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Search for "reagent" in Full Text gives 1289 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
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
- the alcoholate reacted with 1-iodohexadecane to produce 3.3 in 50% yield. The phosphocholine moiety was incorporated by using 2-bromoethyl dichlorophosphate as a key reagent and following a previously reported sequence [67]. The debenzylation by using hydrogenolysis conditions produced 3.5 in 75% to
- method was developed for the incorporation of the phosphocholine polar head group that makes use of the phosphoramidite 8.2 which is a weakly air sensitive reagent [85]. This method was applied for the synthesis of PAF as illustrated in Figure 8 [86]. The alcohol 8.1 reacted with 8.2 in the presence of
- incorporation of a phenyl group between the glycerol and the lipid chain. The lipid chain was bonded to the aromatic ring in either ortho-, meta-, and para-position [91]. The incorporation of a phenyl moiety starts with the reaction of the Grignard reagent formed from 4-bromoanisole (10.1, the other isomers 2
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...
Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates
- Olfa Mhasni,
- Jalloul Bouajila and
- Farhat Rezgui
Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93
- 5a [27] as the model substrate bearing a good leaving group, with imidazole (2a, 2 equiv) as a powerful nucleophilic reagent. The reaction was achieved with no need of a catalyst or any additive in toluene at reflux affording within 24 h the SN2-type product 6a in 82% yield (Table 1, entry 1
Graphical Abstract
Figure 1: Medicines containing an imidazole nucleus.
Scheme 1: Synthesis of N-substituted imidazole derivatives from MBH adducts.
Scheme 2: Proposed mechanism for the allylation of imidazole with alcohol 4a.
Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal
- Alessandro Brusa,
- Debora Iapadre,
- Maria Edith Casacchia,
- Alessio Carioscia,
- Giuliana Giorgianni,
- Giandomenico Magagnano,
- Fabio Pesciaioli and
- Armando Carlone
Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92
- as a reagent has always been challenging. The low boiling point and high volatility pose a problem with its handling and safety. The small steric hindrance gives rise to a high reactivity both as an electrophile and as a pro-nucleophile, hampering chemoselectivity (further to side reactions such as
- nitroalkene derivatives with low reagent excess and high enantioselectivity; this reaction represents the first step in the Enders triple cascade catalytic cycle. The use of acetaldehyde in a two-component cascade reaction was previously reported by Enders [27]; however, the scope of this reaction is limited
Graphical Abstract
Scheme 1: Original triple organocatalytic cascade reaction developed by Enders.
Figure 1: Approaches based on the original Enders cascade reaction to access trisubstituted cyclohexene carba...
Scheme 2: Acetaldehyde dimethyl acetal (6) as an acetaldehyde surrogate to effect a triple organocatalytic ca...
Figure 2: Scope of the cascade reaction using 6 as an acetaldehyde equivalent. Reaction conditions: 3 (0.5 mm...
Radical ligand transfer: a general strategy for radical functionalization
- David T. Nemoto Jr,
- Kang-Jie Bian,
- Shih-Chieh Kao and
- Julian G. West
Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90
- paradigm with photocatalytic ATRA to enable the modular difunctionalization of alkenes under reagent control (Scheme 3). In Stephenson’s photocatalytic ATRA reports, the C–X bond in the product was proposed to be formed through both direct quenching of a transient alkyl radical by halogen atom transfer
- (XAT) from the alkyl halide reagent and further oxidation of the transient radical to a carbocation by radical polar crossover (RPC), providing two mechanistic pathways to form the ATRA products [32]. While powerful, this approach is inherently incompatible with introducing alternative functionality
- instead of the halide included in the alkyl halide reagent, limiting the ability to form different difunctionalization products. Taking inspiration from Groves’ bio-inspired manganese tetradentate manganese catalysts, we found we could instead functionalize the transient alkyl radical via RLT from a
Graphical Abstract
Scheme 1: Overview of the RLT mechanism in nature and in literature. I: The radical rebound mechanism in cyto...
Scheme 2: Areas of recent work on RLT development and application in catalysis. I: Reported RLT pathways ofte...
Scheme 3: The incorporation of RLT catalysis in ATRA photocatalysis. I: The reported method is compatible wit...
Scheme 4: Pioneering and recent work on decarboxylative functionalization involving a posited RLT pathway. I:...
Scheme 5: Our lab reported decarboxylative azidation of aliphatic and benzylic acids. I: The reaction proceed...
Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control
- Carlee A. Montgomery and
- Graham K. Murphy
Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86
- selection of hypervalent iodine compounds have also been assessed in silico to determine the strengths of their σ-holes (Figure 3). Togni’s CF3-benziodoxole reagent (I-5, 0.029 e) possessed the weakest σ-hole from among those analyzed, consistent with monovalent iodobenzene (I-2) [72]. Difluoroiodobenzene
- appreciation and understanding of σ-holes in iodonium ylides, many examples exist where inter- or intramolecular halogen bonding has been invoked to provide a meaningful explanation of unexpected reactivity, of reagent stability, or as a reaction control element. Examples of these include spontaneous
Graphical Abstract
Figure 1: Generic representation of halogen bonding.
Figure 2: Quantitative evaluation of σ-holes in monovalent iodine-containing compounds; and, qualitative mole...
Figure 3: Quantitative evaluation of σ-holes in hypervalent iodine-containing molecules; and, qualitative MEP...
Figure 4: Quantitative evaluation of σ-holes in iodonium ylides; and, qualitative MEP map of I-12 from −0.083...
Scheme 1: Outline of possible reaction pathways between iodonium ylides and Lewis basic nucleophiles (top); a...
Scheme 2: Metal-free cyclopropanations of iodonium ylides, either as intermolecular (a) or intramolecular pro...
Figure 5: Zwitterionic mechanism for intramolecular cyclopropanation of iodonium ylides (left); and, stepwise...
Scheme 3: Metal-free intramolecular cyclopropanation of iodonium ylides.
Figure 6: Concerted cycloaddition pathway for the metal-free, intramolecular cyclopropanation of iodonium yli...
Scheme 4: Reaction of ylide 6 with diphenylketene to form lactone 24 and 25.
Figure 7: Nucleophilic (top) and electrophilic (bottom) addition pathways proposed by Koser and Hadjiarapoglo...
Scheme 5: Indoline synthesis from acyclic iodonium ylide 31 and tertiary amines.
Scheme 6: N-Heterocycle synthesis from acyclic iodonium ylide 31 and secondary amines.
Figure 8: Proposed mechanism for the formation of 33a from iodonium ylides and amines, involving an initial h...
Scheme 7: Indoline synthesis from acyclic iodonium ylides 39 and tertiary amines under blue light photocataly...
Scheme 8: Metal-free cycloproponation of iodonium ylides under blue LED irradiation. aUsing trans-β-methylsty...
Figure 9: Proposed mechanism of the cyclopropanation between iodonium ylides and alkenes under blue LED irrad...
Scheme 9: Formal C–H alkylation of iodonium ylides by nucleophilic heterocycles under blue LED irradiation.
Figure 10: Proposed mechanism of the formal C–H insertion of pyrrole under blue LED irradiation.
Scheme 10: X–H insertions between iodonium ylides and carboxylic acids, phenols and thiophenols.
Figure 11: Mechanistic proposal for the X–H insertion reactions of iodonium ylides.
Scheme 11: Radiofluorination of biphenyl using iodonium ylides 54a–e derived from various β-dicarbonyl auxilia...
Scheme 12: Radiofluorination of arenes using spirocycle-derived iodonium ylides 56.
Scheme 13: Radiofluorination of arenes using SPIAd-derived iodonium ylides 58.
Figure 12: Calculated reaction coordinate for the radiofluorination of iodonium ylide 60.
Scheme 14: Radiofluorination of iodonium ylides possessing various ortho- and para-substituents on the iodoare...
Figure 13: Difference in Gibbs activation energy for ortho- or para-anisyl derived iodonium ylides 63a and 63b....
Figure 14: Proposed equilibration of intermediates to transit between 64a (the initial adduct formed between 6...
Scheme 15: Comparison of 31 and ortho-methoxy iodonium ylide 39 in rhodium-catalyzed cyclopropanation and cycl...
Figure 15: X-ray crystal structure of dimeric 39 [6], (CCDC# 893474) [143,144].
Scheme 16: Enaminone synthesis using diazonium and iodonium ylides.
Figure 16: Transition state calculations for enaminone synthesis from iodonium ylides and thioamides.
Scheme 17: The reaction between ylides 73a–f and N-methylpyrrole under 365 nm UV irradiation.
Figure 17: Crystal structures of 76c (top) and 76e (bottom) [101], (CCDC# 2104180 & 2104181) [143,144].
Photoredox catalysis harvesting multiple photon or electrochemical energies
- Mattia Lepori,
- Simon Schmid and
- Joshua P. Barham
Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81
- products (e.g., 7) whereas irradiation with blue light (λ = 455 nm) provided disubstituted products 8 (Figure 5A). Additionally, adding a different trapping reagent before switching from green to blue light allows for a sequential and controlled substitution in a one-pot reaction (Figure 5B). 2,4,6
- the single electron reduction of aryl halides while simultaneously generating S4•−. Upon C(sp2)–X bond cleavage, an aryl radical is formed and trapped by a trapping reagent such as N-methylpyrrole, yielding the open-shell species 4•. Upon irradiation of S3•−, the excited species *[S3•−] oxidizes 4• to
Graphical Abstract
Figure 1: Oxidative and reductive activations of organic compounds harvesting photoredox catalysis.
Figure 2: General catalytic cycles of radical ion conPET (left) and radical ion e-PRC (right).
Figure 3: “Beginner’s guide”: comparison between advantages, capacities, and prospectives of conPET and PEC.
