isopropyl and cyclopropyl substituents grouped by exchange of...
Figure 8: Carbon extensions.
Figure 9: Experimental and theoretical (in blue) values (calculated at the MN15/aug-cc-pVTZ//MN15/cc-pVTZ lev...
Figure 10: Correlation of the DFT-calculated lipophilicities with the experimental values. A) fluorinated seri...
Figure 11: Experimental (in black) and theoretical (in blue) values (calculated at the MN15/aug-cc-pVTZ//MN15/...
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
- ) using ethyl acetate/petroleum ether mixture to afford product 4. Examples of biologically active oxazole and aminothiazole scaffolds. Large-scale synthesis of 3i. a) At the start of the reaction, b) after the reaction. ORTEP diagram of compound 5. X-ray crystal structure of 4h. Strategies for the
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.
