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Search for "SN2'" in Full Text gives 198 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
- chromatography. Because 4.6 was obtained in better yields and in only 3 steps, the epimerization of 4.6 to 4.10 was also reported (Figure 4B). This epimerization is achieved in three-step sequence that starts with the double tosylation of 4.6 to produce 4.11. Then, the SN2 reaction with potassium acetate in DMSO
- mesylation produced 17.3. Then, the nucleophilic substitution (SN2) reaction of benzoate with 17.3 produced the benzoate ester 17.4 with an inversion of configuration. Then, the two protecting groups (ester and trityl) were removed to produce (S)-17.6. The modification of the sn-2 position is illustrated in
- Figure 17B starting from the mesylate derivative (S)-17.3. Its reaction with sodium azide produced, following a SN2 reaction, the azido derivative 17.7. The deprotection of the alcohol function produced 17.8 that subsequently reacted with 2-chloro-2-oxo-1,3,2-dioxaphospholane (17.9) in the presence of
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
- , such alcohols were in situ converted into the corresponding O-allyl carbamates as leaving groups, followed by their reaction with imidazoles, affording the SN2’ products 3 (Scheme 1, reaction 1, iii). Correlatively, we have previously reported a direct amination of cyclic MBH alcohols 4 with morpholine
- 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
- reaction of the primary five-membered alcohol 4b [29] with imidazole (2a) as well as to that of alcohols 4a,b with benzimidazole (2b), leading to the SN2-type products 6b and 7b,c, respectively, in 55–80% yields (Table 1, entries 7–9). In addition, we have shown that the direct amination of the available
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.
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
- indicative of a carbocationic pathway are not observed, suggesting that RPC does not occur. Further, the inability of ATRA products to undergo SN2 with the added nucleophiles under our reaction conditions is inconsistent with a tandem ARTA/nucleophilic displacement alternative mechanism. Finally, 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...
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
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.
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
- cross-coupling of pyridine N-oxides with nonactivated secondary (2°) alkyl bromides [51]. The cross-coupling is difficult to achieve as the Pd-catalyzed SN2 process is sensitive towards the steric bulk of the secondary or tertiary alkyl electrophiles. The optimized conditions for the ortho-alkylation of
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.
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
- applied to a substrate with a pending bromo substituent (93), the formed enolate 94 underwent a spontaneous cyclization via an SN2 displacement (Scheme 24). The Harutyunyan team showed that this methodology also applies to aza-enolates that are generated by the conjugate addition of Grignard reagents to
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...
A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes
- Alena V. Dmitrieva,
- Oleg A. Levitskiy,
- Yuri K. Grishin and
- Tatiana V. Magdesieva
Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41
- stereoselectivity level. Additionally, Schiff base derivatives of L7 have a considerably higher solubility in acetonitrile as compared to the L4-based complexes (see Table 3 and Supporting Information File 1); this makes it easier to scale-up the synthesis (e.g., for the SN2 alkylations or nucleophilic addition
Graphical Abstract
Scheme 1: Selected examples of the chiral ligands used for synthesis of the Ni(II)–Schiff base complexes.
Scheme 2: Synthesis of the chiral ligand L7 and its Ni(II) complexes with glycine, serine, dehydroalanine, an...
Figure 1: Fragment of the NOESY spectrum of the ʟ-(oBrCysNi)L7 complex indicating the correlation between the...
Figure 2: Low-gradient isosurfaces with low densities (blue color of the isosurface corresponds to the hydrog...
Figure 3: Saturated solutions of (GlyNi)L1 (left) and (GlyNi)L7 (right) in diethyl ether.
Figure 4: The CV curves observed for (GlyNi)L7 and (ΔAlaNi)L7 in the anodic and cathodic regions (Pt, CH3CN, ...
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
- ]-sigmatropic rearrangement of the diazabicycle 47 to form the allylic carbazate intermediate 51. Nucleophilic attack of an organomagnesium, or organocuprate, in an anti SN2’ fashion on 52 furnish the final ring-opened product 49. The authors note the use of a carbamate protecting group was crucial for the
- then nucleophillically attacks the alkene in an SN2’ fashion producing the trans-isocyanate 149. Subsequently, insertion of the Rh–O bond into the isocyanate results in 150. Finally, protonolysis produces the oxazolidinone product 147e as well as regenerates the active Rh(I) catalyst. In 2013, the
- to other ARO reactions, the catalytic cycle is proposed to begin with the oxidative insertion of the Rh(I) catalyst into the bridgehead C–O bond producing 204. The phosphorus ylide attacks 204 in an SN2’ fashion on the endo face giving the ring-opened 205 as well as regenerating the Rh(I) catalyst
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...
Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr4/PPh3 and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior
- Christian Schumacher,
- Jas S. Ward,
- Kari Rissanen,
- Carsten Bolm and
- Mohamed Ramadan El Sayed Aly
Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9
- from the stereochemistry of the standard Appel mechanism due to participation of the Δ5 π-electrons. In contrast, the subsequent azidolysis (NaN3/DMF) of 3β-bromocholest-5-ene proceeds predominantly by Walden inversion (SN2) affording 3α-azidocholest-5-ene. The structures of all relevant products were
Graphical Abstract
Figure 1: Chemical structure of three isomeric cholesterols.
Figure 2: Selected previously described cholesterol derivatives with interesting antibacterial and cytotoxic ...
Scheme 1: Stereochemical outcome of OH/N3 transformations under different conditions.
Figure 3: Top: cholesterol (1) and the less polar product from the Appel reaction, cholesta-3,5-diene (9); bo...
Figure 4: Top: the more polar product from the Appel reaction 3β-bromocholest-5-ene (4); bottom: X-ray struct...
Figure 5: Top: 3α-azidocholest-5-ene (5) obtained by treatment of 4 with NaN3 in DMF; bottom: X-ray crystal s...
Scheme 2: Mechanistic interpretation of the conversion of cholesterol 1 into diene 9, bromide 4, and azides 5...
Figure 6: Compounds (next to 4, 5 and 9) to be corrected in refs. [10] and [11]. The respective bonds are highlighted...
Combining the best of both worlds: radical-based divergent total synthesis
- Kyriaki Gennaiou,
- Antonios Kelesidis,
- Maria Kourgiantaki and
- Alexandros L. Zografos
Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1
- 167 at 390 nm in the presence of NaHCO3 in CH3CN/t-BuOH, 5:1 to provide 168 in 55% yield (Scheme 14) [91]. Alkylation of the tetracycle, followed by epimerization of the C2 center and radical deoxygenation, or alternatively SN2 etherification, provided the common scaffold 170. The latter can serve as
Graphical Abstract
Scheme 1: The power of radical retrosynthesis and the tactic of divergent total synthesis.
Figure 1: Evolution of radical chemistry for organic synthesis.
Scheme 2: Divergent total synthesis of α-pyrone-diterpenoids (Baran).
Scheme 3: Divergent synthesis of pyrone diterpenoids by merged chemoenzymatic and radical synthesis (part I, ...
Scheme 4: Divergent synthesis of pyrone diterpenoids by merged chemoenzymatic and radical synthesis (part II,...
Scheme 5: Divergent synthesis of drimane-type hydroquinone meroterpenoids (Li).
Scheme 6: Divergent synthesis of natural products isolated from Dysidea avara (Lu).
Scheme 7: Divergent synthesis of kaurene-type terpenoids (Lei).
Scheme 8: Divergent synthesis of 6-oxabicyclo[3.2.1]octane meroterpenoids (Lou).
Scheme 9: Divergent synthesis of crinipellins by radical-mediated Dowd–Backwith rearrangement (Xie and Ding).
Scheme 10: Divergent total synthesis of Galbulimima alkaloids (Shenvi).
Scheme 11: Divergent synthesis of eburnane alkaloids (Qin).
Scheme 12: Divergent synthesis of Aspidosperma alkaloids (Boger).
Scheme 13: Photoredox based synthesis of (−)-FR901483 (160) and (+)-TAN1251C (162, Gaunt).
Scheme 14: Divergent synthesis of bipolamines (Maimone).
Scheme 15: Flow chemistry divergency between aporphine and morphinandione alkaloids (Felpin).
Scheme 16: Divergent synthesis of pyrroloazocine natural products (Echavarren).
Scheme 17: Using TEMPO to stabilize radicals for the divergent synthesis of pyrroloindoline natural products (...
Scheme 18: Radical pathway for preparation of lignans (Zhu).
Scheme 19: Divergent synthesis of DBCOD lignans (Lumb).
Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol
- Emine Salamci and
- Ayse Kilic Lafzi
Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163
- group in compound 10 was converted to the corresponding alcohol 11 as the sole isomer via SN2 substitution by hydrolysis. In the azidolysis reaction of compound 8, we propose that because the azide group is bulkier than the water molecule, it could not substitute the second mesylate group, and therefore
Graphical Abstract
Figure 1: Some biologically active aziridine-bearing compounds 1, 2 and aminocyclitol 3.
Scheme 1: Synthesis of dimesylate 8.
Scheme 2: Synthesis of aminocyclooctanetriol 13.
Scheme 3: Synthesis of aziridinecyclooctanediol 16.