Figure 4: A) conPET reductive dehalogenation of aryl halides with PDI. B) Reductive C–H arylation with pyrrol...
Figure 5: A) Chromoselective mono- and disubstitution or polybrominated pyrimidines with pyrroles. B) Sequent...
Figure 6: A) Synthesis of pyrrolo[1,2-a]quinolines. B) Synthesis of ullazines.
Figure 7: A) Reductive phosphorylation of aryl halides via conPET. B) Selected examples from the substrate sc...
Figure 8: A) Reductive dehalogenation of aryl halides via conPET and selected examples from the substrate sco...
Figure 9: A) Reductive C–H arylation of aryl halides via conPET (top) and selected examples from the substrat...
Figure 10: A) Reductive hydrodehalogenation of aryl halides with Mes-Acr-BF4. B) Selected examples from the su...
Figure 11: A) Reductive hydrodechlorination of aryl chlorides with 4-DPAIPN. B) Proposed formation of CO2•−. C...
Figure 12: A) Reductive conPET borylation with 3CzEPAIPN (top) and selected examples from the substrate scope ...
Figure 13: Scale-up of conPET phosphorylation with 3CzEPAIPN.
Figure 14: A) Borylation of 1d. B) Characteristics and structure of PC1 with green and red parts showing the l...
Figure 15: A) Reductive C–H arylation scope with polysulfide conPET (top) and selected examples from the subst...
Figure 16: Scale-up of A) C–H arylation and B) dehaloborylation with polysulfide photocatalysis in continuous-...
Figure 17: A) Formation of [Ir1]0 and [Ir2]0 upon PET between [Ir1]+ and Et3N. B) Mechanism of multi-photon ta...
Figure 18: A) Reductive hydrodehalogenation of aryl halides via multi-photon tandem photocatalysis. B) Selecte...
Figure 19: A) Carbonylative amidation of aryl halides in continuous flow. B) Selected examples from the substr...
Figure 20: A) General scheme for reductive (RQ) and oxidative quenching (OQ) protocols using [FeIII(btz)3](PF6)...
Figure 21: A) Carbonylative amidation of alkyl iodides with [IrIII(ppy)2(dtbbpy)]PF6. B) Selected examples fro...
Figure 22: A) Carboxylative C–N bond cleavage in cyclic amines. B) Selected examples from the substrate scope....
Figure 23: A) Formal reduction of alkenes to alkanes via transfer hydrogenation. B) Selected examples from the...
Figure 24: A) Birch-type reduction of benzenes with PMP-BPI. B) Selected examples from the substrate scope (sc...
Figure 25: Proposed mechanism of the OH− mediated conPET Birch-type reduction of benzene via generation of sol...
Figure 26: Reductive detosylation of N-tosylated amides with Mes-Acr-BF4. B) Selected examples from the substr...
Figure 27: A) Reductive detosylation of N-tosyl amides by dual PRC. B) Selected examples from the substrate sc...
Figure 28: A) Mechanism of the dual PRC based on PET between [Cu(dap)2]+ and DCA. B) Mechanism of the dual PRC...
Figure 29: A) N–O bond cleavage in Weinreb amides with anthracene. B) N–O bond cleavage in Weinreb amides rely...
Figure 30: A) Pentafluorosulfanylation and fluoride elimination. B) Mechanism of the pentafluorosulfanylation ...
Figure 31: A) α-Alkoxypentafluorosulfanylation (top) and selected examples from the substrate scope (bottom). ...
Figure 32: A) Oxidative amination of arenes with azoles catalyzed by N-Ph PTZ. B) Selected examples from the s...
Figure 33: A) C(sp3)–H bond activation by HAT via chloride oxidation by *N-Ph PTZ•+. B) Proposed mechanism for...
Figure 34: A) Recycling e-PRC C–H azolation of electron-rich arenes with pyrazoles using Mes-Acr+ as a photoca...
Figure 35: A) Radical ion e-PRC direct oxidation of unactivated arenes using TAC+ as an electro-activated phot...
Figure 36: A) Radical ion e-PRC direct oxidation of unactivated arenes using TPA as an electro-activated photo...
Figure 37: Proposed mechanism (top) and mode of preassembly (bottom).
Figure 38: A) Possible preassemblies of reactive (left) vs unreactive (right) arenes. B) Calculated spin densi...
Figure 39: A) Recycling e-PRC C(sp2 )–H acetoxylation of arenes using DDQ as a photocatalyst. B) Proposed cata...
Figure 40: Gram scale hydroxylation of benzene in a recirculated flow setup.
Figure 41: A) Radical ion e-PRC vicinal diamination of alkylarenes using TAC+ as an electro-activated photocat...
Figure 42: A) Sequential oxygenation of multiple adjacent C–H bonds under radical ion e-PRC using TAC+ as an e...
Figure 43: A) Enantioselective recycling e-PRC cyanation of benzylic C–H bonds using ADQS as photocatalyst. B)...
Figure 44: Proposed tandem mechanism by Xu and co-workers.
Figure 45: A) Enantioselective recycling e-PRC decarboxylative cyanation using Cu(acac)2, Ce(OTf)3 and a box l...
Figure 46: A) Enantioselective recycling e-PRC benzylic cyanation using Cu(MeCN)4BF4, box ligand and anthraqui...
Figure 47: A) Radical ion e-PRC acetoxyhydroxylation of aryl olefins using TAC+ as an electro-activated photoc...
Figure 48: Selected examples from the substrate scope.
Figure 49: Photoelectrochemical acetoxyhydroxylation in a recirculated flow setup.
Figure 50: A) Radical ion e-PRC aminooxygenation of aryl olefins using TAC+ as an electro-activated photocatal...
Figure 51: A) Recycling e-PRC C–H alkylation of heteroarenes with organic trifluoroborates using Mes-Acr+ as p...
Figure 52: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using CeCl3·7H2O as catalyst. B) ...
Figure 53: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using Fe(NH4)2(SO4)2·6H2O as cata...
Figure 54: A) Recycling e-PRC C–H alkylation of heteroarenes with alkyl oxalates and 4CzIPN as photocatalyst. ...
Figure 55: A) Recycling e-PRC decarboxylative C–H carbamoylation of heteroarenes using 4CzIPN as photocatalyst...
Figure 56: A) Photoelectrochemical HAT-mediated hydrocarbon activation via the chlorine radical. B) Proposed m...
Figure 57: A) Selected examples from the substrate scope. B) Gram and decagram scale semi-continuous flow PEC ...
Figure 58: A) Photoelectrochemical HAT-mediated dehydrogenative coupling of benzothiazoles with aliphatic C–H ...
Figure 59: A) Photoelectrochemical HAT activation of ethers using electro-activated TAC+ as photocatalyst. B) ...
Figure 60: Selected examples from the substrate scope.
Figure 61: A) Photoelectrochemical HAT-mediated synthesis of alkylated benzimidazo-fused isoquinolinones using...
Figure 62: A) Decoupled photoelectrochemical cerium-catalyzed oxydichlorination of alkynes using CeCl3 as cata...
Figure 63: Proposed decoupled photoelectrochemical mechanism.
Figure 64: A) Decoupled photoelectrochemical ring-opening bromination of tertiary cycloalkanols using MgBr2 as...
Figure 65: A) Recycling e-PRC ring-opening functionalization of cycloalkanols using CeCl3 as catalyst. B) Prop...
Figure 66: Selected examples from the substrate scope of the PEC ring-opening functionalization.
Figure 67: A) Radical ion e-PRC reduction of chloro- and bromoarenes using DCA as catalyst and various accepto...
Figure 68: A) Screening of different phthalimide derivatives as catalyst for the e-PRC reduction of aryl halid...
Figure 69: Screening of different organic catalysts for the e-PRC reduction of trialkylanilium salts.
Figure 70: A) e-PRC reduction of phosphonated phenols and anilinium salts. B) Selected examples from the subst...
Figure 71: A) ConPET and e-PRC reduction of 4-bromobenzonitrile using a naphthalene diimide (NDI) precatalyst ...
Figure 72: A) Radical ion e-PRC reduction of phosphinated aliphatic alcohols with n-BuO-NpMI as catalyst. B) C...
Figure 73: Selected examples from the substrate scope.
Figure 74: A) Recycling e-PRC reductive dimerization of benzylic chlorides using a [Cu2] catalyst. B) Proposed...
Figure 75: A) Decoupled photoelectrochemical C–H alkylation of heteroarenes through deamination of Katritzky s...
Figure 76: Proposed mechanism by Chen and co-workers.
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
- categorized into two major divisions: 1) covalent bonding and 2) noncovalent bonding catalysts. A covalent bonding organocatalyst reacts with a substrate to form an activated chiral intermediate which undergoes a stereoselective reaction with another reagent. A noncovalent bonding catalyst usually assembles
- formation of a new C–C bond [21]. The reaction requires an electrophilic reagent/intermediate present in the reaction system on which an electrophilic attack by the π-electron cloud of the aromatic ring can occur spontaneously to form a dearomatized species. The latter is rearomatized in a succeeding step
- 2004. In this methodology, a 1,1’-bi-2-naphthol (BINOL)-derived chiral phosphoric acid P1 was used as the catalytic reagent to couple 2-methoxyfuran (1) and N-Boc-protected aldimines 2 to incorporate an aza-tertiary stereocenter into the 2’ position of the heteroaromatic products 3 (Scheme 1) [24
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.
Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors
- Brigita Mudráková,
- Renata Marcia de Figueiredo,
- Jean-Marc Campagne and
- Radovan Šebesta
Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65
- min. Subsequently, 1.2 M dimethylzinc reagent in toluene (0.31 mL, 0.38 mmol, 1.5 equiv) was added dropwise to the solution and the resulting mixture was also stirred for 10 min. The acylimidazole (0.25 mmol, 1.0 equiv) dissolved in anhydrous THF (0.5 mL) was added dropwise to the mixture. The
Graphical Abstract
Scheme 1: Concept of this work.
