Search results
Search for "primary amine" in Full Text gives 169 result(s) in Beilstein Journal of Organic Chemistry.
Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones
- Pooja Goyal,
- Akhil K. Dubey,
- Raghunath Chowdhury and
- Amey Wadawale
Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136
- 10.3762/bjoc.20.136 Abstract The enantioselective 1,4-addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones catalyzed by a cinchona alkaloid-derived primary amine–Brønsted acid composite is reported. Both enantiomers of the anticipated pyrazole derivatives were obtained in good to excellent
- metal catalytic conditions. In continuation of our work in the field of organocatalysis [26][27][28][29], herein, we present the Michael addition reaction of 4-unsubstituted pyrazolin-5-ones with arylidene/heteroarylideneacetones using cinchona alkaloid-derived primary amine catalysts. The developed
- primary amine catalysts (see Table S1 in Supporting Information File 1) in toluene at room temperature (30–32 °C). When the test reaction was conducted in the presence of 15 mol % of 9-amino-9-deoxy-epicinchonidine (I) as catalyst [30] for 12 h and treated with Ac2O followed by DABCO, the reaction gave
Graphical Abstract
Figure 1: Selected examples of drugs and bioactive molecules bearing a pyrazole core.
Scheme 1: Representative examples of asymmetric organocatalytic conjugate addition of pyrazolin-5-ones to α,β...
Scheme 2: Scope of substrates. Reaction conditions: 1 (0.3 mmol), 2 (0.2 mmol), 15 mol % of catalyst I, 30 mo...
Scheme 3: Synthesis of pyrazole-benzofuran and pyrazole–indole hybrid molecules. Reaction conditions: 1m or 1n...
Scheme 4: Synthesis of 3aa on preparative scale.
Figure 2: Single crystal X-ray structure of ent-3ba (CCDC 2234286).
Scheme 5: Proposed reaction mechanism.
Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines
- Lu Li,
- Na Li,
- Xiao-Tian Mo,
- Ming-Wei Yuan,
- Lin Jiang and
- Ming-Long Yuan
Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130
- ; primary amine; Introduction Aniline derivatives possessing arylmethyl substituents at the ortho position are an important class of amines. They have a wide variety of practical applications, ranging from anti-depression [1], being δ receptor stimulants in analgesic pharmaceuticals [2], to antioxidant
Graphical Abstract
Scheme 1: Synthesis of aniline derivatives from 2-cyclohexenones or derivatives thereof.
Scheme 2: Synthesis of (E)-2-arylidene-3-cyclohexenones 2.
Scheme 3: Substrate scope of (E)-2-arylidene-3-cyclohexenones 2. Conditions: reactions were conducted with 2a...
Scheme 4: Substrate scope of primary amines 3. Conditions: reactions conducted with 2 (0.2 mmol) and 3b–y (2....
Scheme 5: Gram-scale reaction and successive one-pot synthesis.
Scheme 6: Synthetic manipulation.
Synthesis and characterization of water-soluble C60–peptide conjugates
- Yue Ma,
- Lorenzo Persi and
- Yoko Yamakoshi
Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71
- suitable for the coupling to peptides on resin, prepared by solid-phase peptide synthesis (SPPS) [35]. The detailed conditions for the amide-forming reaction were optimized using biscarboxylic acid-substituted C60 derivative 3 and a similar peptide with a primary amine derived from γ-aminobutyric acid
- on resin, a GABA residue was attached to the N-terminus of the peptide in order to provide a less-hindered primary amine, enabling an efficient amide conjugation reaction with biscarboxylic acid-substituted C60 derivative 3. Compound 3 was prepared by Prato reaction of C60 and an N-glycine derivative
Graphical Abstract
Figure 1: a) Synthesis of C60–oligopeptide conjugates 5a–c and b) synthesis of compound 3. Fulleropyrrolidine...
Figure 2: Structure of C60–oligo-Lys (5a), C60–oligo-Glu (5b), and C60–oligo-Arg (5c) and images of dissolved...
Figure 3: DLS diagrams of C60–peptide conjugates 5a (1 mM, in Milli-Q® water), 5b (1 mM, in Milli-Q® water or...
Figure 4: UV–vis spectra of C60–peptide conjugates 5a and 5b (20 μM in Milli-Q® water for 5a and in pH 9.0 TR...
Figure 5: 1H NMR spectrum of C60–peptide conjugate 5a in D2O (above) and of the precursor monoadduct in CDCl3...
Figure 6: 13C NMR spectrum of C60–peptide conjugate 5a in D2O and of the precursor monoadduct in CDCl3 at 150...
Figure 7: a) X-band ESR spectra of the 4-oxo-TEMP adduct with 1O2 generated by C60–oligo-Lys (5a) and rose be...
Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines
- Geng-Xin Liu,
- Xiao-Ting Jie,
- Ge-Jun Niu,
- Li-Sheng Yang,
- Xing-Lin Li,
- Jian Luo and
- Wen-Hao Hu
Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59
- also compatible with these mild conditions (4y–aa, 51–72%). Additionally, the diazo derivative of epiandrosterone was reactive in this protocol, giving the product 4ab in 59% yield. Delightedly, this procedure was successfully applied to aromatic amine (N-methylaniline), primary amine (aniline) and
Graphical Abstract
Scheme 1: Background (a and b) and proposed carboamination MCR with diazo esters (c). a) Selected bioactive γ...
Scheme 2: Substrate scope of diazo compounds, 1,3-dienes and amines. aReactions (1/2/3/Pd(OAc)2/Xantphos = 0....
Scheme 3: Substrate scope of diazo compounds, allenes and amines. aReactions (1/5/3/Pd(OAc)2/Xantphos = 0.3.0...
Scheme 4: Mechanistic experiments. a) Radical trapping experiments with TEMPO. b) Exclusion of possible inter...
Scheme 5: Proposed mechanisms for the carboamination of 1,3-dienes or allenes with diazo esters and amines.
Scheme 6: Scale-up reactions and synthetic transformations. Reaction conditions: a) LiAlH4, THF, 0 °C; b) MeM...
Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles
- Chuan Yang,
- Wei Shi,
- Jian Tian,
- Lin Guo,
- Yating Zhao and
- Wujiong Xia
Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12
- 52% (3p) yields, respectively. If the chains did not involve a carbonyl group, the yields were much lower (3q, 25%; 3s, 29%, and 3t, 29%). When a pyrrole ring was used instead of indole, the reaction proceeded but gave the product in low yield (3r). We did not explore the reaction with a primary
- amine functionalized substrate, because of competition of the reaction site during the synthesis of substrates. However, an amide-substituted indole furnished a clean product without competition; for example, product 3u was derived from melatonin with an amide functional group, whose reaction to the
Graphical Abstract
Figure 1: Representative dihydropyrido[1,2-a]indolone derivatives.
Scheme 1: Selected works for the construction of dihydropyrido[1,2-a]indolones and current methodology.