A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles
- Pavel A. Topanov,
- Anna A. Maslivets,
- Maksim V. Dmitriev,
- Irina V. Mashevskaya,
- Yurii V. Shklyaev and
- Andrey N. Maslivets
Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162
- negatively charged [38] C(3) atom of diazooxindoles 2 at the C(3a) atom of FPDs 1 (Scheme 5), and (b) further intramolecular SN2 attack by the oxygen of the aroyl group with ensuing elimination of a nitrogen molecule. To verify our assumption, 3-bromooxindole (4) was involved in the reaction with FPD 1i in
- the presence of 1.1 equiv of TEA. In this case, the base-promoted deprotonation of 3-bromooxindole (4) affords a highly nucleophilic intermediate, which undergoes Michael addition to FPD 1i, followed by intramolecular SN2 attack [39][40][41][42][43] by the oxygen of the aroyl group (Scheme 5) to give
Graphical Abstract
Figure 1: Selected examples of biologically active natural products bearing a spirofuranoxindole moiety.
Scheme 1: Synthesis of spiro[dihydrofuran-2,3'-oxindoles] from enones and diazooxindoles.
Scheme 2: Cycloaddition reactions of [e]-fused 1H-pyrrole-2,3-diones.
Scheme 3: The model reaction of FPD 1a and diazooxindole 2a.
Scheme 4: The reaction of FPD 1k with diazooxindole 2a.
Scheme 5: A) Plausible mechanism of formal [4 + 1] cycloaddition of FPDs 1 with diazooxindoles 2 (negative ch...
Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions
- Michael Keppler,
- Sandra Moser,
- Henning J. Jessen,
- Christoph Held and
- Jennifer N. Andexer
Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134
- ADP for an in-line reaction of these two substrates. Out of this arrangement two reaction pathways have been discussed, an associative and a dissociative one. The associative one is an SN2-like attack of ADP on the terminal phosphate of the polyP chain, while the dissociative one is an SN1-like
Graphical Abstract
Figure 1: Polyphosphate, a ubiquitous phosphate storage molecule. Reported chain lengths range from three to ...
Figure 2: Comparison of PPK1 and PPK2 enzymes. a) Reaction scheme; b) structure of the EcPPK1 monomer (PDB 1X...
Figure 3: a) Kinases as ATP regeneration enzymes, exemplified by the hexokinase-catalysed ATP-dependent phosp...
Figure 4: Time courses of reactions started with ADP catalysed by a) SmPPK2 and b) EcPPK1. Time courses of re...
Figure 5: a) Ratio of product to substrate for the three nucleotide concentrations (0.5, 2, and 4 mM) used in...
Figure 6: Time courses comparing EcPPK1 (blue) and SmPPK2 (green) for ATP synthesis (a) and ATP degradation (...
Ferrocenoyl-adenines: substituent effects on regioselective acylation
- Mateja Toma,
- Gabrijel Zubčić,
- Jasmina Lapić,
- Senka Djaković,
- Davor Šakić and
- Valerije Vrček
Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133
- /bjoc.18.133 Abstract A series of N6-substituted adenine–ferrocene conjugates was prepared and the reaction mechanism underlying the synthesis was explored. The SN2-like reaction between ferrocenoyl chloride and adenine anions is a regioselective process in which the product ratio (N7/N9-ferrocenoyl
- -TSN7 and 6-TSN9 (Figure 4) are characterized by one imaginary frequency (134i and 163i cm−1, respectively), which corresponds to the N–C bond formation concomitant with C–Cl bond breaking. Both structures support a concerted SN2-type mechanism in which a tetrahedral intermediate does not exist
- present in the transition structure 6-TSN9, which is, as reported above, more stable (11.3 kJ/mol) than the structure 6-TSN7. It comes out that the regioselectivity of the ferrocenoylation of adenine anion 6 is kinetically controlled, mostly due to steric effects. The same SN2-type mechanism is operative
Graphical Abstract
Scheme 1: Regioselective ferrocenoylation of the adenine anion 1 and its derivatives 2–6 substituted at the N6...
Figure 1: 1H NMR spectrum (downfield region) of the reaction mixture (adenine anion 1 and FcCOCl) in DMF, tak...
Figure 2: HOMO map of space distribution (left) of adenine anion (1) at the B3LYP/6-31+G(d) level of theory (...
Figure 3: Dependence of N9-isomer product ratio (%), in the reaction between FcCOCl and adenine anions 1–6, o...
Figure 4: B3LYP/6-31+G(d)/SDD optimized transition state structures for N7- (6-TSN7) and N9-ferrocenoylation (...
Figure 5: Relation between the Gibbs free energy barrier (ΔG‡) for the N7-ferrocenoylation of C6-substituted ...
