Search results
Search for "alkylation" in Full Text gives 600 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate
- Mysore Bhyrappa Harisha,
- Pandi Dhanalakshmi,
- Rajendran Suresh,
- Raju Ranjith Kumar and
- Shanmugam Muthusubramanian
Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178
- just at the start of the reaction and b is the photograph after the completion of the reaction. Further, the utility of the thiol group in 3 for the generation of a library of compounds was demonstrated by the simple acetylation and alkylation (Scheme 4 and Scheme 5). The acetylation of the thiol group
Graphical Abstract
Figure 1: Examples of biologically active oxazole and aminothiazole scaffolds.
Scheme 1: Strategies for the synthesis of 2,4,5-trisubstituted oxazole from azirine. a) I2, PPh3; b) NaH, 1H-...
Scheme 2: Scope of the α-azidochalcones. The reactions were carried out at reflux temperature, using 1 (1 mmo...
Scheme 3: Large-scale synthesis of 3i.
Figure 2: Large-scale synthesis of 3i. a) At the start of the reaction, b) after the reaction.
Scheme 4: Acetyl derivative of 3d.
Figure 3: ORTEP diagram of compound 5.
Scheme 5: Synthesis of S-methyl/benzylated products 6 and 7.
Scheme 6: Control experiments.
Scheme 7: Plausible mechanism proposed for the formation of 2,4,5-trisubstituted oxazoles 3.
Scheme 8: Reaction of vinyl azide 1 and 3 with ferric nitrate. Reactions were carried out at reflux temperatu...
Figure 4: X-ray crystal structure of 4h.
Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction
- Alexander N. Reznikov,
- Dmitry S. Nikerov,
- Anastasiya E. Sibiryakova,
- Victor B. Rybakov,
- Evgeniy V. Golovin and
- Yuri N. Klimochkin
Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174
- presence of Pd/C. However, phosphonate 7 was unstable: already during its isolation, it was partially transformed into compounds 8 and 9. It can be assumed that N-alkylation by the phosphoryl group occurs [47][48][49]. To avoid this undesirable process, the product 7 was formylated before its isolation
Graphical Abstract
Figure 1: Pharmacologically active nonracemic phosphonates with heterocyclic moieties.
Figure 2: Starting nonracemic 4-nitro-2-oxophosphonates.
Scheme 1: Intermolecular N-methylation of reduction product 7.
Scheme 2: Synthesis of pyrrolidinyl phosphonic acids 11a–d.
Figure 3: ORTEP diagram of (2R,3R,4S)-10a.
Scheme 3: Synthesis of tetrahydropyranylphosphonates 13a–f via diastereoselective Henry/acetalyzation reactio...
Figure 4: ORTEP diagram of (2S,3R,4S,5S,6R)-13b.
Scheme 4: Synthesis of (3,4-dihydro-2H-pyran-5-yl)phosphonate 14.
Synthesis of 3(2)-phosphonylated thiazolo[3,2-a]oxopyrimidines
- Ksenia I. Kaskevich,
- Anastasia A. Babushkina,
- Vladislav V. Gurzhiy,
- Dmitrij M. Egorov,
- Nataly I. Svintsitskaya and
- Albina V. Dogadina
Beilstein J. Org. Chem. 2020, 16, 1947–1954, doi:10.3762/bjoc.16.161
- most accessible approach to the synthesis of 5H-thiazolo[3,2-a]pyrimidine-5(7)-ones is the reaction of 2-thiouracil derivatives with α-halo ketones and α-halo acids, involving successive alkylation and condensation steps (Scheme 3) [17][18][19][20][21]. A convenient one-step synthesis of
Graphical Abstract
Figure 1: Structure of ritanserin and setoperone drugs.
Scheme 1: One-pot synthesis of 5(7)-oxothiazolopyrimidine-6-carbonitriles.
Scheme 2: Synthesis of thiazolopyrimidine-5-ones through the reaction of 2-aminothiazoles with ethyl acetoace...
Scheme 3: Synthesis of 2-(benzo[d]thiazol-2-yl)-2-(7-R-5-oxo-5H-thiazolo[3,2-a]pyrimidin-3-yl)acetonitriles.
Scheme 4: Synthesis of 3-acyl-7-methyl-5H-thiazolo[3,2-a]pyrimidin-5-ones.
Scheme 5: Sonogashira coupling reaction of 6-amino-2-thiouracil with propargyl bromide.
Scheme 6: Reactions of 6-substituted 2-thiouracils 1a,b with chloroethynylphosphonates 2a–c.
Scheme 7: Reaction of 5-methyl-2-thiouracil (1c) with chloroethynylphosphonates 2a–c.
Scheme 8: Reaction of 2-thiouracil (1d) with chloroethynylphosphonates 2a–c.
Scheme 9: Reaction of 6-trifluoromethyl-2-thiouracil (1e) with chloroethynylphosphonates 2a–c.
Scheme 10: A plausible mechanism of the reaction between 6-trifluoromethyl-2-thiouracil (1e) and chloroethynyl...
Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions
- Edgar Peris,
- Raúl Porcar,
- María Macia,
- Jesús Alcázar,
- Eduardo García-Verdugo and
- Santiago V. Luis
Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159
- mmol Cl/g,) was used as the starting material for the immobilization of N-arylimidazoles 2a and 2b, following the traditional alkylation protocol [18][19]. The preparation of these modified polymers was monitored by FT–ATR–IR, FT-Raman using a micro-spectroscopy accessory and the NBP test [20][21]. The
Graphical Abstract
Scheme 1: Synthesis of NHC-supported catalysts.
Scheme 2: Negishi benchmark reaction.
Figure 1: Negishi reaction catalyzed by immobilized NHC–Pd complexes. Conditions: methyl 4-bromobenzoate (0.2...
Scheme 3: Synthesis of immobilized NHC–Pd–RuPhos.