Scheme 2: Substrate scope of the cascade reaction.
Scheme 3: Radical trapping experiment.
Figure 2: UV–vis spectra of substrates; [1a] 0.33 M, [2a] 0.11 M.
Scheme 4: Plausible reaction mechanism.
α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping
- Angel Palillero-Cisneros,
- Paola G. Gordillo-Guerra,
- Fernando García-Alvarez,
- Olivier Jackowski,
- Franck Ferreira,
- Fabrice Chemla,
- Joel L. Terán and
- Alejandro Perez-Luna
Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103
- of primary amines and tert-butylsulfinamide (preparation of compounds 5–7 and 8a–c). In a round-bottomed flask under argon, n-BuLi (1.0 equiv, soln. in heptane) was added dropwise to a THF (0.2 mol·L−1) solution of the appropriate primary amine or tert-butylsulfinamide (1.0 equiv) at −55 °C. The
Graphical Abstract
Scheme 1: Air-promoted radical chain reaction of dialkylzinc reagents with α,β-unsaturated carbonyl compounds....
Scheme 2: Enolate formation by zinc radical transfer (SH2 on dialkylzinc reagents).
Scheme 3: Preparation of α-(aminomethyl)acrylate 10.
Scheme 4: Reaction of α-(aminomethyl)acrylate 10 with Et2Zn in the presence of air.
Scheme 5: Chemical correlation to determine the configuration of the major diastereomer of (RS)-14b.
Scheme 6: Air-promoted tandem 1,4-addition–aldol condensation reactions of Et2Zn with α-(aminomethyl)acrylate...
Scheme 7: Diagnostic experiments for a radical mechanism and for enolate formation.
Scheme 8: Diagnostic experiments with N-benzyl enoate 10.
Scheme 9: Reactivity manifolds for the air-promoted tandem 1,4-addition–electrophilic substitution reaction b...
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...
Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update
- Anup Biswas
Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72
- stereocenter bearing primary amine and trifluoromethyl functionalities associated with appreciable enantiocontrol. The substrate scope was investigated by the variation of sterically and electronically divergent aryl substituents in the ketimines but the enantioselectivity was markedly lowered with sterically
- after recrystallization. Subsequent ozonolysis of the terminal alkene functionality with a follow-up reduction furnished primary alcohol 134 which was transformed into the azide 135. Reduction of the azide 135 was accompanied by debenzylation, was followed by tosylation of the primary amine and exchange
Graphical Abstract
Scheme 1: First organocatalyzed asymmetric aza-Friedel–Crafts reaction.
Scheme 2: Aza-Friedel–Crafts reaction between indoles and cyclic ketimines.
Scheme 3: Aza-Friedel–Crafts reaction utilizing trifluoromethyldihydrobenzoazepinoindoles as electrophiles.
Scheme 4: Aza-Friedel–Crafts reaction utilizing cyclic N-sulfimines as electrophiles.
Scheme 5: Aza-Friedel–Crafts reaction involving N-unprotected imino ester as electrophile.
Scheme 6: Aza-Friedel–Crafts and lactonization cascade.
Scheme 7: One-pot oxidation and aza-Friedel–Crafts reaction.
Scheme 8: C1 and C2-symmetric phosphoric acids as catalysts.
Scheme 9: Aza-Friedel–Crafts reaction using Nps-iminophosphonates as electrophiles.
Scheme 10: Aza-Friedel–Crafts reaction between indole and α-iminophosphonate.
Scheme 11: [2.2]-Paracyclophane-derived chiral phosphoric acids as catalyst.
Scheme 12: Aza-Friedel–Crafts reaction through ring opening of sulfamidates.
Scheme 13: Isoquinoline-1,3(2H,4H)-dione scaffolds as electrophiles.
Scheme 14: Functionalization of the carbocyclic ring of substituted indoles.
Scheme 15: Aza-Friedel–Crafts reaction between unprotected imines and aza-heterocycles.
Scheme 16: Anilines and α-naphthols as potential nucleophiles.
Scheme 17: Solvent-controlled regioselective aza-Friedel–Crafts reaction.
Scheme 18: Generating central and axial chirality via aza-Friedel–Crafts reaction.
Scheme 19: Reaction between indoles and racemic 2,3-dihydroisoxazol-3-ol derivatives.
Scheme 20: Exploiting 5-aminoisoxazoles as nucleophiles.
Scheme 21: Reaction between unsubstituted indoles and 3-alkynylated 3-hydroxy-1-oxoisoindolines.
Scheme 22: Synthesis of unnatural amino acids bearing an aza-quaternary stereocenter.
Scheme 23: Atroposelective aza-Friedel–Crafts reaction.
Scheme 24: Coupling of 5-aminopyrazole and 3H-indol-3-ones.
Scheme 25: Pyrophosphoric acid-catalyzed aza-Friedel–Crafts reaction on phenols.
Scheme 26: Squaramide-assisted aza-Friedel–Crafts reaction.
Scheme 27: Thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 28: Squaramide-catalyzed reaction between β-naphthols and benzothiazolimines.
Scheme 29: Thiourea-catalyzed reaction between β-naphthol and isatin-derived ketamine.
Scheme 30: Quinine-derived molecule as catalyst.
Scheme 31: Cinchona alkaloid as catalyst.
Scheme 32: aza-Friedel–Crafts reaction by phase transfer catalyst.
Scheme 33: Disulfonamide-catalyzed reaction.
Scheme 34: Heterogenous thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 35: Total synthesis of (+)-gracilamine.
Scheme 36: Total synthesis of (−)-fumimycin.
Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach
- Dileep Kumar Singh and
- Rajesh Kumar
Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71
- proposed by Wang [55] (Scheme 2b), 2,5-dimethoxytetrahydrofuran (2) is first protonated with acetic acid, followed by ring opening to form carbocation B. In the following step, primary amine 1 nucleophilically attacks carbocation B to produce intermediate C, which, after proton rearrangement and the
Graphical Abstract
Figure 1: Various pyrrole containing molecules.
Scheme 1: Various synthestic protocols for the synthesis of pyrroles.
Figure 2: A tree-diagram showing various conventional and green protocols for Clauson-Kaas pyrrole synthesis.
Scheme 2: A general reaction of Clauson–Kaas pyrrole synthesis and proposed mechanism.
Scheme 3: AcOH-catalyzed synthesis of pyrroles 5 and 7.
Scheme 4: Synthesis of N-substituted pyrroles 9.
Scheme 5: P2O5-catalyzed synthesis of N-substituted pyrroles 11.
Scheme 6: p-Chloropyridine hydrochloride-catalyzed synthesis of pyrroles 13.
Scheme 7: TfOH-catalyzed synthesis of N-sulfonylpyrroles 15, N-sulfonylindole 16, N-sulfonylcarbazole 17.
Scheme 8: Scandium triflate-catalyzed synthesis of N-substituted pyrroles 19.