Polymer and small molecule mechanochemistry: closer than ever
- José G. Hernández
Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128
- to promote the thermodynamically disfavored SN2 cleavage of an individual protein disulfide bond by poorly nucleophilic organic thiols [21]. On the other hand, as for the connection or correlation between polymer and small molecule mechanochemistry, this Perspective article discusses recent studies
Graphical Abstract
Figure 1: Representation of (a) cavitation and elongational flow caused by pulsed ultrasonication, (b) mixer ...
Scheme 1: (a) Mechanochemical activation of anthracene–endoperoxide mechanophore incorporated in the cross-li...
Scheme 2: Mechanochemical activation of dendronized polymer-based compound 4 by ultrasonication and ball mill...
Figure 2: Structure of cellulose and chitin and approximation to the structure of lignin.
Figure 3: Tensile forces by ball milling change the conformation of a chitin model compound. This deformation...
Figure 4: (a) Representation of a collision between the ball and a particle of a chitin sample and (b) mechan...
Figure 5: (a) Ultrasound-induced ATRP using piezoelectric BaTiO3 and (b) mechanochemical atom transfer radica...
Figure 6: Mechanochemical solid-state complexation of organic capsule 5 with fullerenes C70 in a planetary ba...
Scheme 3: Comparative mechanochemical dissociation of the central C–C bond in TASN derivatives 6 and 8.
Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics
- Durbis J. Castillo-Pazos,
- Juan D. Lasso and
- Chao-Jun Li
Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79
- , while other synthetic approaches were explored to obtain these reagents, the SN2 strategy described in this work was the most efficient. Such synthetic alternatives included: first, a sulfur(VI) fluoride exchange (SuFEx) between perfluoroalkylsulfonyl fluorides and the corresponding silyl enol ether
Graphical Abstract
Scheme 1: Envisioned Minisci perfluoroalkylation facilitated by “dummy group” reagents 1a–c.
Scheme 2: Control experiments for the nucleophilic substitution of perfluoroalkylsulfinates 2 and halogenated...
Scheme 3: Left: isolated yields of synthesized perfluoroalkylating reagents: perfluorobutyl (1a), perfluorohe...
Scheme 4: Radical trapping experiment with 1,1-diphenylethylene (7) and 1b confirming the initially proposed ...
Scheme 5: Demonstrative scope for the perfluoroalkylation of aromatics. Isolated yields are shown in parenthe...
Site-selective reactions mediated by molecular containers
- Rui Wang and
- Yang Yu
Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35
- . DMSO was introduced as a co-solvent to promote the SN2-type reaction, and the dibromide 49 was smoothly hydrolyzed site-selectively to the monohydroxy product 50, which was fixed in an unsymmetrical manner in the cavitand. The bromide terminal was hence protected deep within the cavity of the cavitand
Graphical Abstract
Figure 1: Site-selective Diels–Alder reaction of anthracene and phthalimide mediated by aqueous organopalladi...
Figure 2: Site-selective Diels–Alder and [2 + 2]-photoaddition reactions between naphthalene and phthalimide ...
Figure 3: Cage host A-mediated selective 1,4-radical addition of o-quinone 10.
Figure 4: Cyclodextrin-mediated site-selective reductions.
Figure 5: Selective reduction of an α,ω-diazide compound mediated by water-soluble cavitand D.
Figure 6: Selective radical reduction of α,ω-dihalides mediated by water-soluble cavitands E and F.
Figure 7: Site-selective hydrogenation of polyenols mediated by supramolecular encapsulated rhodium catalyst.
Figure 8: Site-selective oxidation of steroids using cyclodextrin as the anchoring template.
Figure 9: Site-selective oxidations of linear diterpenoids with the help of cage host A.
Figure 10: Site-selective monoepoxidation of α,ω-dienes mediated by the water-soluble cavitand host E.
Figure 11: Site-selective ring-opening reaction of epoxides mediated by cavitand I with an inwardly directed c...
Figure 12: Site-selective nucleophilic substitution reaction of allylic chlorides mediated by cage host J.
Figure 13: Site-selective monohydrolysis of α,ω-difunctional compounds using deep water-soluble cavitands.
Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides
- Malcolm J. D’Souza and
- Dennis N. Kevill
Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13
- changes observed as the water content increased were consistent with an SN2 reaction becoming a mixed SN2–SN1 situation and then, eventually, an essentially SN1 pathway was followed. It was concluded that nucleophilic attack at sulfur has many of the characteristics of attack at carbon, including the
- interplay of SN1 and SN2 pathways for attack at a saturated carbon atom being carried over to attack at sulfur(VI). From the experiments reported by Vizgert and Savchuk [15], we will choose just one of the many possibilities for an application of the Hammett equation [5][6]. Applying to the rate data in 30
- aqueous dioxane, aqueous acetone, methanol/acetone, and ethanol/acetone, the p-NO2 (strongest electron-withdrawing influence) was always reacting faster than the parent and the other two derivatives and the overall behavior in a Hammett equation treatment indicated that all were reacting by an SN2 pathway
Graphical Abstract
Scheme 1: Organic reactions where the breaking of a C–X bond involves the formation of a high energy ion-pair...
Scheme 2: The chemical structures for the 1-adamantyl substrate, 2-adamantyl substrate, and the S-methyldiben...
Figure 1: The SN2 reaction plot of log (k/ko) vs (1.26 NT + 0.65 YCl) for the solvolyses of benzesulfonyl chl...
Figure 2: The SN2 reaction plot of log (k/ko) vs (1.35 NT + 0.70 YCl) for the solvolyses of 2-thiophenesulfon...
Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues
- Sandeep Kumar,
- Jyotirmoy Maity,
- Banty Kumar,
- Sumit Kumar and
- Ashok K. Prasad
Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10
- from the C6′-OH group (Scheme 6). The second inversion at the C5′ centre occurred when the C2′-OH attacked the same chiral centre and opened the epoxide ring by SN2 reaction and inverted the configuration of the centre into (R). In the chemical route for synthesis of bridged nucleosides 9a,b, an
- possible sequence to explain the progress of the reaction (Scheme 6). The sequence of the intermediates also described that epoxide formation occurred after removal of TBDPS and then attack from C2′-OH happened at the C5′ centre, i.e., two consecutive SN2 reactions at the C5′ centre, which retained the
Graphical Abstract
Figure 1: Structure of AZT and representative related bicyclic nucleosides.
Scheme 1: Retrosynthetic routes for the synthesis of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabin...
Scheme 2: Synthesis of 3′-azido-3′-deoxy-β-ᴅ-allofuranosylthymine (14a) and -uracil (14b).
Scheme 3: Biocatalytic acetylation of the primary hydroxy group of nucleosides 14a,b.
Scheme 4: Synthesis of (5'R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosyl nucleosides 9a,b.
Scheme 5: Chemical synthesis of nucleosides 9a,b starting from diacetone ᴅ-glucofuranose.
Figure 2: Structure elucidation of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosylthymine (...
Scheme 6: a) Plausible mechanism for the synthesis of (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabi...
Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation
- Lukáš Ďurina,
- Anna Ďurinová,
- František Trejtnar,
- Ľuboš Janotka,
- Lucia Messingerová,
- Jana Doháňošová,
- Ján Moncol and
- Róbert Fischer
Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188
- be prepared by substrate-directed epoxidation. A subsequent SN2 intramolecular epoxide ring-opening cyclization could provide an N-Cbz-protected pyrrolidine derivative with a hydroxymethyl group at C-5 and with trans configuration relative to the hydroxy group at C-4. Finally, (±)-codonopsinol B (1
Graphical Abstract
Figure 1: (−)-Codonopsinol B (1) and its N-nor-methyl analogue 2; known inhibition activities against α-gluco...
Scheme 1: Synthetic approach towards (±)-codonopsinol B (1) and its N-nor-methyl analogue 2.
Scheme 2: Synthesis of isoxazolidine-4,5-diol (±)-3. Reagents and conditions: (a) ᴅʟ-proline, CHCl3, rt, 48 h...
Scheme 3: Synthesis of final pyrrolidines (±)-1 and (±)-2. Reagents and conditions: (a) vinyl-MgBr, CeCl3, TH...
Figure 2: Molecular structure of N-Cbz-protected pyrrolidine 12 confirmed by single-crystal X-ray crystallogr...
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
- the stable oxonium ion to provide an anomer, which further reacts with the presilylated nucleobase in an SN2 manner and predominantly affords the β-cytidine adduct. DKR overcomes the drawback of classical resolution since it is theoretically possible to obtain 100% yield of the desired isomer [74]. 5
- carbon atom while maintaining α-configuration and simultaneous elimination of an acyl group as illustrated in intermediate IV. Further, attack of silylated cytosine on α-chloro-substituted derivative V in an SN2 reaction results in the formation of a glycosidic C–N bond in the β-configured nucleoside
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.
