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Search for "diazomethane" in Full Text gives 55 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
Graphical Abstract
Figure 1: Chemical structure of some natural ether lipids (ELs).
Figure 2: Synthesis of lyso-PAF and PAF from 1-O-alkylglycerol [64].
Figure 3: Synthesis of lyso-PAF from 1,3-benzylideneglycerol 3.1 [69].
Figure 4: A) Synthesis of the two enantiomers of octadecylglycerol (4.6 and 4.10) from ᴅ-mannitol (4.1); B) s...
Figure 5: Four-step synthesis of PAF 5.6 from (S)-glycidol [73].
Figure 6: Synthesis of 1-O-alkylglycerol A) from solketal, B) from ᴅ- or ʟ-tartaric acid and the intermediate ...
Figure 7: Synthesis of EL building blocks starting from substituted glycidol 7.1a–c [82].
Figure 8: Synthesis of PAF 8.5 by using phosphoramidite 8.2 [86].
Figure 9: Synthesis of oleyl-PAF 9.7 from ʟ-serine [88].
Figure 10: Synthesis of racemic analogues of lyso-PAF 10.8 and PAF 10.9 featuring a phenyl group between the g...
Figure 11: Synthesis of racemic deoxy-lyso-PAF 11.7 and deoxy-PAF 11.8 [91].
Figure 12: Synthesis of racemic thio-PAF 12.8 [93].
Figure 13: Racemic synthesis of 13.6 to illustrate the modification of the glycerol backbone by adding a methy...
Figure 14: Racemic synthesis of 14.5 as an illustration of the introduction of methyl substituents on the glyc...
Figure 15: Synthesis of functionalized sn-2-acyl chains of PC-EL; A) Steglich esterification or acylation reac...
Figure 16: Synthesis of racemic mc-PAF (16.3), a carbamate analogue of PAF [102].
Figure 17: A) Synthesis of (R)-17.2 and (S)-17.6 starting from (S)-solketal (17.1); B) synthesis of N3-PAF (17...
Figure 18: Modification of the phosphocholine polar head to produce PAF analogues [81].
Figure 19: Racemic PAF analogues 19.3 and 19.5 characterized by the absence of the phosphate group [107].
Figure 20: Synthesis of PIP3-PAF (20.7) [108].
Figure 21: Large-scale synthesis of C18-edelfosine (21.8) [116].
Figure 22: Synthesis of C16-edelfosine (22.10) starting from isopropylidene-ʟ-glyceric acid methyl ester (22.1...
Figure 23: Phosphocholine moiety installation by the use of chlorophosphite 23.2 as key reagent [119].
Figure 24: Synthesis of rac-1-alkyl-2-O-methylglycerol (AMG) [120].
Figure 25: Synthesis of stereocontrolled 1-alkyl-2-O-methyl glycerol 25.9 (AMG) from dimethyl ᴅ-tartrate [81].
Figure 26: A) Racemic synthesis of thioether 26.4 [129,130], B) structure of sulfone analogue 26.5 [129].
Figure 27: Stereocontrolled synthesis of C18-edelfosine thioether analogue 27.8 [118].
Figure 28: Synthesis of thioether 28.4 that include a thiophosphate function [134].
Figure 29: Synthesis of ammonium thioether 29.4 and 29.6 [135].
Figure 30: Synthesis of the N-methylamino analogue of edelfosine 30.6 (BN52211) [138].
Figure 31: Synthesis of 1-desoxy analogues of edelfosine; A) with a saturated alkyl chain; B) synthesis of the...
Figure 32: Stereocontrolled synthesis of edelfosine analogue (S)-32.8 featuring a C18:1 lipid chain [142].
Figure 33: Synthesis of edelfosine analogues with modulation of the lipid chain; A) illustration with the synt...
Figure 34: Synthesis of phospholipid featuring a carbamate function to link the lipid chain to the glycerol un...
Figure 35: Synthesis of sesquiterpene conjugates of phospho glycero ether lipids [148].
Figure 36: Racemic synthesis of methyl-substituted glycerol analogues 36.7 and 36.10: A) synthesis of diether ...
Figure 37: Racemic synthesis of ilmofosine (37.6) [155,156].
Figure 38: A) Stereoselective synthesis of 38.5 via a stereoselective hydroboration reaction; B) synthesis of ...
Figure 39: Racemic synthesis of SRI62-834 (39.6) featuring a spiro-tetrahydrofurane heterocycle in position 2 ...
Figure 40: Racemic synthesis of edelfosine analogue 40.5 featuring an imidazole moiety in sn-2 position [160].
Figure 41: Racemic synthesis of fluorine-functionalized EL: A) Synthesis of 41.6 and B) synthesis of 41.8 [161-163].
Figure 42: A) Synthesis of the β-keto-ester 42.6 that also features a decyl linker between the phosphate and t...
Figure 43: Synthesis of phosphonate-based ether lipids; A) edelfosine phosphonate analogue 43.7 and B) thioeth...
Figure 44: Enantioselective synthesis of phosphonates 44.3 and 44.4 [171].
Figure 45: Racemic synthesis of phosphinate-based ether lipid 45.10 [172].
Figure 46: Racemic synthesis of edelfosine arsonium analogue 46.5 [173].
Figure 47: Synthesis of edelfosine dimethylammonium analogue 47.2 [118].
Figure 48: Synthesis of rac-C18-edelfosine methylammonium analogue 48.4 [176].
Figure 49: A) Synthesis of edelfosine N-methylpyrrolidinium analogue 49.2 or N-methylmorpholinium analogue 49.3...
Figure 50: A) Synthesis of edelfosine’s analogue 50.4 with a PE polar group; B) illustration of a pyridinium d...
Figure 51: A) Synthesis of 51.4 featuring a thiazolium cationic moiety; B) synthesis of thiazolium-based EL 51...
Figure 52: Synthesis of cationic ether lipids 52.3, 52.4 and 52.6 [135,183].
Figure 53: Synthesis of cationic carbamate ether lipid 53.5 [184].
Figure 54: Synthesis of cationic sulfonamide 54.5 [185].
Figure 55: Chemical structure of ONO-6240 (55.1) and SRI-63-119 (55.2).
Figure 56: Synthesis of non-ionic ether lipids 56.2–56.9 [188].
Figure 57: Synthesis of ether lipid conjugated to foscarnet 57.6 [189].
Figure 58: A) Synthesis of ether lipid conjugated to arabinofuranosylcytosine; B) synthesis of AZT conjugated ...
Figure 59: Synthesis of quercetin conjugate to edelfosine [191].
Figure 60: Synthesis of 60.8 (Glc-PAF) [194].
Figure 61: A) Synthesis of amino ether lipid 61.7 functionalized with a rhamnose unit and its amide analogue 6...
Figure 62: A) Synthesis of glucose ether lipid 62.4; B) structure of ether lipid 62.5 possessing a maltose uni...
Figure 63: A) Synthesis of glucuronic methyl ester 63.8; B) structure of cellobiose 63.9 and maltose 63.10 ana...
Figure 64: A) Synthesis of maltosyl glycerolipid 64.7; B) structure of lactose analogue 64.8 prepared followin...