Scheme 9: MgI2 etherate-catalyzed synthesis and proposed mechanism of N-arylpyrrole derivatives 21.
Scheme 10: Nicotinamide catalyzed synthesis of pyrroles 23.
Scheme 11: ZrOCl2∙8H2O catalyzed synthesis and proposed mechanism of pyrrole derivatives 25.
Scheme 12: AcONa catalyzed synthesis of N-substituted pyrroles 27.
Scheme 13: Squaric acid-catalyzed synthesis and proposed mechanism of N-substituted pyrroles 29.
Figure 3: Reusability of catalyst γ-Fe2O3@SiO2-Sb-IL in six cycles.
Scheme 14: Magnetic nanoparticle-supported antimony catalyst used in the synthesis of N-substituted pyrroles 31...
Scheme 15: Iron(III) chloride-catalyzed synthesis of N-substituted pyrroles 33.
Scheme 16: Copper-catalyzed Clauson–Kaas synthesis and mechanism of pyrroles 35.
Scheme 17: β-CD-SO3H-catalyzed synthesis and proposed mechanism of pyrroles 37.
Figure 4: Recyclability of β-cyclodextrin-SO3H.
Scheme 18: Solvent-free and catalyst-free synthesis and plausible mechanism of N-substituted pyrroles 39.
Scheme 19: Nano-sulfated TiO2-catalyzed synthesis of N-substituted pyrroles 41.
Figure 5: Plausible mechanism for the formation of N-substituted pyrroles catalyzed by nano-sulfated TiO2 cat...
Scheme 20: Copper nitrate-catalyzed Clauson–Kaas synthesis and mechanism of N-substituted pyrroles 43.
Scheme 21: Synthesis of N-substituted pyrroles 45 by using Co catalyst Co/NGr-C@SiO2-L.
Scheme 22: Zinc-catalyzed synthesis of N-arylpyrroles 47.
Scheme 23: Silica sulfuric acid-catalyzed synthesis of pyrrole derivatives 49.
Scheme 24: Bismuth nitrate-catalyzed synthesis of pyrroles 51.
Scheme 25: L-(+)-tartaric acid-choline chloride-catalyzed Clauson–Kaas synthesis and plausible mechanism of py...
Scheme 26: Microwave-assisted synthesis of N-substituted pyrroles 55 in AcOH or water.
Scheme 27: Synthesis of pyrrole derivatives 57 using a nano-organocatalyst.
Figure 6: Nano-ferric supported glutathione organocatalyst.
Scheme 28: Microwave-assisted synthesis of N-substituted pyrroles 59 in water.
Scheme 29: Iodine-catalyzed synthesis and proposed mechanism of pyrroles 61.
Scheme 30: H3PW12O40/SiO2-catalyzed synthesis of N-substituted pyrroles 63.
Scheme 31: Fe3O4@-γ-Fe2O3-SO3H-catalyzed synthesis of pyrroles 65.
Scheme 32: Mn(NO3)2·4H2O-catalyzed synthesis and proposed mechanism of pyrroles 67.
Scheme 33: p-TsOH∙H2O-catalyzed (method 1) and MW-assisted (method 2) synthesis of N-sulfonylpyrroles 69.
Scheme 34: ([hmim][HSO4]-catalyzed Clauson–Kaas synthesis of pyrroles 71.
Scheme 35: Synthesis of N-substituted pyrroles 73 using K-10 montmorillonite catalyst.
Scheme 36: CeCl3∙7H2O-catalyzed Clauson–Kaas synthesis of pyrroles 75.
Scheme 37: Synthesis of N-substituted pyrroles 77 using Bi(NO3)3∙5H2O.
Scheme 38: Oxone-catalyzed synthesis and proposed mechanism of N-substituted pyrroles 79.
B–N/B–H Transborylation: borane-catalysed nitrile hydroboration
- Filip Meger,
- Alexander C. W. Kwok,
- Franziska Gilch,
- Dominic R. Willcox,
- Alex J. Hendy,
- Kieran Nicholson,
- Andrew D. Bage,
- Thomas Langer,
- Thomas A. Hunt and
- Stephen P. Thomas
Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138
- , 95%) groups were tolerated under the reaction conditions. The presence of a primary amine in the substrate was tolerated under the reaction conditions (1o), undergoing efficient hydroboration to give the dihydrochloride salt (87%), although an increase in HBpin equivalents (5.5 equiv) was required
Graphical Abstract
Scheme 1: a) Derivatives of primary amines in materials chemistry, pharmaceuticals, and agrochemicals; b) thi...
Scheme 2: Substrate scope of borane-catalysed nitrile hydroboration with HBpin. Conditions: nitrile (0.50 mmo...
Scheme 3: a) Proposed mechanism; b) H-B-9-BBN-catalysed heptanenitrile hydroboration (yield determined by 1H ...
Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides
- Jiaxi Xu
Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90
- synthetic method showed very limited substrate scope. Only less bulky primary amines underwent the first aza-Michael addition and then intramolecular nucleophilic substitution. However, aromatic amines, aniline, 2,3-dihydro-1H-inden-4-amine, and the bulky aliphatic primary amine adamantylamine did not
Graphical Abstract
Figure 1: Biologically active 1,2-azaphospholine 2-oxide derivatives.
Figure 2: Diverse synthetic strategies for the preparation of 1,2-azaphospholidine and 1,2-azaphospholine 2-o...
Scheme 1: Synthesis of 1-phenyl-2-phenylamino-γ-phosphonolactam (2) from N,N’-diphenyl 3-chloropropylphosphon...
Scheme 2: Synthesis of 2-ethoxy-1-methyl-γ-phosphonolactam (6) from ethyl N-methyl-(3-bromopropyl)phosphonami...
Scheme 3: Synthesis of 2-aryl-1-methyl-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 13 from N-aryl-2-chlorom...
Scheme 4: Synthesis of 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides from alkylarylphosphinyl or diarylphosph...
Scheme 5: Synthesis of 3-arylmethylidene-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides via the TBAF-mediated ...
Scheme 6: Synthesis of 2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides via the metal-free intramolecular oxida...
Scheme 7: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 42 and 44 from ethyl/benzyl 2-bromobenzy...
Scheme 8: Synthesis of azaphospholidine 2-oxides/sulfide from 1,2-oxaphospholane 2-oxides/sulfides and 1,2-th...
Scheme 9: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides/sulfides from 2-aminobenzyl(phenyl)phosp...
Scheme 10: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfide (59) from zwitterionic 2-aminobenzyl(ph...
Scheme 11: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides from 2-aminobenzyl(methyl/phenyl)phosphi...
Scheme 12: Synthesis of ethyl 2-methyl-1,2-azaphospholidine-5-carboxylate 2-oxide 69 from 2-amino-4-(hydroxy(m...