Figure 2: Negishi model reaction between 5 and 6 under flow conditions catalyzed by 4b. V = 0.535 mL, 363 mg ...
Figure 3: Negishi model reaction under flow conditions catalyzed by 8a. V = 2.9 mL, 1.25 g of catalyst, resid...
Figure 4: Negishi reaction between 5 and 6 catalyzed by 8a in the presence of SILLPs. a) Yield (%) vs time fo...
Figure 5: TEM images of the polymers after the Negishi reaction between 5 and 6. a) 8a, bar scale 20 nm, PdNP...
Scheme 4: Pd species immobilized onto SILLPs. i) 1 g SILLP 10, 100 mg PdCl2 in milli-Q® water (100 mL 1% HCl,...
Figure 6: Negishi reaction between 5 and 6 catalyzed by 11. 1 equiv methyl 4-bromobenzoate (6, 0.25 mmol), 2 ...
Figure 7: Negishi reaction between 5 and 6 under flow conditions catalyzed by 8a in the presence of a scaveng...
Figure 8: Effect of the structure of the SILLP scavenger for the Negishi reaction between 5 and 6 under flow ...
Figure 9: TEM images of the polymer after the Negishi reaction between 5 and 6 under flow conditions. a) 8a + ...
Design, synthesis and application of carbazole macrocycles in anion sensors
- Alo Rüütel,
- Ville Yrjänä,
- Sandip A. Kadam,
- Indrek Saar,
- Mihkel Ilisson,
- Astrid Darnell,
- Kristjan Haav,
- Tõiv Haljasorg,
- Lauri Toom,
- Johan Bobacka and
- Ivo Leito
Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157
- functional groups in the 3,6-positions of the carbazole. High lipophilicity is achievable by using alkylation and leads to the possibility of using the receptor dissolved in the lipophilic polymeric sensor membrane, without the need for chemical linking. Cyclization of the receptor is possible via the
- water (and possibly also in DMSO). Synthesis The general synthesis route is presented in Scheme 1. It was to some extent similar to the one that has previously been published by Sanchez et al. and Liu et al. [6][29] (see below). The synthetic route relied on the initial alkylation of the 3 and 6
- lead to acceptable results. Therefore, we decided to modify the reaction scheme. After alkylation, compound 2 was instead brominated, followed by amination of 4 leading to the desired diamino product 5a. Amine protection and subsequent coupling procedures, leading to 8, were the same as described in
Graphical Abstract
Figure 1: The biscarbazolylurea moiety.
Figure 2: The structure of the solid-contact ion-selective electrode (sensor): a) glassy carbon as the electr...
Figure 3: Studied receptor molecules.
Figure 4: MC001 and MC003 lowest energy conformers (COSMO-RS) showing intramolecular bonds. Color coding: whi...
Figure 5: a) Complex of MC008 with acetate; b) complex of MC006 with formate; c) complex of MC007 with lactat...
Scheme 1: The synthetic pathway to receptors CZ016 and MC001–MC014. The reaction yield for 2–3a/3b is given a...
Figure 6: Binding affinities of the studied receptors towards different carboxylates in DMSO-d6/H2O (99.5%:0....
Figure 7: Impedance spectra of sensors with each of the membranes. The spectra were recorded in 0.1 M sodium ...
Figure 8: Calibration curves for each of the membranes. The calibrations were performed by diluting 0.1 M sod...
Figure 9: The influence of solution pH on the potential responses of the sensor prototypes (three sensors for...
Figure 10: Potentiometric selectivity coefficients of interfering anions (relative to acetate) determined usin...
Stereoselective Biginelli-like reaction catalyzed by a chiral phosphoric acid bearing two hydroxy groups
- Xiaoyun Hu,
- Jianxin Guo,
- Cui Wang,
- Rui Zhang and
- Victor Borovkov
Beilstein J. Org. Chem. 2020, 16, 1875–1880, doi:10.3762/bjoc.16.155
- butanetetraol 1 is a parent compound of TADDOLs, which conventionally are obtained from enantiopure tartaric acids. The hydroxy group composition of 1 ensures its diverse reactivity. In 2010, our group established a convenient access [18] to 1 via a direct alkylation of diethyl tartrates by using PhMgBr
Graphical Abstract
Scheme 1: Synthesis of chiral phosphoric acid 3.
Scheme 2: Synthesis of methylated chiral phosphoric acid 7.
Scheme 3: Control experiment with catalyst 7.
Figure 1: A plausible chiral transition-state structure in the Biginelli-like reaction catalyzed by phosphori...
When metal-catalyzed C–H functionalization meets visible-light photocatalysis
- Lucas Guillemard and
- Joanna Wencel-Delord
Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147
- alkylation of arenes. The ruthenium-catalyzed meta-selective C–H functionalization through arene σ-activation was already well established yet limited by harsh reaction conditions and elevated reaction temperatures. Both research groups hence hypothesized that the Ru-metallacyclic intermediate, generated via
- very efficient at room temperature while applying blue LED irradiation. Two slightly modified catalytic systems composed of a [Ru(p-cymene)Cl2]2 catalyst and either K2CO3 or KOAc bases promoted the direct meta-selective C(sp2)–H alkylation with secondary and tertiary alkyl halides, delivering the
Graphical Abstract
Figure 1: Concept of dual synergistic catalysis.
Figure 2: Classification of catalytic systems involving two catalysts.
Figure 3: General mechanism for the dual nickel/photoredox catalytic system.
Figure 4: General mechanisms for C–H activation catalysis involving different reoxidation strategies.
Figure 5: Indole synthesis via dual C–H activation/photoredox catalysis.
Figure 6: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 7: Oxidative Heck reaction on arenes via the dual catalysis.
Figure 8: Proposed mechanism for the Heck reaction on arenes via dual catalysis.
Figure 9: Oxidative Heck reaction on phenols via the dual catalysis.