Figure 65: A) Asymmetric synthesis of the aglycone moiety starting from allyl 4-methoxyphenyl ether; B) glycos...
Figure 66: A) Synthesis of ohmline possessing a lactose moiety. B) Structure of other glyco glycero lipids pre...
Figure 67: A) Synthesis of lactose-glycerol ether lipid 67.5; B) analogues possessing a maltose (67.6) or meli...
Figure 68: Synthesis of digalactosyl EL 68.6, A) by using trityl, benzyl and acetyl protecting groups, B) by u...
Figure 69: A) Synthesis of α-ohmline; B) structure of disaccharide ether lipids prepared by using similar meth...
Figure 70: Synthesis of lactose ether lipid 70.3 and its analogue 70.6 featuring a carbamate function as linke...
Figure 71: Synthesis of rhamnopyranoside diether 71.4 [196].
Figure 72: Synthesis of 1-O-hexadecyl-2-O-methyl-3-S-(α-ᴅ-1'-thioglucopyranosyl)-sn-glycerol (72.5) [225].
Figure 73: A) Preparation of lipid intermediate 73.4; B) synthesis of 2-desoxy-C-glycoside 73.10 [226].
Figure 74: Synthesis of galactose-pyridinium salt 74.3 [228].
Figure 75: Synthesis of myo-inositol derivative Ino-C2-PAF (75.10) [230].
Figure 76: A) Synthesis of myo-inositol phosphate building block 76.7; B) synthesis of myo-inositolphosphate d...
Figure 77: A) Synthesis of phosphatidyl-3-desoxy-inositol 77.4; B) synthesis of phosphono-3-desoxyinositol 77.9...
Figure 78: A) Structure of diether phosphatidyl-myo-inositol-3,4-diphosphate 78.1; B) synthesis of phosphatidy...
Figure 79: A) Synthesis of diether-phosphatidyl derivative 79.4 featuring a hydroxymethyl group in place of a ...
Figure 80: Synthesis of Glc-amine-PAF [78].
Figure 81: Synthesis of glucosamine ether lipid 81.4 and its analogues functionalized in position 3 of the ami...
Figure 82: Synthesis of fully deprotected aminoglucoside ether lipid 82.5 [246].
Figure 83: Synthesis of C-aminoglycoside 83.12 using Ramberg–Bäcklund rearrangement as a key step [250].
Figure 84: A) List of the most important glyco lipids and amino glyco lipids included in the study of Arthur a...
Figure 85: Synthesis of mannosamine ether lipid 85.6 [254].
Figure 86: A) Synthesis of glucosamine ether lipids with a non-natural ʟ-glucosamine moiety; B) synthesis of e...
Figure 87: A) Structure of the most efficient anticancer agents 87.1–87.4 featuring a diamino glyco ether lipi...
Figure 88: A) Synthesis of diamino glyco ether lipid 87.4; B) synthesis of bis-glycosylated ether lipid 88.10 [256]....
Figure 89: Synthesis of triamino ether lipid 89.4 [260].
Figure 90: Synthesis of chlorambucil conjugate 90.7 [261].
Figure 91: Three main methods for the preparation of glycerol ether lipid 91.3; A) from solketal and via a tri...
Figure 92: Four different methods for the installation of the phosphocholine polar head group; A) method using...
Figure 93: Illustration of two methods for the installation of saccharides or aminosaccharides; A) O-glycosyla...
Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups
- Ita Hajdin,
- Romana Pajkert,
- Mira Keßler,
- Jianlin Han,
- Haibo Mei and
- Gerd-Volker Röschenthaler
Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39
- ). In addition, few examples of difluoromethylphosphonate containing cyclopropanes have been reported to date. These compounds were synthesized either by cyclopropanation of CF2P(O)(OEt)2-containing alkenoates using a Corey–Chaykovsky reagent (sulfaniumyl or oxosulfaniumyl methanides) and diazomethane
Graphical Abstract
Scheme 1: Previous works (A–D) and the extension (this work).
Scheme 2: Synthesis of diethyl 2-diazo-1,1,3,3,3-pentafluoropropylphosphonate (5).
Scheme 3: Scope of the cyclopropanation. Reaction conditions: alkene (0.15 mmol), diazo compound 5 (0.1 mmol)...
Figure 1: 19F,1H-HOESY spectrum of compound 6c.
Scheme 4: Scope of the cyclopropanation. Reaction conditions: alkene (0.15 mmol), diazo compound 5 (0.1 mmol)...
Scheme 5: Addition of CuI to the diazo compound 5.
Scheme 6: Possible addition of styrene to Int2 yielding Int4_1 and Int4_2 through Int3_1 and Int3_2.
Scheme 7: Possible addition of styrene to Int2 yielding Int4_3 and Int4_4 without further intermediates.
Scheme 8: Formation of the products Pr1 to Pr4.
Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C
- Karolina Wątroba,
- Małgorzata Pawełczak and
- Marcin Kaźmierczak
Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33
- ]. Other inhibitors are dipeptide derivatives showing substrate-like sequences. One of the most effective inhibitors is the dipeptide Gly-Phe-CHN2 (glycylphenylalanine-diazomethane), which, however, has not been used as a therapeutic substance due to the instability of the diazomethylketone group [8][9
Graphical Abstract
Scheme 1: Synthetic strategy towards 5 and 7.
Scheme 2: Synthesis of 9 and 11. (a) R = -CH3; (b) R = -CH(CH3)2; (c) R = -CH2CH(CH3)2; (d) R = -CH(CH3)CH2CH3...
Figure 1: Dixon plot for the hydrolysis of Gly-Phe-pNA substrate catalyzed by bovine cathepsin C in the prese...
Modern flow chemistry – prospect and advantage
- Philipp Heretsch
Beilstein J. Org. Chem. 2023, 19, 33–35, doi:10.3762/bjoc.19.3
- mesylate, diazomethane was an inevitable necessity. By moving the generation of this toxic and explosive reagent into a continuous process with manageable amounts present at any given point and continuously stripping the chemical with a stream of nitrogen, safety protocols could be met [10]. Among the
A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction
- Ksenia Malkova,
- Andrey Bubyrev,
- Vasilisa Krivovicheva,
- Dmitry Dar’in,
- Alexander Bunev and
- Mikhail Krasavin
Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175
- proceeded further, in uncatalyzed fashion at room temperature and yielded, after intramolecular azide–alkyne click reaction novel, structurally intriguing bistriazoles. Keywords: α-acetyl-α-diazomethane sulfonamide; intramolecular click reaction; uncatalyzed; room temperature; 1,2,3-triazoles
Graphical Abstract
Figure 1: (a) Previously developed three-component approach to 1,5-disubstituted 1,2,3-triazoles; (b) double ...
Scheme 1: Results of a trial reaction between 1, o-azidobenzaldehyde (3a) and propargylamine.
Figure 2: Diversely bioactive compounds based on scaffolds A and B.
Scheme 2: Three-component reaction of 1, propargylamine and various o-azidobenzaldehydes.