Scheme 2: Initial experiments for the trapping of the intermediate enolate Enl-1a with tropylium NTf2.
Scheme 3: The reaction scope.
Figure 1: Comparison of DFT-calculated and experimental ECD of (2R,3R)-4 and (2S,3R)-4.
Figure 2: DFT calculated (ωB97X-D4/def2-TZVPPD//PBEh-3c/def2-mSVP) HOMO energies and NBO charges for represen...
Pyridine C(sp2)–H bond functionalization under transition-metal and rare earth metal catalysis
- Haritha Sindhe,
- Malladi Mounika Reddy,
- Karthikeyan Rajkumar,
- Akshay Kamble,
- Amardeep Singh,
- Anand Kumar and
- Satyasheel Sharma
Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62
- yields (Scheme 28). In this reaction, Grignard reagent 148 was used as arylation source in excess amount as the reagent underwent homocoupling leading to the formation of biaryl systems under the reaction conditions. 1,2-Dichloro-2-methylpropane (149) was found to be an effective oxidant under the
Graphical Abstract
Figure 1: Representative examples of bioactive natural products and FDA-approved drugs containing a pyridine ...
Scheme 1: Classical and traditional methods for the synthesis of functionalized pyridines.
Scheme 2: Rare earth metal (Ln)-catalyzed pyridine C–H alkylation.
Scheme 3: Pd-catalyzed C–H alkylation of pyridine N-oxide.
Scheme 4: CuI-catalyzed C–H alkylation of N-iminopyridinium ylides with tosylhydrazones (A) and a plausible r...
Scheme 5: Zirconium complex-catalyzed pyridine C–H alkylation.
Scheme 6: Rare earth metal-catalyzed pyridine C–H alkylation with nonpolar unsaturated substrates.
Scheme 7: Heterobimetallic Rh–Al complex-catalyzed ortho-C–H monoalkylation of pyridines.
Scheme 8: Mono(phosphinoamido)-rare earth complex-catalyzed pyridine C–H alkylation.
Scheme 9: Rhodium-catalyzed pyridine C–H alkylation with acrylates and acrylamides.
Scheme 10: Ni–Al bimetallic system-catalyzed pyridine C–H alkylation.
Scheme 11: Iridium-catalyzed pyridine C–H alkylation.
Scheme 12: para-C(sp2)–H Alkylation of pyridines with alkenes.
Scheme 13: Enantioselective pyridine C–H alkylation.
Scheme 14: Pd-catalyzed C2-olefination of pyridines.
Scheme 15: Ru-catalyzed C-6 (C-2)-propenylation of 2-arylated pyridines.
Scheme 16: C–H addition of allenes to pyridines catalyzed by half-sandwich Sc metal complex.
Scheme 17: Pd-catalyzed stereodivergent synthesis of alkenylated pyridines.
Scheme 18: Pd-catalyzed ligand-promoted selective C3-olefination of pyridines.
Scheme 19: Mono-N-protected amino acids in Pd-catalyzed C3-alkenylation of pyridines.
Scheme 20: Amide-directed and rhodium-catalyzed C3-alkenylation of pyridines.
Scheme 21: Bimetallic Ni–Al-catalyzed para-selective alkenylation of pyridine.
Scheme 22: Arylboronic ester-assisted pyridine direct C–H arylation.
Scheme 23: Pd-catalyzed C–H arylation/benzylation with toluene.
Scheme 24: Pd-catalyzed pyridine C–H arylation with potassium aryl- and heteroaryltrifluoroborates.
Scheme 25: Transient activator strategy in pyridine C–H biarylation.
Scheme 26: Ligand-promoted C3-arylation of pyridine.
Scheme 27: Pd-catalyzed arylation of nicotinic and isonicotinic acids.
Scheme 28: Iron-catalyzed and imine-directed C–H arylation of pyridines.
Scheme 29: Pd–(bipy-6-OH) cooperative system-mediated direct pyridine C3-arylation.
Scheme 30: Pd-catalyzed pyridine N-oxide C–H arylation with heteroarylcarboxylic acids.
Scheme 31: Pd-catalyzed C–H cross-coupling of pyridine N-oxides with five-membered heterocycles.
Scheme 32: Cu-catalyzed dehydrative biaryl coupling of azine(pyridine) N-oxides and oxazoles.
Scheme 33: Rh(III)-catalyzed cross dehydrogenative C3-heteroarylation of pyridines.
Scheme 34: Pd-catalyzed C3-selective arylation of pyridines.
Scheme 35: Rhodium-catalyzed oxidative C–H annulation of pyridines to quinolines.
Scheme 36: Rhodium-catalyzed and NHC-directed C–H annulation of pyridine.
Scheme 37: Ni/NHC-catalyzed regio- and enantioselective C–H cyclization of pyridines.
Scheme 38: Rare earth metal-catalyzed intramolecular C–H cyclization of pyridine to azaindolines.
Scheme 39: Rh-catalyzed alkenylation of bipyridine with terminal silylacetylenes.
Scheme 40: Rollover cyclometallation in Rh-catalyzed pyridine C–H functionalization.
Scheme 41: Rollover pathway in Rh-catalyzed C–H functionalization of N,N,N-tridentate chelating compounds.
Scheme 42: Pd-catalyzed rollover pathway in bipyridine-6-carboxamides C–H arylation.
Scheme 43: Rh-catalyzed C3-acylmethylation of bipyridine-6-carboxamides with sulfoxonium ylides.
Scheme 44: Rh-catalyzed C–H functionalization of bipyridines with alkynes.
Scheme 45: Rh-catalyzed C–H acylmethylation and annulation of bipyridine with sulfoxonium ylides.
Scheme 46: Iridium-catalyzed C4-borylation of pyridines.
Scheme 47: C3-Borylation of pyridines.
Scheme 48: Pd-catalyzed regioselective synthesis of silylated dihydropyridines.
Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones
- Ksenia Malkova,
- Andrey Bubyrev,
- Stanislav Kalinin and
- Dmitry Dar’in
Beilstein J. Org. Chem. 2023, 19, 800–807, doi:10.3762/bjoc.19.60
- of the secondary quinoline-3-sulfonamide synthesis, the increase of reagent excesses in relation to ketosulfonamide resulted in the conversion and an increase of the yield as observed by TLC (see GP2 in Supporting Information File 1). Chromatographic purification afforded compounds 5a–q mostly in
- target products (Scheme 3, 5e and 5g). The drop was especially dramatic for the nitro group containing reagent 1f. Indeed, the transformation was accompanied by a number of side reactions according to TLC. To our delight, the protocol turned out to be suitable for α-sulfonyl-substituted alkyl acetates
- carbonyl group deactivation. Furthermore, while implementing the protocol for 2-azidoquinoline-3-carbaldehyde (1t), a low conversion of this reagent was detected, which can be explained by the fact that 1t tends to exist in the inactive tetrazole form. In addition, our attempt to involve Boc-protected
Graphical Abstract
Figure 1: a) Conventional drugs containing either a sulfonamide fragment or a quinoline core; b) biologically...
Figure 2: Knoevenagel condensation/aza-Wittig reaction cascade for the quinoline core formation.
Scheme 1: Key reaction steps during the synthesis of 3-sulfonyl-substituted quinolines.
Scheme 2: Synthetic routes to sulfonamides and sulfones 2 and the set of reagents for the preparation of comp...
Scheme 3: Preparation of 3-sulfonyl substituted quinolines 5a–q.
Scheme 4: 3-Sulfonyl-substituted quinolines 5r–v that failed to be synthesized.
Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment
- Constantine V. Milyutin,
- Andrey N. Komogortsev,
- Boris V. Lichitsky,
- Mikhail E. Minyaev and
- Valeriya G. Melekhina
Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58
- 9a was obtained in 15% yield (Table 1, entry 1). Next, we repeated the above-mentioned reaction under similar conditions without a basic reagent and the exclusion of the base led to a significant increase in the yield of the target product 9a (Table 1, entry 2). Next, we tested the reaction in
- to 2 h did not affect the yield of pyrimidine 9a (Table 1, entry 8). It is important to emphasize that the use of bases essentially impaired the efficiency of the method (Table 1, entries 9 and 10). Apparently, the addition of a basic reagent does not influence the main process and the decrease in
Graphical Abstract
Scheme 1: Photochemical behavior of terarylenes containing an allomaltol fragment.
Scheme 2: Synthesis of starting compounds 9. Reaction conditions: 13 (1 mmol), NH2CN (14, 3 mmol, 0.13 g), Et...
Scheme 3: Proposed mechanism for the formation of compounds 9.
Scheme 4: Synthesis of methylated derivatives 10. Reaction conditions: 9 (1 mmol), MeI (3 mmol, 0.43 g), K2CO3...
Figure 1: 1H NMR monitoring of the photoreaction of compound 10a under UV irradiation (365 nm) in DMSO-d6 sol...
Figure 2: The crystal structure of compound 11a (one of two polymorph modifications; p = 50%), CCDC 2248033.
Scheme 5: Photochemical synthesis of compounds 11 and 12.
Scheme 6: Proposed mechanism for the studied photoreaction.
Scheme 7: Synthesis of compounds 11g–j starting from pyrimidines 9. Reaction conditions: 9 (0.5 mmol), DMF (1...
Figure 3: One of crystallographically unique molecules of 11g (p = 50%), CCDC 2248035.
Scheme 8: Synthesis of photoproducts 12. Reaction conditions: method A) 10 (0.5 mmol), DMF (15 mL) irradiatio...
Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines
- Joydev K. Laha,
- Pankaj Gupta and
- Amitava Hazra
Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57
- persulfate (K2S2O8) as the exclusive reagent [14]. The mechanistic study revealed that an initial oxidation to an iminium ion could be the key intermediate in the intramolecular cyclization step. In sharp contrast, when N-aryl(benzyl)amines that do not have an ortho-substituted nucleophile in aniline ring
Graphical Abstract
Scheme 1: Various synthetic approaches to N-arylsulfonylimines.
Scheme 2: Substrate scope for the synthesis of N-arylsulfonylimines. Reaction conditions: 1a (0.25 mmol), K2S2...
Scheme 3: Tandem “one-pot” synthesis of N-heterocycles. Reaction conditions: 1a (0.25 mmol), K2S2O8 (0.5 mmol...
Scheme 4: Control experiment with TEMPO.
Scheme 5: Plausible mechanism for the K2S2O8-induced oxidation of N-(arylsulfonyl)benzylamines.
Scheme 6: Plausible mechanism for one-pot synthesis of N-heterocycles.
Construction of hexabenzocoronene-based chiral nanographenes
- Ranran Li,
- Di Wang,
- Shengtao Li and
- Peng An
Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54
- compound 12. Meanwhile, Campaña, Morcillo, and co-workers converted the eight-membered ring 11 to nonagon-containing carbohelicene 14 through a single ring expansion reaction by treating 11 with TMSCHN2 (Scheme 2). By reacting with Tebbe’s reagent, compound 14 could be converted to all-carbon analogue 15
- this helical aza-NG was achieved by introducing a chiral auxiliary reagent at the nitrogen site [40], and the racemization barrier of one enantiomer was measured as 26.2 kcal/mol by monitoring the changes of CD spectra at 60–80 °C. The synthesis started with the Diels−Alder reaction of 5H-dibenzo[b,f
Graphical Abstract
Scheme 1: Construction of HBC by Scholl reaction from hexaphenylbenzene.
Scheme 2: Synthesis of seco-HBC-based chiral nanographenes.
Scheme 3: Synthesis of nitrogen-doped, seco-HBC-based chiral nanographenes.
Scheme 4: Synthesis of π-extended [7]- and [9]helicene containing chiral nanographenes.
Scheme 5: Synthesis of “HBC-dimer”-based chiral nanographenes.
Scheme 6: Synthesis of “HBC-dimer”-based chiral nanographenes.
Scheme 7: Synthesis of axis-based chiral nanographenes.
Scheme 8: Synthesis of “HBC-trimers”-based nanoribbons.
Scheme 9: Synthesis of “HBC-trimers”-based, triangle-shaped chiral nanographenes.
Scheme 10: Synthesis of “HBC-trimers”-based, triangle-shaped chiral nanographenes.
Scheme 11: Synthesis of HBC-based multilayer nanographenes.
Scheme 12: Synthesis of a chiral nanographene constructed by “HBC-tetramers”.
Scheme 13: Synthesis of a triskelion-shaped nanographene constructed by four HBCs.
Scheme 14: Synthesis of a three-dimensional nanographene bearing four HBCs.
Scheme 15: Synthesis of a chiral nanographene constructed by five HBC units.
Scheme 16: Synthesis of a chiral nanographene constructed by seven HBC units.
Strategies in the synthesis of dibenzo[b,f]heteropines
- David I. H. Maier,
- Barend C. B. Bezuidenhoudt and
- Charlene Marais
Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51
- underwent intramolecular Ullmann-type coupling catalysed by CuBr·DMS to form the fused dihydro[b,f]oxepine ring system in 89% yield, whereafter hydrogenation afforded 105 in almost quantitative yield (Scheme 22). The method is a sequence of 12 steps, the majority of which are to prepare Wittig reagent
- from 2-bromostyrene (116) via halogen–lithium exchange and quenching with the appropriate heteroatom source (SiR2Cl2, SnMe2Cl2, GeR2Cl2, BBr3). P-Tethered dienes were synthesised via quenching of a 2-vinylphenyl Grignard reagent with phenylphosphonic dichloride (PhPOCl2). O-Tethered dienes were
Graphical Abstract
Figure 1: Dibenzo[b,f]azepine (1a), -oxepine (1b) and -thiepine (1c) as examples of dibenzo[b,f]heteropines (1...
Figure 2: Selected pharmaceuticals with the dibenzo[b,f]azepine skeleton.
Figure 3: Examples of 10,11-dihydrodibenzo[b,f]azepine-based ligands.
Figure 4: The dibenzo[b,f]azepine moiety in dyes with properties suitable for the use in organic light emitti...
Figure 5: Selective bioactive natural products (13–18) containing the dibenzo[b,f]oxepine scaffold and Novart...
Scheme 1: Retrosynthetic approach to 5H-dibenzo[b,f]azepine (1a) from nitrotoluene (22).
Scheme 2: Oxidative coupling of o-nitrotoluene (22) and reduction of 2,2'-dinitrobibenzyl (21) to form 2,2'-d...
Scheme 3: Synthesis of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a) via amine condensation.
Scheme 4: Catalytic reduction of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a).
Scheme 5: The Wagner–Meerwein rearrangement of acridin-9-ylmethanol (23) into 5H-dibenzo[b,f]azepine (1a).
Scheme 6: Oxidative ring expansion of 2-(9-xanthenyl)malonates 24.
Scheme 7: Ring expansion via C–H functionalisation.
Scheme 8: The synthesis of fluorinated 5H-dibenzo[b,f]azepine 38 from isatin (32).
Scheme 9: The synthesis of substituted dibenzo[b,f]azepines 43 from indoles 39.
Scheme 10: Retrosynthetic pathways to dibenzo[b,f]azepines via Buchwald–Hartwig amination.
Scheme 11: Synthesis of dibenzo[b,f]oxepine 54 and -azepine 55 derivatives via (i) Heck reaction and (ii) Buch...
Scheme 12: Double Buchwald–Hartwig amination and thioetherification in the synthesis of tricyclic azepines 60 ...
Scheme 13: Double Buchwald–Hartwig amination towards substituted dibenzoazepines 62.
Scheme 14: Double Buchwald–Hartwig amination towards 10,11-dihydro-5H-dibenzo[b,f]azepine derivatives 71.
Scheme 15: One-pot Suzuki coupling–Buchwald–Hartwig amination.
Scheme 16: One-pot Rh/Pd-catalysed synthesis of dihydropyridobenzazepines.
Scheme 17: A retrosynthetic pathway to dibenzo[b,f]azepines via Mizoroki–Heck reaction.
Scheme 18: One-pot domino Pd-catalyzed Mizoroki–Heck–Buchwald–Hartwig synthesis of dibenzo[b,f]azepines.
Scheme 19: Dibenzo[b,f]thiapine and -oxepine synthesis via SNAr (thio)etherification, Wittig methylenation and...
Scheme 20: A retrosynthetic pathway to dibenzo[b,f]oxepines via Ullmann coupling.
Scheme 21: Ullmann-type coupling in dibenzo[b,f]oxepine synthesis.
Scheme 22: Wittig reaction and Ullmann coupling as key steps in dihydrobenz[b,f]oxepine synthesis.
Scheme 23: Pd-catalysed dibenzo[b,f]azepine synthesis via norbornene azepine intermediate 109.
Scheme 24: A simple representation of olefin metathesis resulting in transalkylidenation.
Scheme 25: Ring-closing metathesis as key step in the synthesis of dibenzo[b,f]heteropines.
Scheme 26: Alkyne–aldehyde metathesis in the synthesis of dibenzo[b,f]heteropines.
Scheme 27: Hydroarylation of 9-(2-alkynylphenyl)-9H-carbazole derivatives.
Scheme 28: Oxidative coupling of bisphonium ylide intermediate to give pacharin (13).
Scheme 29: Preparation of 10,11-dihydrodibenzo[b,f]heteropines via intramolecular Wurtz reaction.
Scheme 30: Phenol deprotonation and intramolecular etherification in the synthesis of bauhinoxepine J.
Figure 6: Functionalisation of dibenzo[b,f]azepine.
Scheme 31: Palladium-catalysed N-arylation of dibenzo[b,f]azepine.
Scheme 32: Cu- and Ni-catalysed N-arylation.
Scheme 33: N-Alkylation of dibenzo[b,f]azepine (1a) and dihydrodibenzo[b,f]azepine (2a).
Scheme 34: Preparation of methoxyiminosilbene.
Scheme 35: Synthesis of oxcarbazepine (153) from methoxy iminostilbene 151.
Scheme 36: Ring functionalisation of dihydrodibenzo[b,f]azepine.
Synthesis of medium and large phostams, phostones, and phostines
- Jiaxi Xu
Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50
- the iodinium agent. However, the corresponding 7-bromomethyl product 50b was not isolated with bromo(biscollidine) hexafluorophosphate as the brominium reagent. The reactants were further extended to functionalized hydrogen methyl 1,3-dioxolane-fused pent-4-en-1-ylphosphonate 51 with bromo
- (biscollidine) hexafluorophosphate as the brominium reagent, leading to the corresponding 3-benzyloxy-6-bromo-1,2-oxaphosphepane 2-oxide 52 in 64% yield. The reaction of hydrogen methyl 1,3-dioxolane-fused hex-5-en-1-ylphosphonate 53 with bromo(biscollidine) hexafluorophosphate produced the corresponding 4
- ) hexafluorophosphate as the reagent, while they generated mixtures of 7-(1-iodoalkylidene)-1,2-oxaphosphepane 2-oxides 60 and 8-alkyl-7-iodo-2-methoxy-3,4,5,6-tetrahydro-1,2-oxaphosphocine 2-oxides 59b with iodo(biscollidine) hexafluorophosphate as the reagent (Scheme 12) [32]. 1.3 Synthesis via P–C bond formation The
Graphical Abstract
Figure 1: Biologically active agents and chiral ligands containing medium and large phostams, phostones, and ...