Direct C(sp3)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement
- Siyu Wang,
- Lianyou Zheng,
- Shutao Wang,
- Shulin Ning,
- Zhuoqi Zhang and
- Jinbao Xiang
Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167
- (sp3)–H allylic alkylation of 2-alkylpyridines with Morita–Baylis–Hillman (MBH) carbonates is described. A plausible mechanism of the reaction might involve a tandem SN2’ type nucleophilic substitution followed by an aza-Cope rearrangement. Various alkyl substituents on 2-alkylpyridines were tolerated
- our studies on a direct benzylic allylic reaction of 2-alkylpyridines with MBH carbonates as allylic precursors under base- and catalyst-free conditions. As depicted in Scheme 2, we envisioned that the MBH carbonate 2 can undergo the SN2’ reaction with the nucleophilic 2-picoline 1a, giving the
- intramolecular SN2’ type reaction (path a) or an aza-Cope rearrangement under thermal conditions to generate product 3. Results and Discussion To evaluate our idea for the allylic alkylation reaction of MBH carbonates to 2-alkylpyridines, 2-picoline (1a) and MBH carbonate 2a were selected as the model substrates
Graphical Abstract
Scheme 1: The benzylic C(sp3)–H allylic alkylation reactions of 2-alkylpyridines.
Scheme 2: Mechanistic hypothesis of the alkylation reaction of 2-alkylpyridines with MBH carbonates.
Scheme 3: Scope of MBH carbonates 2 with 2-picoline 1a. The reactions were performed using 1a (1.0 mmol, 2 eq...
Scheme 4: Scope of 2-alkylpyridine 1 with MBH carbonate 2a. The reactions were performed using 1 (1.0 mmol, 2...
Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds
- Sumana Mandal,
- Raju D. Chaudhari and
- Goutam Biswas
Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153
- proved that the reaction mechanism proceeds via activation of the alkynyl group with Hg(OTf)2 salt and addition of 2-chloropyridine N-oxide. The resulting activated alkynyl complex was demercurated, followed by the SN2′ reaction thus formed undergoes demercuration to yield 3-coumaranone (Scheme 51) [111
Graphical Abstract
Scheme 1: Schematic representation of Hg(II)-mediated addition to an unsaturated bond.
Scheme 2: First report of Hg(II)-mediated synthesis of 2,5-dioxane derivatives from allyl alcohol.
Scheme 3: Stepwise synthesis of 2,6-distubstituted dioxane derivatives.
Scheme 4: Cyclization of carbohydrate alkene precursor.
Scheme 5: Hg(II)-mediated synthesis of C-glucopyranosyl derivatives.
Scheme 6: Synthesis of C-glycosyl amino acid derivative using Hg(TFA)2.
Scheme 7: Hg(OAc)2-mediated synthesis of α-ᴅ-ribose derivative.
Scheme 8: Synthesis of β-ᴅ-arabinose derivative 18.
Scheme 9: Hg(OAc)2-mediated synthesis of tetrahydrofuran derivatives.
Scheme 10: Synthesis of Hg(TFA)2-mediated bicyclic nucleoside derivative.
Scheme 11: Synthesis of pyrrolidine and piperidine derivatives.
Scheme 12: HgCl2-mediated synthesis of diastereomeric pyrrolidine derivatives.
Scheme 13: HgCl2-mediated cyclization of alkenyl α-aminophosphonates.
Scheme 14: Cyclization of 4-cycloocten-1-ol with Hg(OAc)2 forming fused bicyclic products.
Scheme 15: trans-Amino alcohol formation through Hg(II)-salt-mediated cyclization.
Scheme 16: Hg(OAc)2-mediated 2-aza- or 2-oxa-bicyclic ring formations.
Scheme 17: Hg(II)-salt-induced cyclic peroxide formation.
Scheme 18: Hg(OAc)2-mediated formation of 1,2,4-trioxanes.
Scheme 19: Endocyclic enol ether derivative formation through Hg(II) salts.
Scheme 20: Synthesis of optically active cyclic alanine derivatives.
Scheme 21: Hg(II)-salt-mediated formation of tetrahydropyrimidin-4(1H)-one derivatives.
Scheme 22: Cyclization of ether derivatives to form stereoselective oxazolidine derivatives.
Scheme 23: Cyclization of amide derivatives induced by Hg(OAc)2.
Scheme 24: Hg(OAc)2/Hg(TFA)2-promoted cyclization of salicylamide-derived amidal auxiliary derivatives.
Scheme 25: Hg(II)-salt-mediated cyclization to form dihydrobenzopyrans.
Scheme 26: HgCl2-induced cyclization of acetylenic silyl enol ether derivatives.
Scheme 27: Synthesis of exocyclic and endocyclic enol ether derivatives.
Scheme 28: Cyclization of trans-acetylenic alcohol by treatment with HgCl2.
Scheme 29: Synthesis of benzofuran derivatives in presence of HgCl2.