Figure 3: Aromatic azido aldehydes 3j–l that failed to react with 1 and propargylamine.
Scheme 3: Variations of the amine component in the reactions with 1 and 3a.
A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles
- Pavel A. Topanov,
- Anna A. Maslivets,
- Maksim V. Dmitriev,
- Irina V. Mashevskaya,
- Yurii V. Shklyaev and
- Andrey N. Maslivets
Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162
- compounds to molecules containing an enone fragment. Cycloaddition reactions involving diazo and enone moieties are usually carried out using transition-metal catalysis [18][19][20], with catalyst-free reactions being carried out only with the participation of reactive unsubstituted diazomethane [21][22][23
Graphical Abstract
Figure 1: Selected examples of biologically active natural products bearing a spirofuranoxindole moiety.
Scheme 1: Synthesis of spiro[dihydrofuran-2,3'-oxindoles] from enones and diazooxindoles.
Scheme 2: Cycloaddition reactions of [e]-fused 1H-pyrrole-2,3-diones.
Scheme 3: The model reaction of FPD 1a and diazooxindole 2a.
Scheme 4: The reaction of FPD 1k with diazooxindole 2a.
Scheme 5: A) Plausible mechanism of formal [4 + 1] cycloaddition of FPDs 1 with diazooxindoles 2 (negative ch...
A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH4/I2 system
- Lin Chen,
- Xuan Zhou,
- Zhiyong Chen,
- Changxu Wang,
- Shunjie Wang and
- Hanbing Teng
Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104
- chemicals, agrochemicals, pharmaceuticals and dyes [1][2][3][4]. Traditional methods for the preparation of N-methylamines involve the direct methylation of amines by using methyl halides [5][6][7], dimethyl sulfate [8], diazomethane [9], methyl triflate [10][11] or dimethyl carbonate [12][13][14][15] as
Graphical Abstract
Scheme 1: The synthesis of formamides and monomethylamines.
Scheme 2: The possible reaction mechanism. RDS = rate determining step.
An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates
- Timur O. Zanakhov,
- Ekaterina E. Galenko,
- Mikhail S. Novikov and
- Alexander F. Khlebnikov
Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74
- cyanation of the resulted isoxazoles 8a–f to cyanides 9a–f using Me2C(OH)CN/(Me2N)2C=NH [29], their acid hydrolysis, followed by esterification of the resulting acids 9a–f with diazomethane. 4-Iodoisoxazoles 12a–f, necessary for the preparation of 3,4-disubstituted isoxazoles, were obtained by iodination of
Graphical Abstract
Scheme 1: Approaches to the synthesis of alkyl 4-oxo-1,4-dihydropyridine-3-carboxylates.
Scheme 2: Synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates.
Scheme 3: Synthesis of Isoxazoles 11–13.
Scheme 4: Synthesis of isoxazoles 1.
Scheme 5: Synthesis of pyridones 2.
Scheme 6: Transformations of pyridones 2.
Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction
- Irina Kuznetcova,
- Felix Bacher,
- Daniel Vegh,
- Hsiang-Yu Chuang and
- Vladimir B. Arion
Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15
- was observed by TLC. However, the acid chloride reacted very sluggishly with (CH3)3SiCHN2, which is a safe alternative to the highly explosive diazomethane [34]. Another attempt to synthesize the open-chain precursor from indole and 2-bromo-N-(2-bromophenyl)acetamide by regioselective palladium
Graphical Abstract
Figure 1: Paullone related indolobenzazepinone isomers. 7,12-Dihydroindolo[3,2-d][1]benzazepin-6(5H)-one or p...
Scheme 1: Investigated retrosynthetic pathways to scaffold C.
Scheme 2: Attempted synthesis of scaffold C by route (a).
Scheme 3: Attempted synthesis of C by route (b).
Scheme 4: Attempted synthesis of N-benzylated indole-2-acetic acid.
Scheme 5: Attempt to obtain open-chain precursor N-(2-bromophenyl)-2-(1H-indol-2-yl)acetamide.
Scheme 6: Synthesis of scaffold C and analogues by route (c).
Figure 2: ORTEP view of 1a with thermal ellipsoids drawn at the 50% probability level.
Figure 3: ORTEP view of 3a with thermal ellipsoids drawn at the 50% probability level.
Scheme 7: Attempted Ullmann cross-coupling of 23 with o-bromo-nitrobenzene.
Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes
- Shun Saito,
- Kanji Indo,
- Naoya Oku,
- Hisayuki Komaki,
- Masashi Kawasaki and
- Yasuhiro Igarashi
Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203
- -diazomethane and the resulting methyl ester 4' was acylated with (R)- or (S)-α-methoxyphenylacetic acid (MPA). To our surprise, however, 1H NMR spectra of both the acylation products were substantially the same but contained several duplicated signals with contrasting peak intensities, indicating 4 to be an
- CHCl3/MeOH (25 μL each) was added a solution of TMS-diazomethane in n-hexane (2.0 M, 25 μL) at room temperature. After stirring for 15 min, the reaction mixture was concentrated to dryness to give methyl ester 4' (0.2 mg). Methyl ester 4': 1H NMR (500 MHz, CDCl3) δ 3.76 (s, 3H, -CO2CH3), 7.14 (brs 1H
Graphical Abstract
Figure 1: Structures of 1–6.
Figure 2: COSY, key HMBC and NOESY correlations of 1–5.
Figure 3: 1H NMR spectra and partial chemical shift assignments for MPA esters 4'a–4'd. Upper: (R)-MPA acylat...
Figure 4: Chiral phase HPLC analysis of methyl ester 4'. Italicized numbers indicate peak areas.
Figure 5: COSY and key HMBC correlations observed for 6.
Figure 6: ΔδH(S-R) values in ppm calculated from PGME amides 6a and 6b.
Figure 7: Selected examples of the related compounds derived from the strains in the genus Streptomyces (a) a...
Synthesis of O6-alkylated preQ1 derivatives
- Laurin Flemmich,
- Sarah Moreno and
- Ronald Micura
Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147
- potential O6-methylated precursor of m6preQ1, namely N9-trimethysilylethyl protected m6preQ0 [20]. This synthesis, however, is based on methylation using diazomethane resulting in a mixture of N1 and O6 methylated products, and we therefore did not further consider this path. Finally, one route was
Graphical Abstract
Scheme 1: Chemical structures of queuine (Q base) and the hypermodified nucleoside queuosine (Q), the natural...
Scheme 2: Synthesis of compound 1 (m6preQ0) by cyclocondensation using a 4-methoxypyrimidine derivative resul...
Scheme 3: Synthesis of compound 3 following known procedures [31-33].
Scheme 4: The five-step synthesis of m6preQ1 2 from compound 3 required derivatization to make the intermedia...
Scheme 5: The synthesis of e6preQ1 (2a) and bn6preQ1 (2b) was performed in analogy to the route outlined in Scheme 4 ...
Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications
- Christopher Liczner,
- Kieran Duke,
- Gabrielle Juneau,
- Martin Egli and
- Christopher J. Wilds
Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76
- by 5'-tritylation. In the case of guanosine, this strategy for 2'-OH methylation was unsuccessful, owing again to undesired methylation at the nucleobase. Instead, the 5'-O-monomethoxytrityl derivative of N2-isobutyrylguanosine was treated with diazomethane in dimethylformamide in the presence of tin
Graphical Abstract
Figure 1: Structures of the chemically modified oligonucleotides (A) N3' → P5' phosphoramidate linkage, (B) a...
Scheme 1: Synthesis of a N3' → P5' phosphoramidate linkage by solid-phase synthesis. (a) dichloroacetic acid;...
Figure 2: Crystal structures of (A) N3' → P5' phosphoramidate DNA (PDB ID 363D) [71] and (B) amide (AM1) RNA in c...
Scheme 2: Synthesis of a phosphorodithioate linkage by solid-phase synthesis. (a) detritylation; (b) tetrazol...
Figure 3: Close-up view of a key interaction between the PS2-modified antithrombin RNA aptamer and thrombin i...
Scheme 3: Synthesis of the (S)-GNA thymine phosphoramidite from (S)-glycidyl 4,4'-dimethoxytrityl ether. (a) ...
Figure 4: Surface models of the crystal structures of RNA dodecamers with single (A) (S)-GNA-T (PDB ID 5V1L) [54]...
Figure 5: Structures of 2'-O-alkyl modifications. (A) 2'-O-methoxy RNA (2'-OMe RNA), (B) 2'-O-(2-methoxyethyl...
Scheme 4: Synthesis of the 2'-OMe uridine from 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)uridine. (a) Benzoy...
Scheme 5: Synthesis of the 2'-O-MOE uridine from uridine. (a) (PhO)2CO, NaHCO3, DMA, 100 °C; (b) Al(OCH2CH2OCH...
Figure 6: Structure of 2'-O-(2-methoxyethyl)-RNA (MOE-RNA). (A) View into the minor groove of an A-form DNA d...
Figure 7: Structures of locked nucleic acids (LNA)/bridged nucleic acids (BNA) modifications. (A) LNA/BNA, (B...
Scheme 6: Synthesis of the uridine LNA phosphoramidite. (a) i) NaH, BnBr, DMF, ii) acetic anhydride, pyridine...
Scheme 7: Synthesis of the 2'-fluoroarabinothymidine. (a) 30% HBr in acetic acid; (b) 2,4-bis-O-(trimethylsil...
Figure 8: Sugar puckers of arabinose (ANA) and arabinofluoro (FANA) nucleic acids compared with the puckers o...
Figure 9: Structures of C4'-modified nucleic acids. (A) 4'-methoxy, (B) 4'-(2-methoxyethoxy), (C) 2',4'-diflu...
Scheme 8: Synthesis of the 4'-F-rU phosphoramidite. (a) AgF, I2, dichloromethane, tetrahydrofuran; (b) NH3, m...
Scheme 9: Synthesis of the thymine FHNA phosphoramidite. (a) thymine, 1,8-diazabicyclo[5.4.0]undec-7-ene, ace...
Scheme 10: Synthesis of the thymine Ara-FHNA phosphoramidite. (a) i) trifluoromethanesulfonic anhydride, pyrid...
Figure 10: Crystal structures of (A) FHNA and (B) Ara-FHNA in modified A-form DNA decamers (PDB IDs 3Q61 and 3...
[2 + 1] Cycloaddition reactions of fullerene C60 based on diazo compounds
- Yuliya N. Biglova
Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55
- ethereal solution of diazomethane in toluene at 0 °C resulted in pyrazoline derivative C [81]. The adduct isolated chromatographically was exposed to ultraviolet (UV) irradiation for 25 min at 25 °C in a quartz tube. The resulting isomers 3 and 4 were separated by reversed-phase high-performance liquid
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
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,...
A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions
- Munmun Ghosh,
- Valmik S. Shinde and
- Magnus Rueping
Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264
- sequential reports, Feroci and Inesi discussed the electrochemical carboxylation of chiral α-bromocarboxylic acid derivatives 165 substituted with Evans-type chiral auxiliaries [96][97]. The cathodic reduction of the C–Br bond in presence of CO2 followed by treatment with diazomethane resulted in the
- transformations, Feroci and Inesi developed a stereoselective carboxylation of cinnamic acid derivatives 171 substituted with chiral auxiliaries [99]. The substrate 171 was subjected to galvanostatic reduction under CO2 atmosphere in an undivided cell. Carboxylation followed by treatment with diazomethane
Graphical Abstract
Figure 1: General classification of asymmetric electroorganic reactions.
Scheme 1: Asymmetric reduction of 4-acetylpyridine using a modified graphite cathode.
Scheme 2: Asymmetric hydrogenation of ketones using Raney nickel powder electrodes modified with optically ac...
Scheme 3: Asymmetric reduction of prochiral activated olefins with a poly-ʟ-valine-coated graphite cathode.
Scheme 4: Asymmetric reduction of prochiral carbonyl compounds, oximes and gem-dibromides on a poly-ʟ-valine-...
Scheme 5: Asymmetric hydrogenation of prochiral ketones with poly[RuIII(L)2Cl2]+-modified carbon felt cathode...
Scheme 6: Asymmetric hydrogenation of α-keto esters using chiral polypyrrole film-coated cathode incorporated...
Scheme 7: Quinidine and cinchonidine alkaloid-induced asymmetric electroreduction of acetophenone.
Scheme 8: Asymmetric electroreduction of 4- and 2-acetylpyridines at a mercury cathode in the presence of a c...
Scheme 9: Enantioselective reduction of 4-methylcoumarin in the presence of catalytic yohimbine.
Scheme 10: Cinchonine-induced asymmetric electrocarboxylation of 4-methylpropiophenone.
Scheme 11: Enantioselective hydrogenation of methyl benzoylformate using an alkaloid entrapped silver cathode.
Scheme 12: Alkaloid-induced enantioselective hydrogenation using a Cu nanoparticle cathode.
Scheme 13: Alkaloid-induced enantioselective hydrogenation of aromatic ketones using a bimetallic Pt@Cu cathod...
Scheme 14: Enantioselective reduction of ketones at mercury cathode using N,N'-dimethylquininium tetrafluorobo...
Scheme 15: Asymmetric synthesis of an amino acid using an electrode modified with amino acid oxidase and elect...
Scheme 16: Asymmetric oxidation of p-tolyl methyl sulfide using chemically modified graphite anode.
Scheme 17: Asymmetric oxidation of unsymmetric sulfides using poly(amino acid)-coated electrodes.
Scheme 18: Enantioselective, electocatalytic oxidative coupling on TEMPO-modified graphite felt electrode in t...
Scheme 19: Asymmetric electrocatalytic oxidation of racemic alcohols on a TEMPO-modified graphite felt electro...
Scheme 20: Asymmetric electrocatalytic lactonization of diols on TEMPO-modified graphite felt electrodes.
Scheme 21: Asymmetric electrochemical pinacolization in a chiral solvent.
Scheme 22: Asymmetric electroreduction using a chiral supporting electrolyte.
Scheme 23: Asymmetric anodic oxidation of enol acetates using chiral supporting electrolytes.