Figure 2: Synthetic strategies for the preparation of medium and large phostams, phostones, and phostines.
Scheme 1: Synthesis of 1,2-azaphosphepine 2-oxide, 1,2-azaphosphocine 2-oxide, 1,2-azaphosphepane 2-oxide, an...
Scheme 2: Synthesis of bis[1,2]oxaphosphepine 2-oxide from tert-butyl 2-(bis(allyloxy)phosphoryl)pent-4-enoat...
Scheme 3: Synthesis of 2-ethoxy-5H-benzo[f][1,2]oxaphosphepine 2-oxides from 2-allylphenyl ethyl vinylphospho...
Scheme 4: Synthesis of 2-ethoxy-3,6-dihydrobenzo[g][1,2]oxaphosphocine 2-oxides from 2-allylphenyl ethyl ally...
Scheme 5: Synthesis of benzothiophene-fused 2-hydroxy-1,2-oxaphosphecane 2-oxide from (4-allyl-2-(4-methylphe...
Scheme 6: Synthesis of benzothiophene-fused 2-hydroxy-1,2-oxaphosphecane 2-oxide from benzyl hydrogen ((4-all...
Scheme 7: Synthesis of benzothiophene-fused 2-hydroxy-1-oxa-2-phosphacycloundecane 2-oxide from benzyl hydrog...
Scheme 8: Synthesis of 5,6,7-trihydro-1,2-oxaphosphepine 2-oxide and its benzo derivatives from 3-bromobut-3-...
Scheme 9: Synthesis of thieno[2,3-d]pyrimidine-fused 2-hydroxy-1,2-oxaphosphonane 2-oxide from benzyl hydroge...
Scheme 10: Synthesis of 3-phenoxybenzo[f]pyreno[1,10-cd][1,2]oxaphosphepine 3-oxide from diphenyl pyren-1-ylph...
Scheme 11: Synthesis of 1,2-oxaphosphepane 2-oxides and 1,2-oxaphosphocane 2-oxide from hydrogen methyl hex-5-...
Scheme 12: Synthesis of 2-methoxy-1,2-oxaphosphinane 2-oxides, 1,2-oxaphosphepine 2-oxides, 1,2-oxaphosphepane...
Scheme 13: Synthesis of 1,2-azaphosphepane 2-oxide and its benzo derivatives from 5-bromohex-5-en-1-yl methylp...
Scheme 14: Synthesis of 4-phenyl-1,2-dihydronaphtho[2,1-c][1,2]oxaphosphinine 4-oxide and 1-phenyl-3,4-dihydro...
Scheme 15: Synthesis of 2-alkoxy-3,5-dimethylene-1,2-oxaphosphepane 2-oxides from dialkyl 2-bromo-1-methylethy...
Scheme 16: Synthesis of 14-methyl-2-phenoxy-1-oxa-2-phosphacyclotetradecane 2-oxide from phenyl hydrogen (12-h...
Scheme 17: Synthesis of 5-oxo-1,3,5-trihydrobenzo[f][1,2]azaphosphepine 2-oxides from 1,2-dihydro-4H-benzo[d][...
Scheme 18: Synthesis of 3-hydrobenzo[f][1,2]oxaphosphepin-5(4H)-one 2-oxides from 2-phenyl/alkoxy-4H-benzo[d][...
Scheme 19: Synthesis of bicyclic seven- and eight-membered phosphotones from cycloalk-2-enones and dimethyl ph...
Scheme 20: Synthesis of binaphthylene-fused phosphotones from (M)-2'-methyl-[1,1'-binaphthalen]-2-ol and pheny...
Scheme 21: Synthesis of bicyclic phosphotone from (1S,2R)-2-methyl-3-(phenylsulfonyl)cyclohept-3-en-1-ol and d...
Photocatalytic sequential C–H functionalization expediting acetoxymalonylation of imidazo heterocycles
- Deepak Singh,
- Shyamal Pramanik and
- Soumitra Maity
Beilstein J. Org. Chem. 2023, 19, 666–673, doi:10.3762/bjoc.19.48
- from academia and industry. Herein, we report a direct C-3 acetoxymalonylation of imidazo heterocycles using relay C–H functionalization enabled by organophotocatalysis starring zinc acetate in the triple role of an activator, ion scavenger as well as an acetylating reagent. The mechanistic
Graphical Abstract
Scheme 1: Strategies of C-3 functionalizations of IPs and present work.
Scheme 2: Substrate scope. Conditions: unless otherwise noted, all reactions were carried out with 1 (0.2 mmo...
Scheme 3: Mechanistic investigations.
Scheme 4: Plausible reaction mechanism.
Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles
- Ekaterina A. Lystsova,
- Maksim V. Dmitriev,
- Andrey N. Maslivets and
- Ekaterina E. Khramtsova
Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46
- APBTT 1a with methanol (2a) were optimized. The best yield of PBTA 3aa was observed when methanol was used both as a solvent and a reagent and heated at 65 °C for 1 h (entry 7, Table 1). It is useful to note that, under these conditions, an increase in the heating time (up to 6 h) did not affect the
Graphical Abstract
Figure 1: Biologically active PBTAs.
Scheme 1: Approaches to PBTAs via annulation of benzothiazoles.
Scheme 2: Approaches to PBTAs via annulation of o-aminothiophenols.
Scheme 3: Approach to PBTAs via radical substitution reaction in 1-(2-bromophenyl)-5-(butylsulfanyl)pyrrolidi...
Scheme 4: Approach to PBTAs via intramolecular cyclizations of 1-(2-thiophenyl)pyrroles.
Scheme 5: A new approach to PBTAs via nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazin...
Figure 2: Electrophilic centers in FPDs.
Scheme 6: Reaction of APBTT 1a with methanol (2a).
Scheme 7: Derivatization of PBTA 3aa.
Scheme 8: Reaction of APBTTs 1a–h with alcohols 2a–c. Isolated yields are given; reaction scale: a mixture of ...
Scheme 9: Side-reaction of APBTTs 1 with alcohols 2.
Scheme 10: Transformations of compounds 5 in solutions.
Scheme 11: Reaction of APBTT 1a with benzylamine.
Scheme 12: Derivatization of PBTA 7a.
Scheme 13: Reaction of APBTTs 1a–h and benzylamine. Isolated yields are given; reaction scale: a mixture of 1 ...
Scheme 14: Reaction of APBTT 1a with an excess of benzylamine.
Scheme 15: Reaction of APBTT 1a with morpholine.
Scheme 16: Reaction of APBTT 1a with aniline (11a).
Scheme 17: Derivatization of PBTA 12aa.
Scheme 18: Reaction of APBTTs 1a–h and arylamines 11a–d. Isolated yields are given; reaction scale: a mixture ...
Scheme 19: Side-reaction of APBTT 1a with arylamine 11b.
Scheme 20: Reaction of APBTT 1a with compounds 16a–d.
Scheme 21: Formation of compounds 17 as an undesired process during the synthesis of APBTTs 1.
Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles
- Péter Kisszékelyi and
- Radovan Šebesta
Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44
- years of development. The effort of our group to broaden possibilities to engage metal enolates in reactions with new electrophiles is described. The material is divided according to the organometallic reagent employed in the conjugate addition step, and thus to the particular metal enolate formed
- high diastereoselectivity and good to excellent yields. In most cases, the authors detected only a single diastereomer in the crude reaction mixture (NMR). Using the enantiomeric form of the ligand or the chiral sulfoximine reagent, four diastereomeric β-aminoketones can be produced in excellent
- –Jung vinylsilane reagents 33. Kawamura et al. performed zinc enolate trapping reactions using ligand L10, a chiral quinoline-based N,N,P-ligand (Scheme 8A) [35]. The authors have concluded that the strict control of the amount of organozinc reagent added is essential to avoid side-product formation
Graphical Abstract
Scheme 1: General scheme depicting tandem reactions based on an asymmetric conjugate addition followed by an ...
Scheme 2: Cu-catalyzed tandem conjugate addition of R2Zn/aldol reaction with chiral acetals.
Scheme 3: Cu-catalyzed asymmetric desymmetrization of cyclopentene-1,3-diones using a tandem conjugate additi...
Scheme 4: Stereocontrolled assembly of dialkylzincs, cyclic enones, and sulfinylimines utilizing a Cu-catalyz...
Scheme 5: Cu-catalyzed tandem conjugate addition/Mannich reaction (A). Access to chiral isoindolinones and tr...
Scheme 6: Cu-catalyzed tandem conjugate addition/nitro-Mannich reaction (A) with syn–anti or syn–syn selectiv...
Figure 1: Various chiral ligands utilized for the tandem conjugate addition/Michael reaction sequences.
Scheme 7: Cu-catalyzed tandem conjugate addition/Michael reaction: side-product formation with chalcone (A) a...
Scheme 8: Zn enolate trapping using allyl iodides (A), Stork–Jung vinylsilane reagents (B), and allyl bromide...
Scheme 9: Cu-catalyzed tandem conjugate addition/acylation through Li R2Zn enolate (A). A four-component coup...
Scheme 10: Selected examples for the Cu-catalyzed tandem conjugate addition/trifluoromethylthiolation sequence....
Scheme 11: Zn enolates trapped by vinyloxiranes: synthesis of allylic alcohols.
Scheme 12: Stereoselective cyclopropanation of Mg enolates formed by ACA of Grignard reagents to chlorocrotona...
Scheme 13: Domino aldol reactions of Mg enolates formed from coumarin and chromone.
Scheme 14: Oxidative coupling of ACA-produced Mg enolates.
Scheme 15: Tandem ACA of Grignard reagents to enones and Mannich reaction.