Scheme 30: a) Hg(II)-salt-mediated cyclization of 4-hydroxy-2-alkyn-1-ones to furan derivatives and b) its mec...
Scheme 31: Cyclization of arylacetylenes to synthesize carbocyclic and heterocyclic derivatives.
Scheme 32: Hg(II)-salt-promoted cyclization–rearrangement to form heterocyclic compounds.
Scheme 33: a) HgCl2-mediated cyclization reaction of tethered alkyne dithioacetals; and b) proposed mechanism.
Scheme 34: Cyclization of aryl allenic ethers on treatment with Hg(OTf)2.
Scheme 35: Hg(TFA)2-mediated cyclization of allene.
Scheme 36: Hg(II)-catalyzed intramolecular trans-etherification reaction of 2-hydroxy-1-(γ-methoxyallyl)tetrah...
Scheme 37: a) Cyclization of alkene derivatives by catalytic Hg(OTf)2 salts and b) mechanism of cyclization.
Scheme 38: a) Synthesis of 1,4-dihydroquinoline derivatives by Hg(OTf)2 and b) plausible mechanism of formatio...
Scheme 39: Synthesis of Hg(II)-salt-catalyzed heteroaromatic derivatives.
Scheme 40: Hg(II)-salt-catalyzed synthesis of dihydropyranone derivatives.
Scheme 41: Hg(II)-salt-catalyzed cyclization of alkynoic acids.
Scheme 42: Hg(II)-salt-mediated cyclization of alkyne carboxylic acids and alcohol to furan, pyran, and spiroc...
Scheme 43: Hg(II)-salt-mediated cyclization of 1,4-dihydroxy-5-alkyne derivatives.
Scheme 44: Six-membered morpholine derivative formation by catalytic Hg(II)-salt-induced cyclization.
Scheme 45: Hg(OTf)2-catalyzed hydroxylative carbocyclization of 1,6-enyne.
Scheme 46: a) Hg(OTf)2-catalyzed hydroxylative carbocyclization of 1,6-enyne. b) Proposed mechanism.
Scheme 47: a) Synthesis of carbocyclic derivatives using a catalytic amount of Hg(II) salt. b) Proposed mechan...
Scheme 48: Cyclization of 1-alkyn-5-ones to 2-methylfuran derivatives.
Scheme 49: Hg(NO3)2-catalyzed synthesis of 2-methylenepiperidine.
Scheme 50: a) Preparation of indole derivatives through cycloisomerization of 2-ethynylaniline and b) its mech...
Scheme 51: a) Hg(OTf)2-catalyzed synthesis of 3-indolinones and 3-coumaranones and b) simplified mechanism.
Scheme 52: a) Hg(OTf)2-catalyzed one pot cyclization of nitroalkyne and b) its plausible mechanism.
Scheme 53: Synthesis of tricyclic heterocyclic scaffolds.
Scheme 54: HgCl2-mediated cyclization of 2-alkynylphenyl alkyl sulfoxide.
Scheme 55: a) Hg(OTf)2-catalyzed cyclization of allenes and alkynes. b) Proposed mechanism of cyclization.
Scheme 56: Stereoselective synthesis of tetrahydropyran derivatives.
Scheme 57: a) Hg(ClO4)2-catalyzed cyclization of α-allenol derivatives. b) Simplified mechanism.
Scheme 58: Hg(TFA)2-promoted cyclization of a γ-hydroxy alkene derivative.
Scheme 59: Synthesis Hg(II)-salt-mediated cyclization of allyl alcohol for the construction of ventiloquinone ...
Scheme 60: Hg(OAc)2-mediated cyclization as a key step for the synthesis of hongconin.
Scheme 61: Examples of Hg(II)-salt-mediated cyclized ring formation in the syntheses of (±)-fastigilin C and (...
Scheme 62: Formal synthesis of (±)-thallusin.
Scheme 63: Total synthesis of hippuristanol and its analog.
Scheme 64: Total synthesis of solanoeclepin A.
Scheme 65: a) Synthesis of Hg(OTf)2-catalyzed azaspiro structure for the formation of natural products. b) Pro...