Scheme 13: Synthesis of 2-methoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxide 71 from dimethyl 2-(methylamino...
Scheme 14: Synthesis of tricyclic γ-phosphonolactams via formation of the P–C bond.
Scheme 15: Synthesis of γ-phosphonolactams 85 from ethyl 2-(3-chloropropyl)aminoalkanoates with diethyl chloro...
Scheme 16: Synthesis of N-phosphoryl- and N-thiophosphoryl-1,2-azaphospholidine 2-oxides 90/2-sulfides 91 from...
Scheme 17: Synthesis of 1-methyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 56a and 93 from P-(chloromethyl...
Scheme 18: Synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N’-diallyl-vinylphosphonodia...
Scheme 19: Diastereoselective synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N’-dially...
Scheme 20: Synthesis of 1-alkyl-3-benzoyl-2-ethoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 106 from ethy...
Scheme 21: Synthesis of cyclohexadiene-fused γ-phosphinolactams from diphenyl-N-benzyl-N-methylphosphinamide (...
Scheme 22: Synthesis of cyclohexadiene-fused γ-phosphinolactams from diphenyl-N-alkyl-N-benzylphosphinamides.
Scheme 23: Synthesis of cyclohexadiene-fused γ-phosphinolactams from diphenyl-N-methyl-N-(1-phenylethyl)phosph...
Scheme 24: Synthesis of benzocyclohexadiene-fused γ-phosphinolactams from dinaphth-1-yl-N-alkyl-N-benzylphosph...
Scheme 25: Synthesis of benzocyclohexadiene-fused γ-phosphinolactams from dinaphth-1-yl-N-benzyl-N-methylphosp...
Scheme 26: Synthesis of carbonyl-containing benzocyclohexadiene-fused γ-phosphinolactams from dinaphth-1-yl-N-...
Scheme 27: Synthesis of benzocyclohexadiene-fused γ-phosphinolactams from dinaphthyl-N-benzyl-N-methylphosphin...
Scheme 28: Synthesis of cyclohexadiene-fused 1-(N-benzyl-N-methyl)amino-γ-phosphinolactams from aryl-N,N’-dibe...
Scheme 29: Synthesis of bis(cyclohexadiene-fused γ-phosphinolactam)s from bis(diphenyl-N-benzylphosphinamide)s....
Scheme 30: Synthesis of bis(hydroxymethyl-derived cyclohexadiene-fused γ-phosphinolactam)s from tetramethylene...
Scheme 31: Synthesis of 2-aryl/dimethylamino-1-ethoxy-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides from ethy...
Scheme 32: Synthesis of ethyl 2-ethoxy-1,2-azaphospholidine-4-carboxylate 2-oxides from ethyl 2-((chloro(ethox...
Scheme 33: Synthesis of (1S,3R)-2-(tert-butyldiphenylsilyl)-3-methyl-1-phenyl-2,3-dihydrobenzo[c][1,2]azaphosp...
Scheme 34: Synthesis of 2,3,3a,9a-tetrahydro-4H-1,2-azaphospholo[5,4-b]chromen-4-one (215) from 3-(phenylamino...
Scheme 35: Synthesis of quinoline-fused 1,2-azaphospholine 2-oxides from 2-azidoquinoline-3-carbaldehydes and ...
Scheme 36: Synthesis of 1-hydro-1,2-azaphosphol-5-one 2-oxide from cyanoacetohydrazide with phosphonic acid an...
Scheme 37: Synthesis of chromene-fused 5-oxo-1,2-azaphospolidine 2-oxides.
Scheme 38: Synthesis of (R)-1-phenyl-2-((R)-1-phenylethyl)-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxide (239)...
Scheme 39: Synthesis of dihydro[1,2]azaphosphole 1-oxides from aryl/vinyl-N-phenylphosphonamidates and aryl-N-...
Scheme 40: Synthesis of 1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxides.
First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation
- Maxime Pypec,
- Laurent Jouffret,
- Claude Taillefumier and
- Olivier Roy
Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85
- ]. Beyond their resemblance to peptides, the obvious interest in this family of peptidomimetics arises from their ease of synthesis by the modular submonomer protocol [9] which enables the incorporation of numerous primary amine synthons in a sequence-controlled manner [10], and application of solid
Graphical Abstract
Figure 1: (A) Summary of the main side chains exerting significant steric and/or electronic effects and influ...
Figure 2: Solution-phase synthesis of N-(methylamino)glycine oligomers using N-Boc-N-methylhydrazine as a sub...
Scheme 1: Submonomer synthesis used for the construction of peptoids 1–5 containing N-methylamino side chains...
Scheme 2: Evaluation of the efficiency of mixed anhydride methods by coupling of 1a and 1c.
Scheme 3: (3 + 3) segment coupling of trimers 3-OH onto trimer hydrazine 3a.
Figure 3: X-ray crystal structure of peptoid dimer 2: (A) single molecule; (B) unit cell, view along b axis (...
Figure 4: NOE effect interaction observed in the 2D-NOESY spectra of monomer 1 and dimer 2 in DMSO-d6.
Figure 5: Comparison of monomers A and B with respect to their ability to form intramolecular and intermolecu...
Figure 6: Model structure of N-(NMe)glycine peptoid. (A) dimer in the repeating (pp) conformation; (B) dimer ...
Mechanochemical halogenation of unsymmetrically substituted azobenzenes
- Dajana Barišić,
- Mario Pajić,
- Ivan Halasz,
- Darko Babić and
- Manda Ćurić
Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69
- dichlorinated regioisomers (L5Cl-I and L5Cl-II) (Scheme 1 and Table 1, entry 4). The chlorination of L3 substrate with a primary amine as substituent gave the monochlorinated product L3Cl-I in 46% yield, while the yields of L4Cl-I and L5Cl-I were 85% and 83%, respectively (Table 1, entries 2–4). Although both
Graphical Abstract
Figure 1: Molecular structures of the monomeric cyclopalladated intermediate and brominated product observed ...
Scheme 1: Halogenation of azobenzenes with strong electron-donating substituents.
Figure 2: a) Two-dimensional (2D) plot of the time-resolved Raman monitoring of NG of L2 (0.50 mmol) with NBS...
Figure 3: Experimental X-ray molecular structure of succinimide product L4-III.
Scheme 2: PdII-catalyzed halogenation of azobenzene and its para-halogenated derivatives.
Figure 4: Experimental X-ray molecular structure of the intermediate I6-I.
Figure 5: a) In situ observation of I6-I during the time-resolved Raman monitoring of LAG of L6 (0.50 mmol) w...
Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions
- Soumyadip Basu,
- Sauvik Chatterjee,
- Suman Ray,
- Suvendu Maity,
- Prasanta Ghosh,
- Asim Bhaumik and
- Chhanda Mukhopadhyay
Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14
- in the literature, which generally involve four components. These include one primary amine, two multiple bonds, and one aldehyde function [27]. However, one advantage of our study is that we only used three components since the cinnamaldehyde derivatives 3 played the role of two components at the
- mechanism for the synthesis of C5–C6-unsubstituted 1,4-DHPs is described in Scheme 1. The reaction initiates with the formation of an enamine moiety (see A) by the reaction of a primary amine 1 and a but-2-ynedioate 2. We isolated the intermediate A in the form of 4fA [30], corresponding to compound 4f, and
- vacuum at 60 °C. The synthesized pure Ni–chitosan nanocatalyst was characterized by powder FTIR and XRD spectroscopy, TEM, FESEM, and EDX analysis. Preparation of 1,4-dihydropyridine-2,3-dicarboxylate derivatives A primary amine 1 (1 mmol), a dialkyl but-2-ynedioate 2 (1 mmol), a cinnamaldehyde 3 (1 mmol
Graphical Abstract
Figure 1: FTIR spectra of (a) the Ni–chitosan NPs and (b) bare chitosan.
Figure 2: PXRD data for the Ni–chitosan NPs.
Figure 3: TEM (a and b) and SEM images (c and d) of the Ni–chitosan NPs.
Figure 4: EDX spectrum of the Ni–chitosan NPs.
Figure 5: Synthesis of dialkyl 1,4-dihydropyridine-2,3-dicarboxylate derivatives.
Figure 6: ORTEP representation of product 4a (CCDC 1949329).
Scheme 1: A plausible mechanistic route for the synthesis of C5–C6-unsubstituted 1,4-DHP derivatives using th...
Figure 7: Recycling experiment of the Ni–chitosan nanocatalyst.
Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases
- Inaiá O. Rocha,
- Yuri G. Kappenberg,
- Wilian C. Rosa,
- Clarissa P. Frizzo,
- Nilo Zanatta,
- Marcos A. P. Martins,
- Isadora Tisoco,
- Bernardo A. Iglesias and
- Helio G. Bonacorso
Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191
- base; Introduction Schiff bases are an important class of organic compounds first reported by the German chemist Hugo Schiff in 1864 and are formed from the reversible condensation between a primary amine and an aldehyde or a ketone [1]. Also known as azomethines, aldimines, and more commonly as
Graphical Abstract
Figure 1: Examples of structures and properties of Schiff bases of interest in the present study.
Scheme 1: General view for the present study.
Scheme 2: Synthesis of ((trifluoromethyl)quinolinyl)phenol Schiff bases 3aa–fa.
Scheme 3: Synthesis of trifluoromethylated quinolinyl-phenol Schiff bases 3bb–be.
Figure 2: ORTEP diagram of the crystal structure of (E)-2-(((2-phenyl-4-(trifluoromethyl)quinolin-6-yl)imino)...
Figure 3: Normalized absorption spectra in the UV–vis region of compounds (a) 3ea and (b) 3be in CHCl3, MeOH ...
Figure 4: Normalized steady-state fluorescence emission spectra of compound 3aa (R = Ph, R1 = H) in CHCl3 (bl...
Figure 5: Comparative normalized steady-state fluorescence emission spectra of compounds 3bb and 3be in the t...
Figure 6: Photostability (%) plots of derivatives 3aa–fa and 3bb–be in DMSO solution after irradiation with w...
Figure 7: DPBF photooxidation assays by red-light irradiation with diode laser (λ = 660 nm) in the presence o...
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
- Umesh P. Aher,
- Dhananjai Srivastava,
- Girij P. Singh and
- Jayashree B. S
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone
- Ilya A. P. Jourjine,
- Lukas Zeisel,
- Jürgen Krauß and
- Franz Bracher
Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181
- cyclization of primary alcohols like 2k has been successfully utilized in the synthesis of fluorenones and azafluorenones [37], however, the authors used TBHP in n-decane. We repeated the reaction for primary amine 2a, primary alcohol 2k, as well as aldehyde 2l with TBHP in n-decane and obtained fluorenone (3
- a yield of 62% employing TBHPaq and the Studer group [55] achieved, with a ring-methylated analogue, up to 72% with TBHP in decane and FeCp2 as initiator. Laha et al. [37] cyclized biphenyl-2-methanol (2k) in 70% yield using TBHP in decane/tetrabutylammonium iodide. Primary amine 2a was chosen as
- (Scheme 5 and Scheme 6). First, the three primary amines 15a–c with the same substitution patterns as reported for the secondary amines 9a–c (Scheme 4) were reacted under the standard conditions. While the yield for fluorenone 10b starting from primary amine 15b1 (40%) is slightly higher compared to its
Graphical Abstract
Scheme 1: Selected fluorenone-type natural products.
Scheme 2: Overview of published cyclization methodologies for the synthesis of fluorenones starting from func...
Scheme 3: Preliminary considerations for the oxidative cyclization of 2-(aminomethyl)biphenyls to fluorenones....
Scheme 4: Substrate scope and yields for oxidative cyclizations of N-methyl-2-(aminomethyl)biphenyls 9a–d bea...
Scheme 5: Substrate scope for the oxidative cyclization of 2-(aminomethyl)biphenyls. Conditions: a) Boc2O, NEt...
Scheme 6: Substrate scope for the oxidative cyclization of 2-(aminomethyl)biphenyls with main focus on protec...
Scheme 7: Total synthesis of nobilone (1d). Conditions: a) TBS-Cl, imidazole, DMF, 50 °C, 18 h; b) n-BuLi, B(...
Scheme 8: Proposed mechanism for the oxidative cyclization of amines 2a and 2b to fluorenone (3).
Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides
- Pratibha Sharma,
- Raakhi Gupta and
- Raj K. Bansal
Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173
- al. reported cinchona-based primary amine catalyzed cascade aza-Michael-aldol reaction of α,β-unsaturated ketones 6 with 2-(1H-pyrrol-2-yl)-2-oxoacetates 5 where triphenylacetic acid was used as an additive. This cascade reaction afforded highly functionalized chiral pyrrolizines 8 in good yields (70
Graphical Abstract
Scheme 1: Asymmetric aza-Michael addition catalyzed by cinchona alkaloid derivatives.
Scheme 2: Intramolecular 6-exo-trig aza-Michael addition reaction.
Scheme 3: Asymmetric aza-Michael/Michael addition cascade reaction of 2-nitrobenzofurans and 2-nitrobenzothio...
Scheme 4: Asymmetric aza-Michael addition of para-dienone imide to benzylamine.
Scheme 5: Asymmetric synthesis of chiral N-functionalized heteroarenes.
Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing
- Luke O. Jones,
- Leah Williams,
- Tasmin Boam,
- Martin Kalmet,
- Chidubem Oguike and
- Fiona L. Hatton
Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171
- interactions between anionic sulphate groups and the primary amine group present in doxorubicin which confers a positive charge under physiological conditions. This interaction was confirmed by in silico modelling. While the carriers did not show any cytotoxicity, cell viability was reduced in the presence of
Graphical Abstract
Figure 1: Schematic representation of the process of aqueous cryogel formation, using (a) monomers/small mole...