Scheme 16: Diastereodivergent Mannich reaction of Mg enolates with differently N-protected imines.
Scheme 17: Tandem Grignard–ACA–Mannich using Taddol-based phosphine-phosphite ligands.
Scheme 18: Tandem reaction of Mg enolates with aminomethylating reagents.
Scheme 19: Tandem reaction composed of Grignard ACA to alkynyl enones.
Scheme 20: Rh/Cu-catalyzed tandem reaction of diazo enoates leading to cyclobutanes.
Scheme 21: Tandem Grignard-ACA of cyclopentenones and alkylation of enolates.
Scheme 22: Tandem ACA of Grignard reagents followed by enolate trapping reaction with onium compounds.
Scheme 23: Mg enolates generated from unsaturated lactones in reaction with activated alkenes.
Scheme 24: Lewis acid mediated ACA to amides and SN2 cyclization of a Br-appended enolate.
Scheme 25: Trapping reactions of aza-enolates with Michael acceptors.
Scheme 26: Si enolates generated by TMSOTf-mediated ACA of Grignard reagents and enolate trapping reaction wit...
Scheme 27: Trapping reactions of enolates generated from alkenyl heterocycles (A) and carboxylic acids (B) wit...
Scheme 28: Reactions of heterocyclic Mg enolates with onium compounds.
Scheme 29: Synthetic transformations of cycloheptatrienyl and benzodithiolyl substituents.
Scheme 30: Aminomethylation of Al enolates generated by ACA of trialkylaluminum reagents.
Scheme 31: Trapping reactions of enolates with activated alkenes.
Scheme 32: Alkynylation of racemic aluminum or magnesium enolates.
Scheme 33: Trapping reactions of Zr enolates generated by Cu-ACA of organozirconium reagents.
Scheme 34: Chloromethylation of Zr enolates using the Vilsmeier–Haack reagent.
Scheme 35: Tandem conjugate borylation with subsequent protonation or enolate trapping by an electrophile.
Scheme 36: Tandem conjugate borylation/aldol reaction of cyclohexenones.
Scheme 37: Selected examples for the tandem asymmetric borylation/intramolecular aldol reaction; synthesis of ...
Scheme 38: Cu-catalyzed tandem methylborylation of α,β-unsaturated phosphine oxide in the presence of (R,Sp)-J...
Scheme 39: Cu-catalyzed tandem transannular conjugated borylation/aldol cyclization of macrocycles containing ...
Scheme 40: Stereoselective tandem conjugate borylation/Mannich cyclization: selected examples (A) and a multi-...
Scheme 41: Some examples of Cu-catalyzed asymmetric tandem borylation/aldol cyclization (A). Application to di...
Scheme 42: Atropisomeric P,N-ligands used in tandem conjugate borylation/aldol cyclization sequence.
Scheme 43: Selected examples for the enantioselective Cu-catalyzed borylation/intramolecular Michael addition ...
Scheme 44: Selected examples for the preparation of enantioenriched spiroindanes using a Cu-catalyzed tandem c...
Scheme 45: Enantioselective conjugate borylation of cyclobutene-1-carboxylic acid diphenylmethyl ester 175 wit...
Scheme 46: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 47: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 48: Cu-catalyzed tandem conjugate silylation/aldol condensation. The diastereoselectivity is controlled...
Scheme 49: Chiral Ru-catalyzed three-component coupling reaction.
Scheme 50: Rh-Phebox complex-catalyzed reductive cyclization and subsequent reaction with Michael acceptors th...
Scheme 51: Rh-catalyzed tandem asymmetric conjugate alkynylation/aldol reaction (A) and subsequent spiro-cycli...
Scheme 52: Rh-bod complex-catalyzed tandem asymmetric conjugate arylation/intramolecular aldol addition (A). S...
Scheme 53: Co-catalyzed C–H-bond activation/asymmetric conjugate addition/aldol reaction.
Scheme 54: (Diisopinocampheyl)borane-promoted 1,4-hydroboration of α,β-unsaturated morpholine carboxamides and...
Figure 2: Some examples of total syntheses that have been recently reviewed.
Scheme 55: Stereoselective synthesis of antimalarial prodrug (+)-artemisinin utilizing a tandem conjugate addi...
Scheme 56: Amphilectane and serrulatane diterpenoids: preparation of chiral starting material via asymmetric t...
Scheme 57: Various asymmetric syntheses of pleuromutilin and related compounds based on a tandem conjugate add...
Scheme 58: Total synthesis of glaucocalyxin A utilizing a tandem conjugate addition/acylation reaction sequenc...
Scheme 59: Installation of the exocyclic double bond using a tandem conjugate addition/aminomethylation sequen...
Scheme 60: Synthesis of the taxol core using a tandem conjugate addition/enolate trapping sequence with Vilsme...
Scheme 61: Synthesis of the tricyclic core of 12-epi-JBIR-23/24 utilizing a Rh-catalyzed asymmetric conjugate ...
Scheme 62: Total synthesis of (−)-peyssonoside A utilizing a Cu-catalyzed enantioselective tandem conjugate ad...
Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme
- Josipa Matić,
- Tana Tandarić,
- Marijana Radić Stojković,
- Filip Šupljika,
- Zrinka Karačić,
- Ana Tomašić Paić,
- Lucija Horvat,
- Robert Vianello and
- Lidija-Marija Tumir
Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40
- with pyrenecarboxylic acid in the presence of triethylamine (TEA), N,N,N’,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uronium hexafluorophosphate (HBTU) as the coupling reagent, and 1-hydroxybenzotriazole (HOBT) as a coupling additive to give the products Phen-Py-1 and Phen-Py-2 (Scheme 2) in 56% and 84
Graphical Abstract
Scheme 1: Novel pyrene–phenanthridine conjugates Phen-Py-1 (longer, flexible linker) and Phen-Py-2 (shorter, ...
Scheme 2: Synthesis of Phen-Py-1 and Phen-Py-2 by amide formation; Reagents and conditions: 1. TFA–H2O mixtur...
Figure 1: 2D (left) and 3D (right) representation of fluorescence emission spectra of Phen-Py-1 (c = 2 × 10−6...
Figure 2: Most representative structures of the conjugates Phen-Py-1 and Phen-Py-2 at different pH conditions...
Figure 3: UV–vis titration of Phen-Py-1 with ct-DNA,; changes in the UV–vis spectra of Phen-Py-1 at λ = 350 n...
Figure 4: . Experimental (■) and calculated (–) (by Scatchard equation Table 2) fluorescence intensities of compound ...
Figure 5: Comparison of spectra of DNA-dye complex (r = 0.5, black) and sum of DNA and dye spectra (red) of a...
Figure 6: Fluorimetric titration of Phen-Py-1, λexc = 352 nm, c = 1 × 10−6 mol dm−3 with dipeptidyl peptidase...
Figure 7: A: ITC titration: raw titration data from the experimental injections of human DPP III enzyme mutan...
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
- -Innovation Center of Efficient Processing and Utilization of Forest Resources College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China 10.3762/bjoc.19.39 Abstract A synthetic route to the bench-stable fluorinated masked carbene reagent diethyl 2-diazo-1,1,3,3,3
- ). 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
- difluoromethylphosphonate groups at the ring might be possible by using our newly developed bench-stable diazo reagent CF3C(N2)CF2P(O)(OEt)2. Therefore, we report herein our preliminary results toward this goal via copper iodide-catalyzed cyclopropanation reaction of an acceptor carbene precursor with selected terminal
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.
Transition-metal-catalyzed domino reactions of strained bicyclic alkenes
- Austin Pounder,
- Eric Neufeld,
- Peter Myler and
- William Tam
Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38
Graphical Abstract
Figure 1: Ring-strain energies of homobicyclic and heterobicyclic alkenes in kcal mol−1. a) [2.2.1]-Bicyclic ...
Figure 2: a) Exo and endo face descriptions of bicyclic alkenes. b) Reactivity comparisons for different β-at...
Scheme 1: Ni-catalyzed ring-opening/cyclization cascade of heterobicyclic alkenes 1 with alkyl propiolates 2 ...
Scheme 2: Ni-catalyzed ring-opening/cyclization cascade of heterobicyclic alkenes 8 with β-iodo-(Z)-propenoat...
Scheme 3: Ni-catalyzed two- and three-component difunctionalizations of norbornene derivatives 15 with alkyne...
Scheme 4: Ni-catalyzed intermolecular three-component difunctionalization of oxabicyclic alkenes 1 with alkyn...
Scheme 5: Ni-catalyzed intermolecular three-component carboacylation of norbornene derivatives 15.
Scheme 6: Photoredox/Ni dual-catalyzed coupling of 4-alkyl-1,4-dihydropyridines 31 with heterobicyclic alkene...
Scheme 7: Photoredox/Ni dual-catalyzed coupling of α-amino radicals with heterobicyclic alkenes 30.
Scheme 8: Cu-catalyzed rearrangement/allylic alkylation of 2,3-diazabicyclo[2.2.1]heptenes 47 with Grignard r...
Scheme 9: Cu-catalyzed aminoboration of bicyclic alkenes 1 with bis(pinacolato)diboron (B2pin2) (53) and O-be...
Scheme 10: Cu-catalyzed borylalkynylation of oxabenzonorbornadiene (30b) with B2pin2 (53) and bromoalkynes 62.
Scheme 11: Cu-catalyzed borylacylation of bicyclic alkenes 1.
Scheme 12: Cu-catalyzed diastereoselective 1,2-difunctionalization of oxabenzonorbornadienes 30 for the synthe...
Scheme 13: Fe-catalyzed carbozincation of heterobicyclic alkenes 1 with arylzinc reagents 74.
Scheme 14: Co-catalyzed addition of arylzinc reagents of norbornene derivatives 15.