Figure 10: Proposed mechanism for the Heck reaction on phenols via dual catalysis.
Figure 11: Carbazole synthesis via dual C–H activation/photoredox catalysis.
Figure 12: Proposed mechanism for the carbazole synthesis via dual catalysis.
Figure 13: Carbonylation of enamides via the dual C–H activation/photoredox catalysis.
Figure 14: Proposed mechanism for carbonylation of enamides via dual catalysis.
Figure 15: Annulation of benzamides via the dual C–H activation/photoredox catalysis.
Figure 16: Proposed mechanism for the annulation of benzamides via dual catalysis.
Figure 17: Synthesis of indoles via the dual C–H activation/photoredox catalysis.
Figure 18: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 19: General concept of dual catalysis merging C–H activation and photoredox catalysis.
Figure 20: The first example of dual catalysis merging C–H activation and photoredox catalysis.
Figure 21: Proposed mechanism for the C–H arylation with diazonium salts via dual catalysis.
Figure 22: Dual catalysis merging C–H activation/photoredox using diaryliodonium salts.
Figure 23: Direct arylation via the dual catalytic system reported by Xu.
Figure 24: Direct arylation via dual catalytic system reported by Balaraman.
Figure 25: Direct arylation via dual catalytic system reported by Guo.
Figure 26: C(sp3)–H bond arylation via the dual Pd/photoredox catalytic system.
Figure 27: Acetanilide derivatives acylation via the dual C–H activation/photoredox catalysis.
Figure 28: Proposed mechanism for the C–H acylation with α-ketoacids via dual catalysis.
Figure 29: Acylation of azobenzenes via the dual catalysis C–H activation/photoredox.
Figure 30: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 31: Proposed mechanism for the C2-acylation of indoles with aldehydes via dual catalysis.
Figure 32: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 33: Perfluoroalkylation of arenes via the dual C–H activation/photoredox catalysis.
Figure 34: Proposed mechanism for perfluoroalkylation of arenes via dual catalysis.
Figure 35: Sulfonylation of 1-naphthylamides via the dual C–H activation/photoredox catalysis.
Figure 36: Proposed mechanism for sulfonylation of 1-naphthylamides via dual catalysis.
Figure 37: meta-C–H Alkylation of arenes via visible-light metallaphotocatalysis.
Figure 38: Alternative procedure for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 39: Proposed mechanism for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 40: C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 41: Proposed mechanism for C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 42: Undirected C–H aryl–aryl cross coupling via dual gold/photoredox catalysis.
Figure 43: Proposed mechanism for the undirected C–H aryl–aryl cross-coupling via dual catalysis.
Figure 44: Undirected C–H arylation of (hetero)arenes via dual manganese/photoredox catalysis.
Figure 45: Proposed mechanism for the undirected arylation of (hetero)arenes via dual catalysis.
Figure 46: Photoinduced C–H arylation of azoles via copper catalysis.
Figure 47: Photo-induced C–H chalcogenation of azoles via copper catalysis.
Figure 48: Decarboxylative C–H adamantylation of azoles via dual cobalt/photoredox catalysis.
Figure 49: Proposed mechanism for the C–H adamantylation of azoles via dual catalysis.
Figure 50: General mechanisms for the “classical” (left) and Cu-free variant (right) Sonogoshira reaction.
Figure 51: First example of a dual palladium/photoredox catalysis for Sonogashira-type couplings.
Figure 52: Arylation of terminal alkynes with diazonium salts via dual gold/photoredox catalysis.
Figure 53: Proposed mechanism for the arylation of terminal alkynes via dual catalysis.
Figure 54: C–H Alkylation of alcohols promoted by H-atom transfer (HAT).
Figure 55: Proposed mechanism for the C–H alkylation of alcohols promoted by HAT.
Figure 56: C(sp3)–H arylation of latent nucleophiles promoted by H-atom transfer.
Figure 57: Proposed mechanism for the C(sp3)–H arylation of latent nucleophiles promoted by HAT.
Figure 58: Direct α-arylation of alcohols promoted by H-atom transfer.
Figure 59: Proposed mechanism for the direct α-arylation of alcohols promoted by HAT.
Figure 60: C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 61: Proposed mechanism for the C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 62: C–H functionalization of nucleophiles via excited ketone/nickel dual catalysis.
Figure 63: Proposed mechanism for the C–H functionalization enabled by excited ketones.
Figure 64: Selective sp3–sp3 cross-coupling promoted by H-atom transfer.
Figure 65: Proposed mechanism for the selective sp3–sp3 cross-coupling promoted by HAT.
Figure 66: Direct C(sp3)–H acylation of amines via dual Ni/photoredox catalysis.
Figure 67: Proposed mechanism for the C–H acylation of amines via dual Ni/photoredox catalysis.
Figure 68: C–H hydroalkylation of internal alkynes via dual Ni/photoredox catalysis.
Figure 69: Proposed mechanism for the C–H hydroalkylation of internal alkynes.
Figure 70: Alternative procedure for the C–H hydroalkylation of ynones, ynoates, and ynamides.
Figure 71: Allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 72: Proposed mechanism for the allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 73: Asymmetric allylation of aldehydes via dual Cr/photoredox catalysis.
Figure 74: Proposed mechanism for the asymmetric allylation of aldehydes via dual catalysis.
Figure 75: Aldehyde C–H functionalization promoted by H-atom transfer.
Figure 76: Proposed mechanism for the C–H functionalization of aldehydes promoted by HAT.
Figure 77: Direct C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 78: Proposed mechanism for the C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 79: Direct C–H trifluoromethylation of strong aliphatic bonds promoted by HAT.
Figure 80: Proposed mechanism for the C–H trifluoromethylation of strong aliphatic bonds.