Scheme 24: Kinetic resolution of primary amines using a chiral N-oxyl radical mediator.
Scheme 25: Chiral N-oxyl-radical-mediated kinetic resolution of secondary alcohols via electrochemical oxidati...
Scheme 26: Chiral iodoarene-mediated asymmetric electrochemical lactonization.
Scheme 27: Os-catalyzed electrochemical asymmetric dihydroxylation of olefins using the Sharpless ligand and i...
Scheme 28: Asymmetric electrochemical epoxidation of olefins catalyzed by a chiral Mn-salen complex.
Scheme 29: Asymmetric electrooxidation of 1,2-diols, and amino alcohols using a chiral copper catalyst.
Scheme 30: Mechanism of asymmetric electrooxidation of 1,2-diols, and amino alcohols using a chiral copper cat...
Scheme 31: Enantioselective electrocarboxylation catalyzed by an electrogenerated chiral [CoI(salen)]− complex....
Scheme 32: Asymmetric oxidative cross coupling of 2-acylimidazoles with silyl enol ethers.
Scheme 33: Ni-catalyzed asymmetric electroreductive cleavage of allylic β-keto ester 89.
Scheme 34: Asymmetric alkylation using a combination of electrosynthesis and a chiral Ni catalyst.
Scheme 35: Mechanism of asymmetric alkylation using a combination of electrosynthesis and a chiral Ni catalyst....
Scheme 36: Asymmetric epoxidation by electrogenerated percarbonate and persulfate ions in the presence of chir...
Scheme 37: α-Oxyamination of aldehydes via anodic oxidation catalyzed by chiral secondary amines.
Scheme 38: The α-alkylation of aldehydes via anodic oxidation catalyzed by chiral secondary amines.
Scheme 39: Mechanism of α-alkylation of aldehydes via anodic oxidation catalyzed by chiral secondary amines.
Scheme 40: Electrochemical chiral secondary amine-catalyzed intermolecular α-arylation of aldehydes.
Scheme 41: Mechanism of electrochemical chiral secondary amine-catalyzed intermolecular α-arylation of aldehyd...
Scheme 42: Asymmetric cross-dehydrogenative coupling of tertiary amines with simple ketones via an electrochem...
Scheme 43: Electroenzymatic asymmetric reduction using enoate reductase.
Scheme 44: Assymetric reduction using alcohol dehydrogenase as the electrocatalyst.
Scheme 45: Asymmetric electroreduction catalyzed by thermophilic NAD-dependent alcohol dehydrogenase.
Scheme 46: Asymmetric epoxidation of styrene by electrochemical regeneration of flavin-dependent monooxygenase....
Scheme 47: Asymmetric electroreduction using a chloroperoxidase catalyst.
Scheme 48: Asymmetric electrochemical transformation mediated by hydrophobic vitamin B12.
Scheme 49: Diastereoselective cathodic reduction of phenylglyoxalic acids substituted with amines as chiral au...
Scheme 50: Ni-catalyzed asymmetric electroreductive cross coupling of aryl halides with α-chloropropanoic acid...
Scheme 51: Electrochemical Mannich addition of silyloxyfuran to in situ-generated N-acyliminium ions.
Scheme 52: Stereoselective electroreductive homodimerization of cinnamates attached to a camphor-derived chira...
Scheme 53: Diastereoselective electrochemical carboxylation of chiral α-bromocarboxylic acid derivatives.
Scheme 54: Electrocatalytic stereoselective conjugate addition of chiral β-dicarbonyl compounds to methyl viny...
Scheme 55: Stereoselective electrochemical carboxylation of chiral cinnamic acid derivatives under a CO2 atmos...
Scheme 56: Electrochemical diastereoselective α-alkylation of pyrrolidines attached with phosphorus-derived ch...
Scheme 57: Electrogenerated cyanomethyl anion-induced synthesis of chiral cis-β-lactams from amides bearing ch...
Scheme 58: Diastereoselective anodic oxidation followed by intramolecular cyclization of ω-hydroxyl amides bea...
Scheme 59: Electrochemical deprotonation of Ni(II) glycinate containing (S)-BPB as a chiral auxiliary: diaster...
Scheme 60: Enantioselective electroreductive coupling of diaryl ketones with α,β-unsaturated carbonyl compound...
Scheme 61: Asymmetric total synthesis of ropivacaine and its analogues using a electroorganic reaction as a ke...
Scheme 62: Asymmetric total synthesis of (−)-crispine A and its natural enantiomer via anodic cyanation of tet...
Scheme 63: Asymmetric oxidative electrodimerization of cinnamic acid derivatives as key step for the synthesis...
Enantioselective PCCP Brønsted acid-catalyzed aza-Piancatelli rearrangement
- Gabrielle R. Hammersley,
- Meghan F. Nichol,
- Helena C. Steffens,
- Jose M. Delgado,
- Gesine K. Veits and
- Javier Read de Alaniz
Beilstein J. Org. Chem. 2019, 15, 1569–1574, doi:10.3762/bjoc.15.160
- hydrogen bond group afforded the best selectivity (7k). To simplify the purification process, all acid products were transformed into the corresponding methyl ester in situ using (trimethylsilyl)diazomethane. A slight drop in enantioselectivity is observed when the benzoic acid group was moved to the meta
- -Piancatelli reaction. Asymmetric aza-Piancatelli rearrangement with a range of substituted anilines. *To simplify the purification process, carboxylic acids were transformed in situ into the corresponding methyl ester using (trimethylsilyl)diazomethane. Asymmetric aza-Piancatelli rearrangement with a range of
- substituted furylcarbinols. *To simplify the purification process, carboxylic acids were transformed in situ into the corresponding methyl ester using (trimethylsilyl)diazomethane. Initial optimization studies. Supporting Information Supporting Information File 226: Experimental part and copies of NMR
Graphical Abstract
Figure 1: Proposed mechanism of the asymmetric aza-Piancatelli reaction.
Scheme 1: Asymmetric aza-Piancatelli rearrangement with a range of substituted anilines. *To simplify the pur...
Scheme 2: Asymmetric aza-Piancatelli rearrangement with a range of substituted furylcarbinols. *To simplify t...
Synthesis of nonracemic hydroxyglutamic acids
- Dorota G. Piotrowska,
- Iwona E. Głowacka,
- Andrzej E. Wróblewski and
- Liwia Lubowiecka
Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22
- . Intermediary diacid was first esterified with diazomethane, then the isopropylidene acetal was hydrolyzed, and diester saponification gave N-Boc-protected compound (2S,3R)-35. Via ketopinic acid functionalized 2(3H)-oxazolones When oxazolone 36 derived from (R)-(−)-ketopinic acid was reacted with bromine and
- . Ozone efficiently completed the degradation of the furan ring to the carboxyl group which was esterified with diazomethane to give methyl (2S,3S)-3-acetoxypyroglutamate (2S,3S)-54, a cyclized variant of 3-hydroxyglutamic acid. Treatment with a concentrated acid afforded (2S,3S)-2 as the hydrochloride
Graphical Abstract
Figure 1: Structure of L-glutamic acid.