Base-free enantioselective SN2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis
- Mili Litvajova,
- Emiliano Sorrentino,
- Brendan Twamley and
- Stephen J. Connon
Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146
- highly valuable synthetic building blocks [5][6][7][8][9][10][11][12]. Both pyrroloindolines 1 and spirooxindoles 2 are conceivably available from key 3,3-disubstituted intermediates 3, which could be prepared via an enantioselective SN2 alkylation involving enolate 3a (Figure 1B). The versatility of
- charged intermediates, could be an excellent methodology for the enantioselective SN2 alkylation of enolates derived from the 2-oxindole core [13][14][15][16][17][18][19][20][21][22][23]. In recent years, several examples regarding the alkylation of 3-subsituted-2-oxindoles, via asymmetric phase-transfer
- the SN2 alkylation of methylene ester-substituted 2-oxindole 4 [31]. The utility of this methodology has been demonstrated through the total synthesis of (−)-debromoflustramine B (Scheme 1B). In an attempt to devise variants of this reaction of greater versatility and synthetic utility; we sought to
Graphical Abstract
Figure 1: The importance of the 3,3-spirooxindole core and its access through enantioselective enolate alkyla...
Scheme 1: A) SN2 alkylation of 3-subtituted-2-oxindoles not readily functionalisable; B) Previous work: enant...
Figure 2: Substrate scope. aIsolated yield. bDetermined by CSP-HPLC. cValue in brackets refers to reaction co...
Scheme 2: Enantioselective synthesis of a CRTH2 receptor antagonist.
Halides as versatile anions in asymmetric anion-binding organocatalysis
- Lukas Schifferer,
- Martin Stinglhamer,
- Kirandeep Kaur and
- Olga García Macheño
Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145
- participates in the ionization step by an anion abstraction-type process (Figure 2b). In the latter approach, the C–X bond cleavage can then either follow a SN1 or SN2 pathway. For enantioselective purposes, solvation of the ion pair is crucial for obtaining high stereoinduction. While more polar solvents give
- -bonding to the carbonyl group was proposed as the binding mode of the catalyst and the reaction to proceed via a SN2-type mechanism (Scheme 2b, left). Not considered at that time was the anion-binding pathway through the iminium chloride salt II, which would proceed via a SN1-type mechanism (Scheme 2b
- cyclization reaction of succinimide and glutarimide-derived hydroxylactams 7 (Scheme 3) [33]. This system was designed in a way that key experimental observations could be made to analyze whether a SN1 or SN2-type mechanism takes place. A strong dependence of the enantioselectivity on the counterion and
Graphical Abstract
Figure 1: a) Binding interactions in the chloride channel of E. coli. and b) examples of chloride, cyanide, n...
Figure 2: a) H-bond vs anion-binding catalysis and b) activation modes in anion-binding catalysis.
Scheme 1: First proposed anion-binding mechanism in the thiourea-catalyzed acetalization of benzaldehyde.
Scheme 2: a) Thiourea-catalyzed enantioselective acyl-Pictet–Spengler reaction of tryptamine-derived imines 4...
Scheme 3: Proposed mechanism of the thiourea-catalyzed enantioselective Pictet–Spengler reaction of hydroxyla...
Scheme 4: a) Thiourea-catalyzed intramolecular Pictet–Spengler-type cyclization of hydroxylactam-derived N-ac...
Scheme 5: Enantioselective Reissert-type reactions of a) (iso)quinolines with silyl ketene acetals, and b) vi...
Figure 3: Role of the counter-anion: a) Anion acting as a spectator and b) anion participating directly as th...
Scheme 6: Enantioselective selenocyclization catalyzed by squaramide 28.
Scheme 7: Desymmetrization of meso-aziridines catalyzed by bifunctional thiourea catalyst 31.
Scheme 8: Anion-binding-catalyzed desymmetrization of a) meso-aziridines catalyzed by chiral triazolium catal...
Scheme 9: Bis-urea-catalyzed enantioselective fluorination of a) β-bromosulfides and b) β-haloamines by Gouve...
Scheme 10: a) Bifunctional thiourea anion-binding – basic/nucleophilic catalysts. Selected applications in b) ...
Scheme 11: Thiourea-catalyzed enantioselective polycyclization reaction of hydroxylactams 51 through cation–π ...
Scheme 12: Enantioselective aza-Sakurai cyclization of hydroxylactams 56 implicating additional cation–π and L...
Scheme 13: Enantioselective tail-to-head cyclization of neryl chloride derivatives.
Scheme 14: Cation–π interactions in anion binding-catalyzed asymmetric addition reactions: a) addition of indo...
Scheme 15: Bisthiourea catalyzed oxa-Pictet–Spengler reaction of indole-based alcohols and aromatic aldehydes ...
Scheme 16: Anion-binding catalyst development in the enantioselective addition of silyl ketene acetals to 1-ch...
Scheme 17: a) Macrocyclic bis-thiourea catalyst in a diastereoselective glycosylation reaction. b) Competing SN...
Scheme 18: a) Folding mechanism of oligotriazoles upon anion recognition. b) Representative tetratriazole 82 c...
Scheme 19: Switchable chiral tetratriazole catalyst 86 in the enantioselective addition of silyl ketene acetal...