Scheme 15: Co-catalyzed ring-opening/dehydration of oxabicyclic alkenes 30 via C–H activation of arenes.
Scheme 16: Co-catalyzed [3 + 2] annulation/ring-opening/dehydration domino reaction of oxabicyclic alkenes 1 w...
Scheme 17: Co-catalyzed enantioselective carboamination of bicyclic alkenes 1 via C–H functionalization.
Scheme 18: Ru-catalyzed cyclization of oxabenzonorbornene derivatives with propargylic alcohols for the synthe...
Scheme 19: Ru-catalyzed coupling of oxabenzonorbornene derivatives 30 with propargylic alcohols and ethers 106...
Scheme 20: Ru-catalyzed ring-opening/dehydration of oxabicyclic alkenes via the C–H activation of anilides.
Scheme 21: Ru-catalyzed of azabenzonorbornadiene derivatives with arylamides.
Scheme 22: Rh-catalyzed cyclization of bicyclic alkenes with arylboronate esters 118.
Scheme 23: Rh-catalyzed cyclization of bicyclic alkenes with dienyl- and heteroaromatic boronate esters.
Scheme 24: Rh-catalyzed domino lactonization of doubly bridgehead-substituted oxabicyclic alkenes with seconda...
Scheme 25: Rh-catalyzed domino carboannulation of diazabicyclic alkenes with 2-cyanophenylboronic acid and 2-f...
Scheme 26: Rh-catalyzed synthesis of oxazolidinone scaffolds 147 through a domino ARO/cyclization of oxabicycl...
Scheme 27: Rh-catalyzed oxidative coupling of salicylaldehyde derivatives 151 with diazabicyclic alkenes 130a.
Scheme 28: Rh-catalyzed reaction of O-acetyl ketoximes with bicyclic alkenes for the synthesis of isoquinoline...
Scheme 29: Rh-catalyzed domino coupling reaction of 2-phenylpyridines 165 with oxa- and azabicyclic alkenes 30....
Scheme 30: Rh-catalyzed domino dehydrative naphthylation of oxabenzonorbornadienes 30 with N-sulfonyl 2-aminob...
Scheme 31: Rh-catalyzed domino dehydrative naphthylation of oxabenzonorbornadienes 30 with arylphosphine deriv...
Scheme 32: Rh-catalyzed domino ring-opening coupling reaction of azaspirotricyclic alkenes using arylboronic a...
Scheme 33: Tandem Rh(III)/Sc(III)-catalyzed domino reaction of oxabenzonorbornadienes 30 with alkynols 184 dir...
Scheme 34: Rh-catalyzed asymmetric domino cyclization and addition reaction of 1,6-enynes 194 and oxa/azabenzo...
Scheme 35: Rh/Zn-catalyzed domino ARO/cyclization of oxabenzonorbornadienes 30 with phosphorus ylides 201.
Scheme 36: Rh-catalyzed domino ring opening/lactonization of oxabenzonorbornadienes 30 with 2-nitrobenzenesulf...
Scheme 37: Rh-catalyzed domino C–C/C–N bond formation of azabenzonorbornadienes 30 with aryl-2H-indazoles 210.
Scheme 38: Rh/Pd-catalyzed domino synthesis of indole derivatives with 2-(phenylethynyl)anilines 212 and oxabe...
Scheme 39: Rh-catalyzed domino carborhodation of heterobicyclic alkenes 30 with B2pin2 (53).
Scheme 40: Rh-catalyzed three-component 1,2-carboamidation reaction of bicyclic alkenes 30 with aromatic and h...
Scheme 41: Pd-catalyzed diarylation and dialkenylation reactions of norbornene derivatives.
Scheme 42: Three-component Pd-catalyzed arylalkynylation reactions of bicyclic alkenes.
Scheme 43: Three-component Pd-catalyzed arylalkynylation reactions of norbornene and DFT mechanistic study.
Scheme 44: Pd-catalyzed three-component coupling N-tosylhydrazones 236, aryl halides 66, and norbornene (15a).
Scheme 45: Pd-catalyzed arylboration and allylboration of bicyclic alkenes.
Scheme 46: Pd-catalyzed, three-component annulation of aryl iodides 66, alkenyl bromides 241, and bicyclic alk...
Scheme 47: Pd-catalyzed double insertion/annulation reaction for synthesizing tetrasubstituted olefins.
Scheme 48: Pd-catalyzed aminocyclopropanation of bicyclic alkenes 1 with 5-iodopent-4-enylamine derivatives 249...
Scheme 49: Pd-catalyzed, three-component coupling of alkynyl bromides 62 and norbornene derivatives 15 with el...
Scheme 50: Pd-catalyzed intramolecular cyclization/ring-opening reaction of heterobicyclic alkenes 30 with 2-i...
Scheme 51: Pd-catalyzed dimer- and trimerization of oxabenzonorbornadiene derivatives 30 with anhydrides 268.
Scheme 52: Pd-catalyzed Catellani-type annulation and retro-Diels–Alder of norbornadiene 15b yielding fused xa...
Scheme 53: Pd-catalyzed hydroarylation and heteroannulation of urea-derived bicyclic alkenes 158 and aryl iodi...
Scheme 54: Access to fused 8-membered sulfoximine heterocycles 284/285 via Pd-catalyzed Catellani annulation c...
Scheme 55: Pd-catalyzed 2,2-bifunctionalization of bicyclic alkenes 1 generating spirobicyclic xanthone deriva...
Scheme 56: Pd-catalyzed Catellani-type annulation and retro-Diels–Alder of norbornadiene (15b) producing subst...
Scheme 57: Pd-catalyzed [2 + 2 + 1] annulation furnishing bicyclic-fused indanes 281 and 283.
Scheme 58: Pd-catalyzed ring-opening/ring-closing cascade of diazabicyclic alkenes 130a.
Scheme 59: Pd-NHC-catalyzed cyclopentannulation of diazabicyclic alkenes 130a.
Scheme 60: Pd-catalyzed annulation cascade generating diazabicyclic-fused indanones 292 and indanols 294.
Scheme 61: Pd-catalyzed skeletal rearrangement of spirotricyclic alkenes 176 towards large polycyclic benzofur...
Scheme 62: Pd-catalyzed oxidative annulation of aromatic enamides 298 and diazabicyclic alkenes 130a.
Scheme 63: Accessing 3,4,5-trisubstituted cyclopentenes 300, 301, 302 via the Pd-catalyzed domino reaction of ...
Scheme 64: Palladacycle-catalyzed ring-expansion/cyclization domino reactions of terminal alkynes and bicyclic...
Scheme 65: Pd-catalyzed carboesterification of norbornene (15a) with alkynes, furnishing α-methylene γ-lactone...
Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones
- Manuel Pedrón,
- Jana Sendra,
- Irene Ginés,
- Tomás Tejero,
- Jose L. Vicario and
- Pedro Merino
Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37
- the reagent the higher is the barrier (for similar transition-state energies) justifying the observed reactivity. Only the two systems (a and b) with lower values of the integration parameter have barriers compatible with observed reactions upon heating, the rest presenting too high barriers to allow
Graphical Abstract
Scheme 1: Experimental data (series a–d, k) and non-studied examples (series e–j) for transannular cycloaddit...
Figure 1: Optimized (m062x/6-31G(d)) geometries for the transition structures of series a–f.
Figure 2: Top: Cycloaddition of protonated hydrazones as inverse-demand reaction of cycloaddition of azomethi...
Figure 3: Global electron density transfer (GEDT). Dashed black line indicates both TS.
Figure 4: ELF analysis for the reaction of series b leading to a system 6-6. Black trace corresponds to IRC. ...
Figure 5: Quantitative NCI analysis [36] for the reaction of series a–f leading to fused cyclohexanes. The result...
Figure 6: (a) Transannular cycloadditons of compounds 1a–k. (b) Houk’s distortion model applied to the reacti...
Scheme 2: Reaction with simple models.
Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview
- Louis Monsigny,
- Floriane Doche and
- Tatiana Besset
Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35
- 2014, Shen and Xu [117] developed a new methodology for the selective functionalization of 2-arylpyridine derivatives using an electrophilic SCF3 reagent, the Haas reagent I (Scheme 5) [118]. A broad range of 2-arylpyridine derivatives were trifluoromethylthiolated in good to high yields (18 examples
- desired trifluoromethylthiolated product 12 is selectively afforded after a F/SCF3 ligand exchange. In 2015, Ye and Liu reported the palladium-catalyzed trifluoromethylthiolation of 2-arylpyridine derivatives using the Billard reagent II (Scheme 7) [120]. Unlike Shen's methodology (Scheme 5), the use of
- benzoyl chloride was necessary to activate the trifluoromethylthiolated reagent [120]. Unsubstituted and pyridines substituted derivatives 15 were very efficiently ortho-trifluoromethylthiolated (17 examples, up to 91% yield). This methodology was tolerant to electron-donating and electron-withdrawing
Graphical Abstract
Scheme 1: Transition-metal-catalyzed C–XRF bond formation by C–H bond activation: an overview.
Scheme 2: Cu(OAc)2-promoted mono- and ditrifluoromethylthiolation of benzamide derivatives derived from 8-ami...
Scheme 3: Trifluoromethylthiolation of azacalix[1]arene[3]pyridines using copper salts and a nucleophilic SCF3...
Scheme 4: Working hypothesis for the palladium-catalyzed C–H trifluoromethylthiolation reaction.
Scheme 5: Trifluoromethylthiolation of 2-arylpyridine derivatives and analogs by means of palladium-catalyzed...
Scheme 6: C(sp2)–SCF3 bond formation by Pd-catalyzed C–H bond activation using AgSCF3 and Selectfluor® as rep...
Scheme 7: Palladium-catalyzed ortho-trifluoromethylthiolation of 2-arylpyridine derivatives reported by the g...