Et3N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties
- Dharmender Singh,
- Vipin Kumar and
- Virender Singh
Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146
- substituents at C1 (R4), compound 4eA with aromatic substituent exhibited better fluorescence due to extended conjugation. The effect of R2 substituent in these derivatives (4bA, 4dA, 4fA and 4gA) was also investigated and it was found that N-alkylation improved the photophysical properties along with higher
Graphical Abstract
Figure 1: Representative examples of some commercial drugs and biologically active alkaloids.
Scheme 1: Synthesis of β-carboline-linked 2-nitrochalcones.
Scheme 2: Synthesis of β-carboline-linked benzothiophenone frameworks.
Scheme 3: Comparison of outcome of one-pot vs two-pot approach.
Scheme 4: One-pot synthesis of β-carboline C-1-tethered benzothiophenone derivatives.
Scheme 5: One-pot synthesis of β-carboline C-3-linked benzothiophenone derivatives.
Scheme 6: One-pot synthesis of β-carboline-linked benzothiophene derivative 6C.
Scheme 7: Control experiment in the presence of a radical scavenger.
Figure 2: Proposed reaction mechanism.
Figure 3: Fluorescence spectra of 2aA–nA, 2bB, 2hB, and 6C.
Figure 4: Fluorescence spectra of 4aA–gA, and 4eB.
Pauson–Khand reaction of fluorinated compounds
- Jorge Escorihuela,
- Daniel M. Sedgwick,
- Alberto Llobat,
- Mercedes Medio-Simón,
- Pablo Barrio and
- Santos Fustero
Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138
- sulfonamides 47, followed by the introduction of the fluoroallyl group via N-alkylation with previously described mesylate 38 provided fluorinated enynes 48 (Scheme 24). The enantioenriched starting materials 48 were then evaluated in the Co-mediated PKR to yield the bicyclic products 49 in moderate to good
Graphical Abstract
Scheme 1: Schematic representation of the Pauson–Khand reaction.
Scheme 2: Substrates included in this review.
Scheme 3: Commonly accepted mechanism for the Pauson–Khand reaction.
Scheme 4: Regioselectivity of the PKR.
Scheme 5: Variability at the acetylenic and olefinic counterpart.
Scheme 6: Pauson–Khand reaction of fluoroolefinic enynes reported by the group of Ishizaki [46].
Scheme 7: PKR of enynes bearing fluorinated groups on the alkynyl moiety, reported by the group of Ishizaki [46]....
Scheme 8: Intramolecular PKR of 1,7-enynes reported by the group of Billard [47].
Scheme 9: Intramolecular PKR of 1,7-enynes reported by the group of Billard [48].
Scheme 10: Intramolecular PKR of 1,7-enynes by the group of Bonnet-Delpon [49]. Reaction conditions: i) Co(CO)8 (1...
Scheme 11: Intramolecular PKR of 1,6-enynes reported by the group of Ichikawa [50].
Scheme 12: Intramolecular Rh(I)-catalyzed PKR reported by the group of Hammond [52].
Scheme 13: Intramolecular PKR of allenynes reported by the group of Osipov [53].
Scheme 14: Intramolecular PKR of 1,7-enynes reported by the group of Osipov [53].
Scheme 15: Intramolecular PKR of fluorine-containing 1,6-enynes reported by the Konno group [54].
Scheme 16: Diastereoselective PKR with enantioenriched fluorinated enynes 34 [55].
Scheme 17: Intramolecular PKR reported by the group of Martinez-Solorio [56].
Scheme 18: Fluorine substitution at the olefinic counterpart.
Scheme 19: Synthesis of fluorinated enynes 37 [59].
Scheme 20: Fluorine-containing substrates in PKR [59].
Scheme 21: Pauson Khand reaction for fluorinated enynes by the Fustero group: scope and limitations [59].
Scheme 22: Synthesis of chloro and bromo analogues [59].
Scheme 23: Dimerization pathway [59].
Scheme 24: Synthesis of fluorine-containing N-tethered 1,7-enynes [61].
Scheme 25: Intramolecular PKR of chiral N-tethered fluorinated 1,7-enynes [61].
Scheme 26: Examples of further modifications to the Pauson−Khand adducts [61].
Scheme 27: Asymmetric synthesis the fluorinated enynes 53.
Scheme 28: Intramolecular PKR of chiral N-tethered 1,7-enynes 53 [64].
Scheme 29: Intramolecular PKR of chiral N-tethered 1,7-enyne bearing a vinyl fluoride [64].
Scheme 30: Catalytic intramolecular PKR of chiral N-tethered 1,7-enynes [64].
Scheme 31: Model fluorinated alkynes used by Riera and Fustero [70].
Scheme 32: PKR with norbornadiene and fluorinated alkynes 58 [71].
Scheme 33: Nucleophilic addition/detrifluoromethylation and retro Diels-Alder reactions [70].
Scheme 34: Tentative mechanism for the nucleophilic addition/retro-aldol reaction sequence.
Scheme 35: Catalytic PKR with norbornadiene [70].
Scheme 36: Scope of the PKR of trifluoromethylalkynes with norbornadiene [72].
Scheme 37: DBU-mediated detrifluoromethylation [72].
Scheme 38: A simple route to enone 67, a common intermediate in the total synthesis of α-cuparenone.
Scheme 39: Effect of the olefin partner in the regioselectivity of the PKR with trifluoromethyl alkynes [79].
Scheme 40: Intermolecular PKR of trifluoromethylalkynes with 2-norbornene reported by the group of Konno [54].
Scheme 41: Intermolecular PKR of diarylalkynes with 2-norbornene reported by the group of Helaja [80].
Scheme 42: Intermolecular PKR reported by León and Fernández [81].
Scheme 43: PKR reported with cyclopropene 73 [82].
Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach
- Rhys A. Lippa,
- John A. Murphy and
- Tim N. Barrett
Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134
- taking place (Scheme 8) [24][25][26]. The autoxidation of phosphonates under THF/potassium tert-butoxide has been reported previously [27]. In order to circumvent racemisation of aldehyde 22 during the Horner–Wadsworth–Emmons olefination, alkylation of phosphoramidate 13 was explored using commercially
- phosphoramidate protecting group, which was superior to the more commonly applied Boc protecting group which was unstable to the lithiation. This synthetic route replaces traditional Wittig and tandem alkylation/reduction methodologies, which suffer from complications arising from troublesome byproducts and
- formation of dimer 28. Conditions: KOt-Bu, THF, 1 h, 68% yield. Alkylation of phosphoramidate 13 by iodide 29 to afford compound 30 and byproducts alcohol 31 and dimer 32. Use of bromide 33 or tosylate 34 afforded only compounds 31 and 32. Conditions: (i) s-BuLi (1.3 equiv), iodide 29, THF, −78 °C, 30 min
Graphical Abstract
Figure 1: The Arg–Gly–Asp tripeptide sequence and examples of tetrahydro-1,8-naphthyridine-containing integri...
Scheme 1: Commonly used synthetic routes to tetrahydro-1,8-naphthyridine moieties by hydrogenation of saturat...
Scheme 2: Previous synthetic route to fluoropyrrolidine 6 utilising a Wittig reaction and the novel, higher y...
Scheme 3: Synthesis of phosphoramidate 9 from tetrahydro-1,8-naphthyridine 8. Conditions: s-BuLi (3 equiv), d...
Scheme 4: Mono- and diphosphorylation of tetrahydro-1,8-naphthyridine 11. Conditions: (i) s-BuLi (2 equiv), d...
Scheme 5: Synthesis of amine 6 from phosphonate 7 and aldehyde 5. Conditions: (i) T3P® (50% w/w in DCM, 3 equ...
Scheme 6: Monodeuteration of 13 as observed by 1H and 13C NMR. Conditions: s-BuLi (3 equiv), THF, −42 °C, 20 ...
Scheme 7: Sequential diphosphorylation of tetrahydronaphthyridine 11. Conditions: (i) iPrMgCl (1.5 equiv), TH...
Scheme 8: Possible mechanistic pathways for the formation of dimer 28. Conditions: KOt-Bu, THF, 1 h, 68% yiel...
Scheme 9: Alkylation of phosphoramidate 13 by iodide 29 to afford compound 30 and byproducts alcohol 31 and d...
Heterogeneous photocatalysis in flow chemical reactors
- Christopher G. Thomson,
- Ai-Lan Lee and
- Filipe Vilela
Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125
Graphical Abstract
Figure 1: A) Bar chart of the publications per year for the topics “Photocatalysis” (49,662 instances) and “P...
Figure 2: A) Professor Giacomo Ciamician and Dr. Paolo Silber on their roof laboratory at the University of B...
Scheme 1: PRC trifluoromethylation of N-methylpyrrole (1) using hazardous gaseous CF3I safely in a flow react...
Figure 3: A) Unit cells of the three most common crystal structures of TiO2: rutile, brookite, and anatase. R...
Figure 4: Illustration of the key semiconductor photocatalysis events: 1) A photon with a frequency exceeding...
Figure 5: Photocatalytic splitting of water by oxygen vacancies on a TiO2(110) surface. Reprinted with permis...
Figure 6: Proposed adsorption modes of A) benzene, B) chlorobenzene, C) toluene, D) phenol, E) anisole, and F...
Figure 7: Structures of the sulfonate-containing organic dyes RB5 (3) and MX-5B (4) and the adsorption isothe...
Figure 8: Idealised triclinic unit cell of a g-C3N4 type polymer, displaying possible hopping transport scena...
Figure 9: Idealised structure of a perfect g-C3N4 sheet. The central unit highlighted in red represents one t...
Figure 10: Timeline of the key processes of charge transport following the photoexcitation of g-C3N4, leading ...
Scheme 2: Photocatalytic bifunctionalisation of heteroarenes using mpg-C3N4, with the selected examples 5 and ...
Figure 11: A) Structure of four linear conjugated polymer photocatalysts for hydrogen evolution, displaying th...
Figure 12: Graphical representation of the common methods used to immobilise molecular photocatalysts (PC) ont...
Figure 13: Wireless light emitter-supported TiO2 (TiO2@WLE) HPCat spheres powered by resonant inductive coupli...
Figure 14: Graphical representation of zinc–perylene diimide (Zn-PDI) supramolecular assembly photocatalysis v...
Scheme 3: Upconversion of NIR photons to the UV frequency by NaYF4:Yb,Tm nanocrystals sequentially coated wit...
Figure 15: Types of reactors employed in heterogeneous photocatalysis in flow. A) Fixed bed reactors and the s...
Figure 16: Electrochemical potential of common semiconductor, transition metal, and organic dye-based photocat...
Scheme 4: Possible mechanisms of an immobilised molecular photoredox catalyst by oxidative or reductive quenc...
Scheme 5: Scheme of the CMB-C3N4 photocatalytic decarboxylative fluorination of aryloxyacetic acids, with the...
Scheme 6: Scheme of the g-C3N4 photocatalytic desilylative coupling reaction in flow and proposed mechanism [208].
Scheme 7: Proposed mechanism of the radical cyclisation of unsaturated alkyl 2-bromo-1,3-dicarbonyl compounds...
Scheme 8: N-alkylation of benzylamine and schematic of the TiO2-coated microfluidic device [213].
Scheme 9: Proposed mechanism of the Pt@TiO2 photocatalytic deaminitive cyclisation of ʟ-lysine (23) to ʟ-pipe...
Scheme 10: A) Proposed mechanism for the photocatalytic oxidation of phenylboronic acid (24). B) Photos and SE...
Scheme 11: Proposed mechanism for the DA-CMP3 photocatalytic aza-Henry reaction performed in a continuous flow...
Scheme 12: Proposed mechanism for the formation of the cyclic product 32 by TiO2-NC HPCats in a slurry flow re...