Figure 2: 3-Hydroxy- (2), 4-hydroxy- (3) and 3,4-dihydroxyglutamic acids (4).
Figure 3: Enantiomers of 3-hydroxyglutamic acid (2).
Scheme 1: Synthesis of (2S,3R)-2 from (R)-Garner's aldehyde. Reagents and conditions: a) MeOCH=CH–CH(OTMS)=CH2...
Scheme 2: Synthesis of (2S,3R)-2 and (2S,3S)-2 from (R)-Garner’s aldehyde. Reagents and conditions: a) H2C=CH...
Scheme 3: Two-carbon homologation of the protected L-serine. Reagents and conditions: a) Fmoc-succinimide, Na2...
Scheme 4: Synthesis of di-tert-butyl ester of (2R,3S)-2 from L-serine. Reagents and conditions: a) PhSO2Cl, K2...
Scheme 5: Synthesis of (2R,3S)-2 from O-benzyl-L-serine. Reagents and conditions: a) (CF3CH2O)2P(O)CH2COOMe, ...
Scheme 6: Synthesis of (2S,3R)-2 employing a one-pot cis-olefination–conjugate addition sequence. Reagents an...
Scheme 7: Synthesis of the orthogonally protected (2S,3R)-2 from a chiral aziridine. Reagents and conditions:...
Scheme 8: Synthesis of N-Boc-protected (2S,3R)-2 from D-phenylglycine. Reagents and conditions: a) BnMgCl, et...
Scheme 9: Synthesis of (2S,3R)-2 employing ketopinic acid as chiral auxiliary. Reagents and conditions: a) Br2...
Scheme 10: Synthesis of dimethyl ester of (2S,3R)-2 employing (1S)-2-exo-methoxyethoxyapocamphane-1-carboxylic...
Scheme 11: Synthesis of N-Boc-protected dimethyl ester of (2S,3R)-2 from (S)-N-(1-phenylethyl)thioacetamide. R...
Scheme 12: Synthesis of N-Boc-protected dimethyl ester of (2S,3R)-2 via Sharpless epoxidation. Reagents and co...
Scheme 13: Synthesis of (2S,3S)-2 from the imide 51. Reagents and conditions: a) NaBH4, MeOH/CH2Cl2; b) Ac2O, ...
Scheme 14: Synthesis of (2R,3S)-2 and (2S,3S)-2 from the acetolactam 55 (PMB = p-methoxybenzyl). Reagents and ...
Scheme 15: Synthesis of (2S,3R)-2 from D-glucose. Reagents and conditions: a) NaClO2, 30% H2O2, NaH2PO4, MeCN;...
Figure 4: Enantiomers of 3-hydroxyglutamic acid (3).
Scheme 16: Synthesis of (4S)-4-hydroxy-L-glutamic acid [(2S,4S)-3] by electrophilic hydroxylation. Reagents an...
Scheme 17: Synthesis of all stereoisomers of 4-hydroxyglutamic acid (3). Reagents and conditions: a) Br2, PBr5...
Scheme 18: Synthesis of the orthogonally protected 4-hydroxyglutamic acid (2S,4S)-73. Reagents and conditions:...
Scheme 19: Synthesis of (2S,4R)-4-acetyloxyglutamic acid as a component of a dipeptide. Reagents and condition...
Scheme 20: Synthesis of N-Boc-protected dimethyl esters of (2S,4R)- and (2S,4S)-3 from (2S,4R)-4-hydroxyprolin...
Scheme 21: Synthesis of orthogonally protected (2S,4S)-3 from (2S,4R)-4-hydroxyproline. Reagents and condition...
Scheme 22: Synthesis of the protected (4R)-4-hydroxy-L-pyroglutamic acid (2S,4R)-87 by electrophilic hydroxyla...
Figure 5: Enantiomers of 3,4-dihydroxy-L-glutamic acid (4).
Scheme 23: Synthesis of (2S,3S,4R)-4 from the epoxypyrrolidinone 88. Reagents and conditions: a) MeOH, THF, KC...
Scheme 24: Synthesis of (2S,3R,4R)-4 from the orthoester 92. Reagents and conditions: a) OsO4, NMO, acetone/wa...
Scheme 25: Synthesis of (2S,3S,4S)-4 from the aziridinolactone 95. Reagents and conditions: a) BnOH, BF3·OEt2,...
Scheme 26: Synthesis of (2S,3S,4R)-4 and (2R,3S,4R)-4 from cyclic imides 106. Reagents and conditions: a) NaBH4...
Scheme 27: Synthesis of (2R,3R,4R)-4 and (2S,3R,4R)-4 from the cyclic meso-imide 110. Reagents and conditions:...
Scheme 28: Synthesis of (2S,3S,4S)-4 from the protected serinal (R)-23. Reagents and conditions: a) Ph3P=CHCOO...
Scheme 29: Synthesis of (2S,3S,4S)-4 from O-benzyl-N-Boc-D-serine. Reagents and conditions: a) ClCOOiBu, TEA, ...
Scheme 30: Synthesis of (2S,3S,4R)-127 by enantioselective conjugate addition and asymmetric dihydroxylation. ...
Figure 6: Structures of selected compounds containing hydroxyglutamic motives (in blue).
Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS
- Sven Thierbach,
- Max Wienhold,
- Susanne Fetzner and
- Ulrich Hennecke
Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18
- dimethyl sulfate mainly N-methylation was observed accompanied by a small amount of the N,O-dimethylquinolonium ion. Pure NMe-HHQ (2) was obtained in moderate yield of 51% by column chromatography (Scheme 1). Selective O-methylation of an AQ has been reported using diazomethane [1]. To avoid explosive
- diazomethane, methylation of HHQ with trimethylsilyldiazomethane (TMS-DA) in methanol was carried out, which indeed provided selectively OMe-HHQ (3). However, even using a large excess of TMS-DA low conversion and yields of less than 20% OMe-HHQ (3) were observed. Addition of HBF4 did improve the reactivity
Graphical Abstract
Scheme 1: Methylation of HHQ (1).
Scheme 2: Synthesis of methylated HQNO derivatives.
Scheme 3: Synthesis of methylated PQS derivatives.
Figure 1: Overview of AQ compounds (A), and effect of AQs on the growth of S. aureus Newman (B). 24-Well plat...
Figure 2: Inhibition of cellular O2 consumption rate (cOCR) of S. aureus Newman. Cell suspensions (OD600 nm o...
Figure 3: Impact on AQ quorum sensing by the newly synthesized AQ derivatives. Cultures of P. aeruginosa PAO1...
Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis
- Robby Vroemans,
- Yenthel Verhaegen,
- My Tran Thi Dieu and
- Wim Dehaen
Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246
- ], via intramolecular cyclization of a diazomethane group and a nitrile [23], or via our recently reported NH-triazole synthesis starting from 6-methoxyflavanone [24]. Furthermore, 1,4,5-trisubstituted 1,2,3-triazole annulated chromenes have been reported via an intramolecular arylation reaction of 1,2,3
Graphical Abstract
Scheme 1: Two-step reaction towards triazolochromene 5a and obtained oxidized side product 6.