Figure 2: Microarchitecture of gelatin cryogels. (A) Surface and cross-sectional SEM micrographs of highly po...
Figure 3: Principle of 3D-cryogel printing. A) Illustration of 3D-printing of cryogels. B) Illustration of th...
Figure 4: Illustration of the production of the injectable multifunctional composite, comprised of alginate c...
Figure 5: Digital and SEM photographs of PETEGA cryogel at 20 °C (top) and 50 °C (bottom), synthesised via UV...
Figure 6: Cell morphology of T47D breast cancer cells cultured in HA cryogels. (A) Schematic representation o...
Figure 7: Preparation of PDMA/β-CD cryogel via cryogenic treatment and photochemical crosslinking in frozen s...
Figure 8: (A) Healing rate of wounds treated with autoclaved CG11 cryogels and those treated with 70% ethanol...
Figure 9: In vivo haemostatic capacity evaluation of the cryogels. Blood loss (a) and haemostatic time (b) in...
Asymmetric organocatalyzed synthesis of coumarin derivatives
- Natália M. Moreira,
- Lorena S. R. Martelli and
- Arlene G. Corrêa
Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128
- addition of 4-hydroxycoumarin (1) by the Re face of the enones 2 through a bifunctional modified binaphthyl organocatalyst 18 with primary amine [37]. The reaction occurs through the activation of the enone substrate by formation of an iminium ion intermediate and, in the presence of an acid additive
- enantioselective Michael addition of ketones 20 to 3-aroylcoumarins 19 [38]. For this transformation, the authors used a cinchona alkaloid-derived primary amine catalyst 22 (Scheme 6a). The study was performed with cyclic and acyclic ketones 20 and various 3-aroylcoumarins 19 and the desired products 21 were
- gram-scale experiment, affording the desired product 21a with excellent yield and ee (Scheme 6b). Ren et al. reported an enantioselective reaction of cyclopent-2-enone-derived Morita–Baylis–Hillman (MBH) alcohols 24 with 4-hydroxycoumarins 1 catalyzed by a chiral primary amine derived from
Graphical Abstract
Figure 1: Coumarin-derived commercially available drugs.
Figure 2: Inhibition of acetylcholinesterase by coumarin derivatives.
Scheme 1: Michael addition of 4-hydroxycoumarins 1 to α,β‐unsaturated enones 2.
Scheme 2: Organocatalytic conjugate addition of 4-hydroxycoumarin 1 to α,β-unsaturated aldehydes 2 followed b...
Scheme 3: Synthesis of 3,4-dihydrocoumarin derivatives 10 through decarboxylative and dearomatizative cascade...
Scheme 4: Total synthesis of (+)-smyrindiol (17).
Scheme 5: Michael addition of 4-hydroxycoumarin (1) to enones 2 through a bifunctional modified binaphthyl or...
Scheme 6: Michael addition of ketones 20 to 3-aroylcoumarins 19 using a cinchona alkaloid-derived primary ami...
Scheme 7: Enantioselective reaction of cyclopent-2-enone-derived MBH alcohols 24 with 4-hydroxycoumarins 1.
Scheme 8: Sequential Michael addition/hydroalkoxylation one-pot approach to annulated coumarins 28 and 30.
Scheme 9: Michael addition of 4-hydroxycoumarins 1 to enones 2 using a binaphthyl diamine catalyst 31.
Scheme 10: Asymmetric Michael addition of 4-hydroxycoumarin 1 with α,β-unsaturated ketones 2 catalyzed by a ch...
Scheme 11: Catalytic asymmetric β-C–H functionalization of ketones via enamine oxidation.
Scheme 12: Enantioselective synthesis of polycyclic coumarin derivatives 37 catalyzed by an primary amine-imin...
Scheme 13: Allylic alkylation reaction between 3-cyano-4-methylcoumarins 39 and MBH carbonates 40.
Scheme 14: Enantioselective synthesis of cyclopropa[c]coumarins 45.
Scheme 15: NHC-catalyzed lactonization of 2-bromoenals 46 with 4-hydroxycoumarin (1).
Scheme 16: NHC-catalyzed enantioselective synthesis of dihydrocoumarins 51.
Scheme 17: Domino reaction of enals 2 with hydroxylated malonate 53 catalyzed by NHC 55.
Scheme 18: Oxidative [4 + 2] cycloaddition of enals 57 to coumarins 56 catalyzed by NHC 59.
Scheme 19: Asymmetric [3 + 2] cycloaddition of coumarins 43 to azomethine ylides 60 organocatalyzed by quinidi...
Scheme 20: Synthesis of α-benzylaminocoumarins 64 through Mannich reaction between 4-hydroxycoumarins (1) and ...
Scheme 21: Asymmetric addition of malonic acid half-thioesters 67 to coumarins 66 using the sulphonamide organ...
Scheme 22: Enantioselective 1,4-addition of azadienes 71 to 3-homoacyl coumarins 70.
Scheme 23: Michael addition/intramolecular cyclization of 3-acylcoumarins 43 to 3-halooxindoles 74.
Scheme 24: Enantioselective synthesis of 3,4-dihydrocoumarins 78 catalyzed by squaramide 73.
Scheme 25: Organocatalyzed [4 + 2] cycloaddition between 2,4-dienals 79 and 3-coumarincarboxylates 43.
Scheme 26: Enantioselective one-pot Michael addition/intramolecular cyclization for the synthesis of spiro[dih...
Scheme 27: Michael/hemiketalization addition enantioselective of hydroxycoumarins (1) to: (a) enones 2 and (b)...
Scheme 28: Synthesis of 2,3-dihydrofurocoumarins 89 through Michael addition of 4-hydroxycoumarins 1 to β-nitr...
Scheme 29: Synthesis of pyrano[3,2-c]chromene derivatives 93 via domino reaction between 4-hydroxycoumarins (1...
Scheme 30: Conjugated addition of 4-hydroxycoumarins 1 to nitroolefins 95.
Scheme 31: Michael addition of 4-hydroxycoumarin 1 to α,β-unsaturated ketones 2 promoted by primary amine thio...
Scheme 32: Enantioselective synthesis of functionalized pyranocoumarins 99.
Scheme 33: 3-Homoacylcoumarin 70 as 1,3-dipole for enantioselective concerted [3 + 2] cycloaddition.
Scheme 34: Synthesis of warfarin derivatives 107 through addition of 4-hydroxycoumarins 1 to β,γ-unsaturated α...
Scheme 35: Asymmetric multicatalytic reaction sequence of 2-hydroxycinnamaldehydes 109 with 4-hydroxycoumarins ...
Scheme 36: Mannich asymmetric addition of cyanocoumarins 39 to isatin imines 112 catalyzed by the amide-phosph...