Scheme 13: Reaction scheme for the photocatalytic synthesis of homo and hetero disulfides in flow and scope of...
Scheme 14: Reaction scheme for the MoOx/TiO2 HPCat oxidation of cyclohexane (34) to benzene. The graph shows t...
Scheme 15: Proposed mechanism of the TiO2 HPC heteroarene C–H functionalisation via aryl radicals generated fr...
Scheme 16: Scheme of the oxidative coupling of benzylamines with the HOTT-HATN HPCat and selected examples of ...
Scheme 17: Photocatalysis oxidation of benzyl alcohol (40) to benzaldehyde (41) in a microflow reactor coated ...
Figure 17: Mechanisms of Dexter and Forster energy transfer.
Scheme 18: Continuous flow process for the isomerisation of alkenes with an ionic liquid-immobilised photocata...
Scheme 19: Singlet oxygen synthetic step in the total synthesis of canataxpropellane [265].
Scheme 20: Scheme and proposed mechanism of the singlet oxygen photosensitisation by CMP_X HPCats, with the st...
Scheme 21: Structures of CMP HPCat materials applied by Vilela and co-workers for the singlet oxygen photosens...
Scheme 22: Polyvinylchloride resin-supported TDCPP photosensitisers applied for singlet oxygen photosensitisat...
Scheme 23: Structure of the ionically immobilised TPP photosensitiser on amberlyst-15 ion exchange resins (TPP...
Scheme 24: Photosensitised singlet oxygen oxidation of citronellol (46) in scCO2, with automatic phase separat...
Scheme 25: Schematic of PS-Est-BDP-Cl2 being applied for singlet oxygen photosensitisation in flow. A) Pseudo-...
Scheme 26: Reaction scheme of the singlet oxygen oxidation of furoic acid (54) using a 3D-printed microfluidic...
Figure 18: A) Photocatalytic bactericidal mechanism by ROS oxidative cleavage of membrane lipids (R = H, amino...
Figure 19: A) Suggested mechanisms for the aqueous pollutant degradation by TiO2 in a slurry flow reactor [284-287]. B)...
Figure 20: Schematic of the flow system used for the degradation of aqueous oxytetracycline (56) solutions [215]. M...
Scheme 27: Degradation of a salicylic acid (57) solution by a coupled solar photoelectro-Fenton (SPEF) process...
Figure 21: A) Schematic flow diagram using the TiO2-coated NETmix microfluidic device for an efficient mass tr...
One-pot synthesis of 1,3,5-triazine-2,4-dithione derivatives via three-component reactions
- Gui-Feng Kang and
- Gang Zhang
Beilstein J. Org. Chem. 2020, 16, 1447–1455, doi:10.3762/bjoc.16.120
- and orthoformates and provided a rapid entry to a variety of 4-aryl-6-(alkylthio)-3,4-dihydro-1,3,5-triazine-2(1H)-thiones (29 examples). The synthetic strategy relies on the dual role of thiourea in the cyclization with the aldehydes and the alkylation via an intermediate imidate formation. The
- are versatile building blocks in organic synthesis, capable of constructing acyl derivatives [29][30][31][32][33] and ether derivatives [34][35][36] through acylation and alkylation under the appropriate conditions. In view of what was explained above, and as a result of our interest in developing
- alkylation, and/or due to the instability of the imines formed. In order to further explore the substrate scope of this multicomponent reaction, next we wanted to use other orthoformates. Interestingly, under the similar reaction conditions triethyl orthoformate (3b), tripropyl orthoformate (3c), and
Graphical Abstract
Figure 1: Selected examples of triazinethione-containing bioactive compounds.
Scheme 1: Strategies for the synthesis of triazinethiones.
Scheme 2: Aldehyde substrate scope of three-component reaction of aldehydes, thiourea and trimethyl orthoform...
Scheme 3: Orthoformate substrate scope of the three component reaction of benzaldehyde, thiourea, and orthofo...
Scheme 4: Gram-scale synthesis of 6aa.
Figure 2: X-ray structure of 6-(methylthio)-4-phenyl-3,4-dihydro-1,3,5-triazine-2(1H)-thione (6aa) with therm...
Scheme 5: Control experiments for investigation of the mechanism.
Scheme 6: Plausible mechanism.
The McKenna reaction – avoiding side reactions in phosphonate deprotection
- Katarzyna Justyna,
- Joanna Małolepsza,
- Damian Kusy,
- Waldemar Maniukiewicz and
- Katarzyna M. Błażewska
Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119
- for studying the possibility of an N-alkylation by alkyl bromide, formed during the silylation step. Finally, compound 13 was included to study the possibility of a chlorine for bromine exchange reaction. The phosphonocarboxylates 8 and 9 were used to explore whether the carboxyester group could be
- water and 1 equiv of TEA. Section 3: N-Alkylation As reported in the original paper [1], the McKenna reaction required up to 2 h at room temperature for simple phosphonates. However, depending on the structure of the phosphonate, longer reaction times are required, and the reaction is commonly carried
- the gas needed to be gently controlled to avoid BTMS removal from the reaction mixture. We encountered a different situation for compound 12. This substrate underwent N-alkylation under the McKenna reaction conditions only in the presence of Et3N, a commonly used additive for the protection of
Graphical Abstract
Scheme 1: Schematic overview of the McKenna reaction including the decomposition of BTMS in protic solvents. ...
Figure 1: The model compounds used for this study (in red: the functionality of the molecules vulnerable to s...
Scheme 2: Formation of the side products derived from 10. Conditions: An equimolar mixture of propargylamide ...
Scheme 3: Addition of HBr to compound 11.
Scheme 4: N-Alkylation of 9.
Scheme 5: N-Alkylation of 12.
Scheme 6: Exchange of the chlorine substituent with bromine in 2-chloro-N-phenethylacetamide (13) under McKen...