Scheme 2: Reaction pathways leading to the different regioisomers.
Figure 1: Scope with respect to various salicylaldehydes 1a–f, nitroalkenes 2a–d and organic azides 4a–g. aRe...
Scheme 3: Synthesis of bis-chromenotriazole 5p.
Figure 2: Generality of products obtained via the two-pot mechanochemical procedure, varying the salicylaldeh...
Scheme 4: Scale-up of the one-pot three-component reaction and two-step ball milling procedure.
Scheme 5: Postfunctional transformations of triazolochromenes.
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
- tropone unit: In 1975, Franck-Neumann and Martina reported the reaction of dimethyl diazomethane with tropone and benzotropones [83]. This reaction gave benzo-4,5-dimethyl-8,8-cyclooctatrienone (94, 30% isolable yield) as an insertion product via a carbonyl group and pyrazoline 95 as 1,3-dipolar addition
- unit: The ring-expansion product 188, which is a net insertion of a diazomethane unit into the tropone, was prepared from the reaction of 2,3-benzotropone (12) with dimethyl diazomethane (Figure 7) [83]. Benzohomoazocines 191–193 and benzomethoxyazocines 195–197 were prepared using a similar protocol
- depicted in Scheme 38 (Scheme 45) [161]. Sato’s group reported the synthesis of 7-hydroxy-2,3-benzotropone (241) via the ring expansion pathway of β-naphthoquinone (280) with diazomethane under various conditions and hydrolysis steps (Scheme 46) [169]. The boron trifluoride etherate-promoted ring expansion
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.
Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models
- Vladimir Kubyshkin and
- Nediljko Budisa
Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241
- fluorination of peptide scaffolds. One of these methods involves esterification of the C-terminus of peptides using a diazomethane species. Here, we provide an investigation of the physicochemical consequences of peptide esterification with partially fluorinated ethyl groups. Derivatives of N-acetylproline are
- . Although the yield increased, it remained low (20%). The poor yields in the aqueous medium are explained by the high reactivity of the diazomethane species, which favors nonspecific reactions in water [52]. Very recently, more specific diazomethane reagents for water-tolerant esterification have also been
- polyproline-II stability. This effect contrasts with the effects of other terminal modifications, such as aromatic amino acids, which reduce the polyproline-II fold stability [86]. We then prepared hexaproline peptide 8a, which was subsequently esterified with the diazomethane reagent to give 8b. Methyl ester
Graphical Abstract
Figure 1: A. Dependence of the lipophilicity (logP) on the number of fluorine atoms in a partially fluorinate...
Scheme 1: Synthesis of the model compounds.
Figure 2: Kinetics of the C-terminal ester hydrolysis.
Figure 3: Partitioning of the esters 1–5 between octan-1-ol and water. Insert: comparison with the other part...
Scheme 2: Amide isomerism in the N-acetylprolyl fragment.
Figure 4: Enhancement of the trans/cis thermodynamic preferences in the ester models as a function of the sol...
Scheme 3: A. Four-state conformational equilibrium model used by Siebler et al. [72] for explanations of the elev...
Scheme 4: Elevation of the trans/cis ratio in derivatives of N-acyl proline may result from the enhanced n→π*...
Scheme 5: Synthesis of the model peptides.
Figure 5: Mean residue molar circular dichroism (Δε) of peptides 8–10 in methanol (left) and aqueous phosphat...
Figure 6: Conformational analysis of the peptides by 1H DOSY NMR (D2O, 298 K). The theoretical values were ca...
Figure 7: Hydrolysis of the C-terminal 2,2-difluoroethyl esters of the oligopeptides in buffered deuterium ox...
Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies
- Grzegorz Mlostoń and
- Heinz Heimgartner
Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221
- reactions with diazomethane albeit in very low yields [29]. [2 + 2]-Cycloadditions The electron-deficient dicyanofumarates E-1 react with electron-rich ethenes, yielding cyclobutane derivatives as product of [2 + 2]-cycloadditions. Depending on the reaction conditions and on the type of the electron-rich
- cyclopropane derivatives. The treatment of methyl 3-methyl-2-oxodithiobutanoate with diazomethane at −80 °C in hexane/CH2Cl2 afforded the expected 2-sulfanyl-2-isobutanoyl-2,5-dihydro-1,3,4-thiadiazole. After the addition of E-1a and warming of the mixture to room temperature, the corresponding thiolane as the
- this series the experimental results were confirmed by computational methods. In the reaction of diazomethane with E-1b in THF at room temperature 4,5-dihydro-3H-pyrazole 35 was detected as the initial [3 + 2]-cycloadduct by 1H NMR spectroscopy [29] (Scheme 11). Fast tautomerization led to the
Graphical Abstract
Figure 1: Dialkyl dicyanofumarates E-1 and dicyanomaleates Z-1.
Scheme 1: Methods for the synthesis of dialkyl dicyanofumarates E-1 from alkyl cyanoacetates 2.
Scheme 2: Methods for the synthesis of dialkyl dicyanofumarates E-1 from alkyl bromoacetates 3.
Scheme 3: Reaction of dimethyl dicyanofumarate (E-1b) with dimethoxycarbene [(MeO)2C:] generated in situ from...
Scheme 4: Cyclopropanation of diethyl dicyanofumarate (E-1a) through reaction with the thiophene derived sulf...
Scheme 5: Cyclopropanation of dimethyl dicyanofumarate (E-1b) through a stepwise reaction with the in situ ge...
Scheme 6: The [2 + 2]-cycloadditions of dimethyl dicyanofumarate (E-1b) with electron-rich ethylenes 20 and 22...
Scheme 7: The [2 + 2]-cycloaddition of isomeric dimethyl dicyanofumarate (E-1b) and dicyanomaleate (Z-1b) wit...
Scheme 8: Non-concerted [2 + 2]-cycloaddition between E-1b and bicyclo[2.1.0]pentene (27).
Scheme 9: Stepwise [3 + 2]-cycloadditions of some thiocarbonyl S-methanides with dialkyl dicyanofumarates E-1...
Scheme 10: Stepwise [3 + 2]-cycloadditions of dimethyl dicyanofumarate (E-1b) and dimethyl dicyanomaleate (Z-1b...
Scheme 11: [3 + 2]-Cycloaddition of diazomethane with dimethyl dicyanofumarate (E-1b) leading to 1H-pyrazole d...
Scheme 12: Reversible Diels–Alder reaction of fulvenes 36 with diethyl dicyanofumarate (E-1a).
Scheme 13: [4 + 2]-Cycloaddition of 9,10-dimethylanthracene (39b) and E-1a.
Scheme 14: Stepwise [4 + 2]-cycloaddition of dimethyl dicyanofumarate (E-1b) with electron-rich 1,1-dimethoxy-...
Scheme 15: Formal [4 + 2]-cycloaddition of 3,4-di(α-styryl)furan (47) with dimethyl dicyanofumarate (E-1b).
Scheme 16: Acid-catalyzed Michael addition of enolizable ketones of type 49 to E-1.