Scheme 37: Enantioselective total synthesis of (+)-scuteflorin A (119).
Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides
- Mathias B. Danielsen and
- Jesper Wengel
Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125
- siRNA had better eGFP gene silencing activity compared to the control siRNA with a single 2’-OMe RNA monomer near the 5’-end [77]. Conversion of the primary amine on the aminopropyl modification into a tertiary amine (monomer 36) and insertion four times in a 16-mer ON (two in the middle and one near
- attempt to introduce high yielding phosphoramidite building blocks suitable for automated ON synthesis, 2′-O-aminoethoxymethyl and 2′-O-aminopropoxymethyl nucleotides were developed. This method introduced the primary amine functionality through an azide reduction [73]. The corresponding monomers 37 and
Graphical Abstract
Figure 1: A schematic representation of 16-mer ASOs in different designs. White circles represent unmodified ...
Figure 2: Structures of 5-(1-propargylamino)-2’-deoxyuridine (A) and 2’-aminoethoxy-5-propargylaminouridine (...
Total synthesis of ent-pavettamine
- Memory Zimuwandeyi,
- Manuel A. Fernandes,
- Amanda L. Rousseau and
- Moira L. Bode
Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99
- ; pavettamine; polyamine; Introduction The identification and first reported synthesis of pavettamine (1) heralded the arrival of a novel and uniquely hydroxylated polyamine (PA) (Figure 1) [1]. In general, polyamines are described as aliphatic organic compounds with two or more primary amine substituents
Graphical Abstract
Figure 1: Structure of pavettamine 1 and its enantiomer 2.
Scheme 1: Established route for the synthesis of intermediate 4 [1].
Scheme 2: Alternative route. Reaction conditions: a) TrCl, pyridine, rt, overnight, 100%; b) DMAP, imidazole,...
Figure 2: Crystal structure of compound 9.
Scheme 3: Sequence showing the source of compound 9.
Scheme 4: Stereoselective reduction of intermediate 8 as key step towards intermediate 4. Reaction conditions...
Figure 3: Single crystal X-ray structure of compound 4.
Scheme 5: Synthesis of the C5 fragments from intermediate 4. Reaction conditions: a) i) TFAA, collidine, 0 °C...
Scheme 6: Synthesis of ent-pavettamine as the TFA salt 28. Reaction conditions: a) IBX, DMSO, rt, overnight, ...
Icilio Guareschi and his amazing “1897 reaction”
- Gian Cesare Tron,
- Alberto Minassi,
- Giovanni Sorba,
- Mara Fausone and
- Giovanni Appendino
Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93
- reaction reported in 1898 [50]. It involves the reaction of a β-dicarbonyl (ester or diketone) with a primary amine or ammonia and a cyanoacetic ester. The mechanism of this condensation closely resembles the three-component version of the Hantzsch pyridine synthesis and generates 6-hydroxypyridones. Also
Graphical Abstract
Figure 1: Icilio Guareschi (1847–1918). (Source: Annali della Reale Accademia di Agricoltura di Torino 1919, ...
Scheme 1: Vitamin B6 (pyridoxine, 1), gabapentin (2), and thymol (3).
Figure 2: Baliatico (Nursing) by Francesco Scaramuzza (275 cm × 214 cm, Parma, Complesso Museale della Pilott...
Figure 3: Schiff’s fictitious report on the foundation of the Gazzetta Chimica Italiana (Image reproduced fro...
Scheme 2: Reaction of thymol (3) with chloroform under the basic conditions of the Guareschi–Lustgarten react...
Figure 4: The chemistry building of Turin University in a historical picture. Note, that one of the “mysterio...
Scheme 3: Triacetonamine (6) and the related compounds phorone (7), α-eucaine (8), and tropinone (9).
Scheme 4: Taxonomy of the Guareschi pyridone syntheses.
Scheme 5: The catalytic cycle of the “1897 reaction”.
Scheme 6: Resonance forms of the radical 10.
Figure 5: The wet chamber used by Guareschi to restore parchments (Gorrini, G. L'incendio della R. Biblioteca...
Figure 6: The Guareschi mask. (Servizio Chimico Militare. L'opera di Icilio Guareschi precursore della masche...
Figure 7: Guareschi’s bust at the Dipartimento di Scienza e Tecnologia del Farmaco of Turin University. Permi...
A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries
- Guido Gambacorta,
- James S. Sharley and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
- less active than the primary amine. The authors suggest the reaction occurs through an imine/iminium intermediate as they confirmed a first order relationship between the reaction rate and the catalyst concentration. After washing with nitromethane, the catalyst could be reused a second time, obtaining
- silica are suggested to play a key role in the water elimination step. Furthermore, the primary amine function on the silica shows better outcomes compared to a tertiary amine. Different products were prepared in moderate to excellent yields, however, with the less acidic diethyl malonate the catalyst
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles
- Joseane A. Mendes,
- Paulo R. R. Costa,
- Miguel Yus,
- Francisco Foubelo and
- Camilla D. Buarque
Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86
- ][9][10][11] and other compounds that show different types of biological activities [12][13]. The way to achieve these transformations is by intramolecular cyclizations, involving the free primary amine, and appropriate reactive positions (those positions bearing a leaving group) in the electrophile
Graphical Abstract
Scheme 1: General strategy for the enantioselective synthesis of N-containing heterocycles from N-tert-butane...
Scheme 2: Methodologies for condensation of aldehydes and ketones with tert-butanesulfinamides (1).
Scheme 3: Transition models for cis-aziridines and trans-aziridines.
Scheme 4: Mechanism for the reduction of N-tert-butanesulfinyl imines.
Scheme 5: Transition models for the addition of organomagnesium and organolithium compounds to N-tert-butanes...
Scheme 6: Synthesis of 2,2-dibromoaziridines 15 from aldimines 14 and bromoform, and proposed non-chelation-c...
Scheme 7: Diastereoselective synthesis of aziridines from tert-butanesulfinyl imines.
Scheme 8: Synthesis of vinylaziridines 22 from aldimines 14 and 1,3-dibromopropene 23, and proposed chelation...
Scheme 9: Synthesis of vinylaziridines 27 from aldimines 14 and α-bromoesters 26, and proposed transition sta...
Scheme 10: Synthesis of 2-chloroaziridines 28 from aldimines 14 and dichloromethane, and proposed transition s...
Scheme 11: Synthesis of cis-vinylaziridines 30 and 31 from aldimines 14 and bromomethylbutenolide 29.
Scheme 12: Synthesis of 2-chloro-2-aroylaziridines 36 and 32 from aldimines 14, arylnitriles 34, and silyldich...
Scheme 13: Synthesis of trifluoromethylaziridines 39 and proposed transition state of the aziridination.
Scheme 14: Synthesis of aziridines 42 and proposed state transition.
Scheme 15: Synthesis of 1-substituted 2-azaspiro[3.3]heptanes, 1-phenyl-2-azaspiro[3.4]octane and 1-phenyl-2-a...