Recent synthesis of thietanes
- Jiaxi Xu
Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116
Graphical Abstract
Figure 1: Examples of biologically active thietane-containing molecules.
Figure 2: The diverse methods for the synthesis of thietanes.
Scheme 1: Synthesis of 1-(thietan-2-yl)ethan-1-ol (10) from 3,5-dichloropentan-2-ol (9).
Scheme 2: Synthesis of thietanose nucleosides 2,14 from 2,2-bis(bromomethyl)propane-1,3-diol (11).
Scheme 3: Synthesis of methyl 3-vinylthietane-3-carboxylate (19).
Scheme 4: Synthesis of 1,6-thiazaspiro[3.3]heptane (24).
Scheme 5: Synthesis of 6-amino-2-thiaspiro[3.3]heptane hydrochloride (28).
Scheme 6: Synthesis of optically active thietane 31 from vitamin C.
Scheme 7: Synthesis of an optically active thietane nucleoside from diethyl L-tartrate (32).
Scheme 8: Synthesis of thietane-containing spironucleoside 40 from 5-aldo-3-O-benzyl-1,2-O-isopropylidene-α-D...
Scheme 9: Synthesis of optically active 2-methylthietane-containing spironucleoside 43.
Scheme 10: Synthesis of a double-linked thietane-containing spironucleoside 48.
Scheme 11: Synthesis of two diastereomeric thietanose nucleosides via 2,4-di(benzyloxymethyl)thietane (49).
Scheme 12: Synthesis of the thietane-containing PI3k inhibitor candidate 54.
Scheme 13: Synthesis of the spirothietane 57 as the key intermediate to Nuphar sesquiterpene thioalkaloids.
Scheme 14: Synthesis of spirothietane 61 through a direct cyclic thioetherification of 3-mercaptopropan-1-ol.
Scheme 15: Synthesis of thietanes 66 from 1,3-diols 62.
Scheme 16: Synthesis of thietanylbenzimidazolone 75 from (iodomethyl)thiazolobenzimidazole 70.
Scheme 17: Synthesis of 2-oxa-6-thiaspiro[3.3]heptane (80) from bis(chloromethyl)oxetane 76 and thiourea.
Scheme 18: Synthesis of the thietane-containing glycoside, 2-O-p-toluenesulfonyl-4,6-thioanhydro-α-D-gulopyran...
Scheme 19: Synthesis of methyl 4,6-thioanhydro-α-D-glucopyranoside (89).
Scheme 20: Synthesis of thietane-fused α-D-galactopyranoside 93.
Scheme 21: Synthesis of thietane-fused α-D-gulopyranoside 100.
Scheme 22: Synthesis of 3,5-anhydro-3-thiopentofuranosides 104.
Scheme 23: Synthesis of anhydro-thiohexofuranosides 110, 112 and 113 from from 1,2:4,5-di-O-isopropylidene D-f...
Scheme 24: Synthesis of optically active thietanose nucleosides from D- and L-xyloses.
Scheme 25: Synthesis of thietane-fused nucleosides.
Scheme 26: Synthesis of 3,5-anhydro-3-thiopentofuranosides.
Scheme 27: Synthesis of 2-amino-3,5-anhydro-3-thiofuranoside 141.
Scheme 28: Synthesis of thietane-3-ols 145 from (1-chloromethyl)oxiranes 142 and hydrogen sulfide.
Scheme 29: Synthesis of thietane-3-ol 145a from chloromethyloxirane (142a).
Scheme 30: Synthesis of thietane-3-ols 145 from 2-(1-haloalkyl)oxiranes 142 and 147 with ammonium monothiocarb...
Scheme 31: Synthesis of 7-deoxy-5(20)thiapaclitaxel 154a, a thietane derivative of taxoids.
Scheme 32: Synthesis of 5(20)-thiadocetaxel 158 from 10-deacetylbaccatin III (155).
Scheme 33: Synthesis of thietane derivatives 162 as precursors for deoxythiataxoid synthesis through oxiraneme...
Scheme 34: Synthesis of 7-deoxy 5(20)-thiadocetaxel 154b.
Scheme 35: Mechanism for the formation of the thietane ring in 171 from oxiranes with vicinal leaving groups 1...
Scheme 36: Synthesis of cis-2,3-disubstituted thietane 175 from thiirane-2-methanol 172.
Scheme 37: Synthesis of a bridged thietane 183 from aziridine cyclohexyl tosylate 179 and ammonium tetrathiomo...
Scheme 38: Synthesis of thietanes via the photochemical [2 + 2] cycloaddition of thiobenzophenone 184a with va...
Scheme 39: Synthesis of spirothietanes through the photo [2 + 2] cycloaddition of cyclic thiocarbonyls with ol...
Scheme 40: Photochemical synthesis of spirothietane-thioxanthenes 210 from thioxanthenethione (208) and butatr...
Scheme 41: Synthesis of thietanes 213 from 2,4,6-tri(tert-butyl)thiobenzaldehyde (211) with substituted allene...
Scheme 42: Photochemical synthesis of spirothietanes 216 and 217 from N-methylthiophthalimide (214) with olefi...
Scheme 43: Synthesis of fused thietanes from quadricyclane with thiocarbonyl derivatives 219.
Scheme 44: Synthesis of tricyclic thietanes via the photo [2 + 2] cycloaddition of N-methyldithiosuccinimides ...
Scheme 45: Synthesis of tricyclic thietanes via the photo [2 + 2] cycloaddition of N-methylthiosuccinimide/thi...
Scheme 46: Synthesis of tricyclic thietanes via the photo [2 + 2] cycloaddition of N-alkylmonothiophthalimides...
Scheme 47: Synthesis of spirothietanes from dithiosuccinimides 223 with 2,3-dimethyl-2-butene (215a).
Scheme 48: Synthesis of thietanes 248a,b from diaryl thione 184b and ketene acetals 247a,b.