Scheme 8: Palladium-catalyzed ortho-trifluoromethylthiolation of 2-arylpyridine and analogs reported by Anbar...
Scheme 9: Mono- and ditrifluoromethylthiolation of benzamide derivatives derived from 8-aminoquinoline using ...
Scheme 10: Regioselective Cp*Rh(III)-catalyzed directed trifluoromethylthiolation reported by the group of Li [123]...
Scheme 11: Cp*Co(III)-catalyzed ortho-trifluoromethylthiolation of 2-phenylpyridine and 2-phenylpyrimidine der...
Scheme 12: Cp*Co(III)-catalyzed ortho-trifluoromethylthiolation of 2-phenylpyridine and 6-phenylpurine derivat...
Scheme 13: Diastereoselective trifluoromethylthiolation of acrylamide derivatives derived from 8-aminoquinolin...
Scheme 14: C(sp3)–SCF3 bond formation on aliphatic amide derivatives derived from 8-aminoquinoline by palladiu...
Scheme 15: Regio- and diastereoselective difluoromethylthiolation of acrylamides under palladium catalysis rep...
Scheme 16: Palladium-catalyzed (ethoxycarbonyl)difluoromethylthiolation reaction of 2-(hetero)aryl and 2-(α-ar...
Scheme 17: Pd(II)-catalyzed trifluoromethylselenolation of benzamides derived from 5-methoxy-8-aminoquinoline ...
Scheme 18: Pd(II)-catalyzed trifluoromethylselenolation of acrylamide derivatives derived from 5-methoxy-8-ami...
Scheme 19: Transition-metal-catalyzed dehydrogenative 2,2,2-trifluoroethoxylation of (hetero)aromatic derivati...
Scheme 20: Pd(II)-catalyzed ortho-2,2,2-trifluoroethoxylation of N-sulfonylbenzamides reported by the group of...
Scheme 21: Pd(II)-catalyzed selective 2,2,2-trifluoroethoxylation and other fluoroalkoxylations of naphthalene...
Scheme 22: Pd(II)-catalyzed selective ortho-2,2,2-trifluoroethoxylation of benzaldehyde derivatives by means o...
Scheme 23: Pd(II)-catalyzed selective ortho-2,2,2-trifluoroethoxylation (and other fluoroalkoxylations) of ben...
Scheme 24: Pd(II)-catalyzed selective 2,2,2-trifluoroethoxylation of aliphatic amides using a bidentate direct...
Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities
- Jorge de Lima Neto and
- Paulo Henrique Menezes
Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31
- only be favorable after the macrolactonization step. The authors used a convergent route for the formal synthesis of 2. Reaction of 4-bromobenzaldehyde (52) with a commercially available stabilized Wittig reagent led to the formation of the corresponding ester 53. Further reduction of the carbonyl
- yield diol 72. The 3R,4S configuration of compound 72 was expected based on Pettit’s work [16][17] and the optical purity of the obtained product was more than 95% by 1H NMR using [Eu(hfc)3] as a chiral shift reagent. Subsequent silylation followed by ester hydrolysis and removal of the pivaloyl group
- different types of bases and reaction conditions were used (Scheme 26). Finally, the authors synthesized combretastatin D-4 (4) starting from the Wittig reaction between aldehyde 52 and a commercially available Wittig reagent to give the corresponding α,β-unsaturated ester 123 in quantitative yield
Graphical Abstract
Figure 1: Structures of some members of the combretastatin D series, corniculatolides, and isocorniculatolide...
Scheme 1: Biosynthetic pathway proposed by Pettit and co-workers.
Scheme 2: Biosynthetic pathway towards corniculatolides or isocorniculatolides proposed by Ponnapalli and co-...
Scheme 3: Retrosynthetic approaches.
Scheme 4: Attempt of total synthesis of 2 by Boger and co-workers employing the Mitsunobu approach [27].
Scheme 5: Total synthesis of combretastatin D-2 (2) reported by Boger and co-workers employing an intramolecu...
Scheme 6: Formal synthesis of combretastatin D-2 (2) by Deshpande and co-workers using the Mitsunobu conditio...
Scheme 7: Total synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 8: Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 9: Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41].
Scheme 10: Synthesis of fragment 57 by Couladouros and co-workers [43,45].
Scheme 11: Formal synthesis of compound 2 by Couladouros and co-workers [43,45].
Scheme 12: Synthesis of fragment 66 by Couladouros and co-workers [44,45].
Scheme 13: Synthesis of fragment 70 by Couladouros and co-workers [44,45].
Scheme 14: Synthesis of fragment 77 by Couladouros and co-workers [44,45].
Scheme 15: Synthesis of combretastatins 1 and 2 by Couladouros and co-workers [44,45].
Scheme 16: Formal synthesis of compound 2 by Gangakhedkar and co-workers [48].
Scheme 17: Synthesis of fragment 14 by Cousin and co-workers [50].
Scheme 18: Synthesis of fragment 91 by Cousin and co-workers [50].
Scheme 19: Formal synthesis of compound 2 by Cousin and co-workers [50].
Scheme 20: Synthesis of 2 diolide by Cousin and co-workers [50].
Scheme 21: Synthesis of combretastatin D-4 (4) by Nishiyama and co-workers [54].
Scheme 22: Synthesis of fragment 112 by Pettit and co-workers [55].
Scheme 23: Synthesis of fragment 114 by Pettit and co-workers [55].
Scheme 24: Attempt to the synthesis of compound 2 by Pettit and co-workers [55].
Scheme 25: Synthesis of combretastatin-D2 (2) starting from isovanilin (80) by Pettit and co-workers [55].
Scheme 26: Attempted synthesis of combretastatin-D2 (2) derivatives through an SNAr approach [55].
Scheme 27: Synthesis of combretastatin D-4 (4) by Pettit and co-workers [55].
Scheme 28: Synthesis of combretastatin D-2 (2) by Harras and co-workers [57].
Scheme 29: Synthesis of combretastatin D-4 (4) by Harras and co-workers [57].
Scheme 30: Formal synthesis of combretastatin D-1 (1) by Harras and co-workers [57].
Scheme 31: Synthesis of 11-O-methylcorniculatolide A (5) by Raut and co-workers [69].
Scheme 32: Synthesis of isocorniculatolide A (7) and O-methylated isocorniculatolide A 8 by Raut and co-worker...
Scheme 33: Synthesis of isocorniculatolide B (10) and hydroxyisocorniculatolide B 175 by Kim and co-workers [71].
Scheme 34: Synthesis of compound 9, 178, and 11 by Kim and co-workers [71].
Scheme 35: Synthesis of combretastatin D-2 prodrug salts [55].
Figure 2: ED50 values of the combretastatin D family against murine P388 lymphocytic leukemia cell line (appr...
Figure 3: IC50 of compounds against α-glucosidase [19].
Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis
- Nicoleta G. Hădărugă,
- Gabriela Popescu,
- Dina Gligor (Pane),
- Cristina L. Mitroi,
- Sorin M. Stanciu and
- Daniel Ioan Hădărugă
Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30
- with 300 mL of anhydrous petroleum ether (ACS reagent, 40–60 °C boiling range, Sigma-Aldrich, St. Louis, MO, USA). The extract was distilled and evaporated to dryness until no petroleum ether remained. The oil separation yield was ≈50%. The hazelnut oil was kept at −20 °C until further analyses and β
- ) of the FA glycerides to the corresponding FA methyl esters (FAMEs) [11][13]. The derivatization involved methanol–boron trifluoride (20% BF3), hexane (GC grade) and anhydrous sodium sulfate, all purchased from Merck & Co., Inc., Rahway, NJ, USA. Sodium chloride (reagent grade) used for the separation
- Sigma-Aldrich, St. Louis, MO, USA). Finally, 2-propanol (ACS reagent, Reag. Ph. Eur.) used for FTIR cleaning was obtained from Merck & Co., Inc., Rahway, NJ, USA. Gas chromatography–mass spectrometry (GC–MS) The FA profile of the hazelnut oil was determined by GC–MS, after derivatization to FAMEs
Graphical Abstract
Figure 1: Hypothetical interactions between the β-cyclodextrin host and guest molecules (flavonoid glycoside/...
Figure 2: Superposition of the FTIR spectra for the β-cyclodextrin/Corylus avellana oil/hesperidin ternary co...
Figure 3: Superposition of the FTIR spectra for the β-cyclodextrin/Corylus avellana oil/hesperidin ternary co...
Figure 4: PC2 versus PC1 scores plot from the FTIR–PCA analysis of the flavonoid glycoside and flavonolignan ...
Figure 5: PC2 versus PC1 scores plot from the FTIR–PCA analysis of the β-CD/hazelnut oil/flavonoid ternary co...
Figure 6: PC2 versus PC1 scores plot from the FTIR–PCA analysis of the β-CD/hazelnut oil/flavonoid ternary co...
Figure 7: PC2 versus PC1 scores plot from the FTIR–PCA analysis of the β-CD/hazelnut oil/flavonoid ternary co...
Figure 8: PC3 versus PC1 scores plot from the FTIR-PCA analysis of the β-CD/hazelnut oil/flavonoid ternary co...
Figure 9: PC3 versus PC2 scores plot from the FTIR–PCA analysis of the β-CD/hazelnut oil/flavonoid ternary co...
Figure 10: PC2 versus PC1 loadings plot from the FTIR–PCA analysis of the β-CD/hazelnut oil/flavonoid ternary ...
Figure 11: PC3 versus PC1 loadings plot from the FTIR–PCA analysis of the β-CD/hazelnut oil/flavonoid ternary ...
Figure 12: Eigenvalues of the correlation matrix from the FTIR–PCA analysis of the β-CD/hazelnut oil/flavonoid...