Scheme 16: Synthesis of 1-substituted 2,6-diazaspiro[3.3]heptanes 48 from chiral imines 14 and 1-Boc-azetidine...
Scheme 17: Synthesis of β-lactams 52 from chiral imines 14 and dimethyl malonate (49).
Scheme 18: Synthesis of spiro-β-lactam 57 from chiral (RS)-N-tert-butanesulfinyl isatin ketimine 53 and ethyl ...
Scheme 19: Synthesis of β-lactam 60, a precursor of (−)-batzelladine D (61) and (−)-13-epi-batzelladine D (62)...
Scheme 20: Rhodium-catalyzed asymmetric synthesis of 3-substituted pyrrolidines 66 from chiral imine (RS)-63 a...
Scheme 21: Asymmetric synthesis of 1,3-disubstituted isoindolines 69 and 70 from chiral imine 67.
Scheme 22: Asymmetric synthesis of cis-2,5-disubstituted pyrrolidines 73 from chiral imine (RS)-71.
Scheme 23: Asymmetric synthesis of 3-hydroxy-5-substituted pyrrolidin-2-ones 77 from chiral imine (RS)-74.
Scheme 24: Asymmetric synthesis of 4-hydroxy-5-substituted pyrrolidin-2-ones 80 from chiral imines 79.
Scheme 25: Asymmetric synthesis of 3-pyrrolines 82 from chiral imines 14 and ethyl 4-bromocrotonate (81).
Scheme 26: Asymmetric synthesis of γ-amino esters 84, and tetramic acid derivative 86 from chiral imines (RS)-...
Scheme 27: Asymmetric synthesis of α-methylene-γ-butyrolactams 90 from chiral imines (Z,SS)-87 and ethyl 2-bro...
Scheme 28: Asymmetric synthesis of methylenepyrrolidines 92 from chiral imines (RS)-14 and 2-(trimethysilylmet...
Scheme 29: Synthesis of dibenzoazaspirodecanes from cyclic N-tert-butanesulfinyl imines.
Scheme 30: Stereoselective synthesis of cyclopenta[c]proline derivatives 103 from β,γ-unsaturated α-amino acid...
Scheme 31: Stereoselective synthesis of alkaloids (−)-angustureine (107) and (−)-cuspareine (108).
Scheme 32: Stereoselective synthesis of alkaloids (−)-pelletierine (112) and (+)-coniine (117).
Scheme 33: Synthesis of piperidine alkaloids (+)-dihydropinidine (122a), (+)-isosolenopsin (122b) and (+)-isos...
Scheme 34: Stereoselective synthesis of the alkaloids(+)-sedamine (125) from chiral imine (SS)-119.
Scheme 35: Stereoselective synthesis of trans-5-hydroxy-6-substituted-2-piperidinones 127 and 129 from chiral ...
Scheme 36: Stereoselective synthesis of trans-5-hydroxy-6-substituted ethanone-2-piperidinones 132 from chiral...
Scheme 37: Stereoselective synthesis of trans-3-benzyl-5-hydroxy-6-substituted-2-piperidinones 136 from chiral...
Scheme 38: Stereoselective synthesis of trans-5-hydroxy-6-substituted 2-piperidinones 139 from chiral imine 138...
Scheme 39: Stereoselective synthesis of ʟ-hydroxypipecolic acid 145 from chiral imine 144.
Scheme 40: Synthesis of 1-substituted isoquinolones 147, 149 and 151.
Scheme 41: Stereoselective synthesis of 3-substituted dihydrobenzo[de]isoquinolinones 154.
Scheme 42: Enantioselective synthesis of alkaloids (S)-1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (...
Scheme 43: Enantioselective synthesis of alkaloids (−)-cermizine B (171) and (+)-serratezomine E (172) develop...
Scheme 44: Stereoselective synthesis of (+)-isosolepnosin (177) and (+)-solepnosin (178) from homoallylamine d...
Scheme 45: Stereoselective synthesis of tetrahydroquinoline derivatives 184, 185 and 187 from chiral imines (RS...
Scheme 46: Stereoselective synthesis of pyridobenzofuran and pyridoindole derivatives 193 from homopropargylam...
Scheme 47: Stereoselective synthesis of 2-substituted 1,2,5,6-tetrahydropyridines 196 from chiral imines (RS)-...
Scheme 48: Stereoselective synthesis of 2-substituted trans-2,6-disubstituted piperidine 199 from chiral imine...
Scheme 49: Stereoselective synthesis of cis-2,6-disubstituted piperidines 200, and alkaloid (+)-241D, from chi...
Scheme 50: Stereoselective synthesis of 6-substituted piperidines-2,5-diones 206 and 1,7-diazaspiro[4.5]decane...
Scheme 51: Stereoselective synthesis of spirocyclic oxindoles 210 from chiral imines (RS)-53.
Scheme 52: Stereoselective synthesis of azaspiro compound 213 from chiral imine 211.
Scheme 53: Stereoselective synthesis of tetrahydroisoquinoline derivatives from chiral imines (RS)-214.
Scheme 54: Stereoselective synthesis of (−)-crispine A 223 from chiral imine (RS)-214.
Scheme 55: Synthesis of (−)-harmicine (228) using tert-butanesulfinamide through haloamide cyclization.
Scheme 56: Stereoselective synthesis of tetraponerines T1–T8.
Scheme 57: Stereoselective synthesis of phenanthroindolizidines 246a and (−)-tylophorine (246b), and phenanthr...
Scheme 58: Stereoselective synthesis of indoline, tetrahydroquinoline and tetrahydrobenzazepine derivatives 253...
Scheme 59: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldimine (RS)-79.
Scheme 60: Stereoselective synthesis of (−)-epiquinamide (266) from chiral aldimine (SS)-261.
Scheme 61: Synthesis synthesis of (–)-hippodamine (273) and (+)-epi-hippodamine (272) using chiral sulfinyl am...
Scheme 62: Stereoselective synthesis of (+)-grandisine D (279) and (+)-amabiline (283).
Scheme 63: Stereoselective synthesis of (−)-epiquinamide (266) and (+)-swaisonine (291) from aldimine (SS)-126....
Scheme 64: Stereoselective synthesis of (+)-C(9a)-epi-epiquinamide (294).
Scheme 65: Stereoselective synthesis of (+)-lasubine II (298) from chiral aldimine (SS)-109.
Scheme 66: Stereoselective synthesis of (−)-epimyrtine (300a) and (−)-lasubine II (ent-302) from β-amino keton...
Scheme 67: Stereoselective synthesis of (−)-tabersonine (310), (−)-vincadifformine (311), and (−)-aspidospermi...
Scheme 68: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldehyde 313 and ...
Scheme 69: Total synthesis of (+)-lysergic acid (323) from N-tert-butanesulfinamide (RS)-1.