Scheme 17: Reaction of diethyl dicyanofumarate (E-1a) with ammonia NH3.
Scheme 18: Reaction of dialkyl dicyanofumarates E-1 with primary and secondary amines.
Scheme 19: Reaction of dialkyl dicyanofumarates E-1 with 1-azabicyclo[1.1.0]butanes 55.
Scheme 20: Formation of pyrazole derivatives in the reaction of hydrazines with E-1.
Scheme 21: Formation of 5-aminopyrazole-3,4-dicarboxylate 65 via heterocyclization reactions.
Scheme 22: Reactions of aryl- and hetarylcarbohydrazides 67 with E-1a.
Scheme 23: Multistep reaction leading to perhydroquinoxaline derivative 73.
Scheme 24: Synthesis of ethyl 7-aminopteridin-6-carboxylates 75 via a domino reaction.
Scheme 25: Synthesis of morhpolin-2-ones 80 from E-1 and β-aminoalcohols 78 through an initial aza-Michael add...
Scheme 26: Reaction of 3-amino-5-arylpyrazoles 81 with dialkyl dicyanofumarates E-1 via competitive nucleophil...
Scheme 27: Heterocyclization reaction of thiosemicarbazone 86 with E-1a.
Scheme 28: Formation of diethyl 4-cyano-5-oxotetrahydro-4H-chromene-3,4-dicarboxylate (90) from E-1a via heter...
Scheme 29: Reaction of dialkyl dicyanofumarates E-1 with cysteamine (92).
Scheme 30: Formation of disulfides through reaction of thiols with E-1a.
Scheme 31: Formation of CT salts of E-1 with Mn2+ and Cr2+ metallocenes through one-electron transfer.
Scheme 32: Oxidation of diethyl dicyanofumarate (E-1a) with H2O2 to give oxirane 101.
Scheme 33: The aziridination of E-1b through nitrene addition.
A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes
- Grzegorz Mlostoń,
- Paulina Pipiak,
- Róża Hamera-Fałdyga and
- Heinz Heimgartner
Beilstein J. Org. Chem. 2017, 13, 1900–1906, doi:10.3762/bjoc.13.185
- on [3 + 2]-cycloadditions with thioketones and diazo compounds, we turned our attention to hetaryl thioketones [18]. It turned out that the presence of the hetaryl groups strongly influences the reactivity of these dipolarophiles in reactions with diazomethane (CH2N2, Schönberg reaction) [19][20][21
- -trimethylsilyl-4,4,5,5-tetraaryl-1,3-dithiolanes, readily available by treatment of hetaryl thioketones with trimethylsilyl diazomethane (TMS-CHN2), are superior substrates for the preparation of tetraarylethenes. Another group of 2-trimethylsilylated 1,3-dithiolanes, obtained through the [3 + 2]-cycloaddition
- analysis in CDCl3 solution. The crude products were purified by column chromatography (petroleum ether/CH2Cl2, increasing polarity to CH2Cl2). Reactions of diphenyl and phenyl selenophen-2-yl thioketones with diazomethane (CH2N2; Sel = selenophen-2-yl). Reaction of diaryl thioketones with
Graphical Abstract
Scheme 1: Reactions of diphenyl and phenyl selenophen-2-yl thioketones with diazomethane (CH2N2; Sel = seleno...
Scheme 2: Reaction of diaryl thioketones with trimethylsilyldiazomethane (TMS-CHN2).
Scheme 3: Formation of tetraaryl/hetarylethenes 9 from the reaction of TMS-CHN2 with diaryl/hetaryl thioketon...
Scheme 4: Synthesis of dibenzofulvenes 9g–k.
Scheme 5: a) Mechanistic explanation for formation of ethenes 9 from dithiolanes of type 6 and b) desilylatio...
A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines
- Benedikt C. Melzer and
- Franz Bracher
Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156
- methylation protocol, we explored diazomethane, but no conversion was observed at all. Finally, all of the synthesized alkaloids were tested for their cytotoxic potential in a MTT assay on the HL-60 cell line. Except for menisporphine (2) and bianfugecine (6, both IC50 values > 50 µM), all of the described
Graphical Abstract
Figure 1: Prominent oxoaporphine and oxoisoaporphine alkaloids: liriodenine (1), menisporphine (2), dauriporp...
Scheme 1: Previously reported [7,17] and new approach to oxoisoaporphine alkaloids.
Scheme 2: Synthesis of iodinated isoquinolines 8a–c from alkoxy-substituted isoquinolines 7a–c.
Scheme 3: Synthesis of methyl 2-(isoquinolin-1-yl)benzoates 10a–c from 1-iodoisoquinolines 8a–c.
Scheme 4: Synthesis of the alkaloids 6-O-demethylmenisporphine (4), dauriporphinoline (5), and bianfugecine (6...
Scheme 5: Attempted synthesis of bianfugecine (6) via directed remote metalation and subsequent trapping of t...
Scheme 6: Outcome of a D2O quenching experiment after metalation of amide 12.
Scheme 7: Synthesis of 1-arylnaphthalene analogues 15 and 16.
Scheme 8: Outcome of a D2O quenching experiment after metalation of amide 16 with LDA.
Scheme 9: Synthesis of the alkaloids menisporphine (2) and dauriporphine (3) by O-methylation of the alkaloid...
Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study
- Michael L. McKee,
- Grzegorz Mlostoń,
- Katarzyna Urbaniak and
- Heinz Heimgartner
Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44
- , Winterthurerstrasse 190, CH-8057 Zurich, Switzerland 10.3762/bjoc.13.44 Abstract An intriguing stepwise diradical mechanism of the dimerization of the reactive intermediate (thiocarbonyl S-methanide) appearing in the reaction of phenyl selenophen-2-yl thioketone with diazomethane was studied by means of
- convenient access comprises the treatment of a C=S substrate with diazomethane or its derivatives. Depending on the substitution pattern, 2,5-dihydro-1,3,4-thiadiazoles 2 display different thermal stability. Whereas sterically bulky aliphatic substituents increase the temperature required for the
- pathway was excluded. Results and Discussion In a recent publication, reactions of hetaryl phenyl and dihetaryl thioketones with diazomethane have been described, and the formation of 1,3-dithiolanes as well as unexpected, hitherto unknown, dimers of the intermediate thiocarbonyl S-methanide was observed
Graphical Abstract
Scheme 1: Generation and typical reactions of the reactive dialkyl and diaryl thiocarbonyl S-methanides 1.
Figure 1: Structures of the reactive intermediates as a diradical 6 or a zwitterion 7 in the course of the di...
Scheme 2: The in situ generation of phenyl selenophen-2-yl S-methanide (8) and its competitive reactions: 1,3...
Figure 2: Potential 1,3-dipolar electrocyclization of thiocabonyl S-methanide 8A. Computed enthalpies (free e...
Figure 3: Stepwise radical dimerization of the reactive thiocarbonyl S-methanide 8. Computed enthalpies (free...
Figure 4: Potential competitive cyclization reactions of the intermediate diradical 12.
Figure 5: a) Spin densities in the conformers 12F and 12G of diradical 12. b) Heteroatom effect on the magnit...