Scheme 49: Photocycloadditions of acridine-9-thiones 249 and pyridine-4(1H)-thione (250) with 2-methylacrynitr...
Scheme 50: Synthesis of thietanes via the photo [2 + 2] cycloaddition of mono-, di-, and trithiobarbiturates 2...
Scheme 51: Synthesis of spirothietanes via the photo [2 + 2] cycloaddition of 1,1,3-trimethyl-2-thioxo-1,2-dih...
Scheme 52: Synthesis of spirothietanes via the photo [2 + 2] cycloaddition of thiocoumarin 286 with olefins.
Scheme 53: Photochemical synthesis of thietanes 296–299 from semicyclic and acyclic thioimides 292–295 and 2,3...
Scheme 54: Photochemical synthesis of spirothietane 301 from 1,3,3-trimethylindoline-2-thione (300) and isobut...
Scheme 55: Synthesis of spirobenzoxazolethietanes 303 via the photo [2 + 2] cycloaddition of alkyl and aryl 2-...
Scheme 56: Synthesis of spirothietanes from tetrahydrothioxoisoquinolines 306 and 307 with olefins.
Scheme 57: Synthesis of spirothietanes from 1,3-dihydroisobenzofuran-1-thiones 311 and benzothiophene-1-thione...
Scheme 58: Synthesis of 2-triphenylsilylthietanes from phenyl triphenylsilyl thioketone (316) with electron-po...
Scheme 59: Diastereoselective synthesis of spiropyrrolidinonethietanes 320 via the photo [2 + 2] cycloaddition...
Scheme 60: Synthesis of bicyclic thietane 323 via the photo [2 + 2] cycloaddition of 2,4-dioxo-3,4-dihydropyri...
Scheme 61: Photo-induced synthesis of fused thietane-2-thiones 325 and 326 from silacyclopentadiene 324 and ca...
Scheme 62: Synthesis of highly strained tricyclic thietanes 328 via the intramolecular photo [2 + 2] cycloaddi...
Scheme 63: Synthesis of tri- and pentacyclic thietanes 330 and 332, respectively, through the intramolecular p...
Scheme 64: Synthesis of tricyclic thietanes 334 via the intramolecular photo [2 + 2] cycloaddition of N-vinylt...
Scheme 65: Synthesis of tricyclic thietanes 336 via the intramolecular photo [2 + 2] cycloaddition of N-but-3-...
Scheme 66: Synthesis of tricyclic thietanes via the intramolecular photo [2 + 2] cycloaddition of N-but-3-enyl...
Scheme 67: Synthesis of tetracyclic thietane 344 through the intramolecular photo [2 + 2] cycloaddition of N-[...
Scheme 68: Synthesis of tri- and tetracyclic thietanes 348, 350, and 351, through the intramolecular photo [2 ...
Scheme 69: Synthesis of tetracyclic fused thietane 354 via the photo [2 + 2] cycloaddition of vinyl 2-thioxo-3H...
Scheme 70: Synthesis of highly rigid thietane-fused β-lactams via the intramolecular photo [2 + 2] cycloadditi...
Scheme 71: Asymmetric synthesis of a highly rigid thietane-fused β-lactam 356a via the intramolecular photo [2...
Scheme 72: Diastereoselective synthesis of the thietane-fused β-lactams via the intramolecular photo [2 + 2] c...
Scheme 73: Asymmetric synthesis of thietane-fused β-lactams 356 via the intramolecular photo [2 + 2] cycloaddi...
Scheme 74: Synthesis of the bridged bis(trifluoromethyl)thietane from 2,2,4,4-tetrakis(trifluoromethyl)-1,3-di...
Scheme 75: Synthesis of the bridged-difluorothietane 368 from 2,2,4,4-tetrafluoro-1,3-dithietane (367) and qua...
Scheme 76: Synthesis of bis(trifluoromethyl)thietanes from 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (3...
Scheme 77: Synthesis of 2,2-dimethylthio-4,4-di(trifluoromethyl)thietane (378) from 2,2,4,4-tetrakis(trifluoro...
Scheme 78: Formation of bis(trifluoromethyl)thioacetone (381) through nucleophilic attack of dithietane 363 by...
Scheme 79: Synthesis of 2,2-bis(trifluoromethyl)thietanes from 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietan...
Scheme 80: Synthesis of the bridged bis(trifluoromethyl)thietane 364 from of 2,2,4,4-tetrakis(trifluoromethyl)...
Scheme 81: Synthesis of 2,4-diiminothietanes 390 from alkenimines and 4-methylbenzenesulfonyl isothiocyanate (...
Scheme 82: Synthesis of arylidene 2,4-diiminothietanes 393 starting from phosphonium ylides 391 and isothiocya...
Scheme 83: Synthesis of thietane-2-ylideneacetates 397 through a DABCO-catalyzed formal [2 + 2] cycloaddition ...
Scheme 84: Synthesis of 3-substituted thietanes 400 from (1-chloroalkyl)thiiranes 398.
Scheme 85: Synthesis of N-(thietane-3-yl)azaheterocycles 403 and 404 through reaction of chloromethylthiirane (...
Scheme 86: Synthesis of 3-sulfonamidothietanes 406 from sulfonamides and chloromethylthiirane (398a).
Scheme 87: Synthesis of N-(thietane-3-yl)isatins 408 from chloromethylthiirane (398a) and isatins 407.
Scheme 88: Synthesis of 3-(nitrophenyloxy)thietanes 410 from nitrophenols 409 and chloromethylthiirane (398a).
Scheme 89: Synthesis of N-aryl-N-(thietane-3-yl)cyanamides 412 from N-arylcyanamides 411 and chloromethylthiir...
Scheme 90: Synthesis of 1-(thietane-3-yl)pyrimidin-2,4(1H,3H)-diones 414 from chloromethylthiirane (398a) and ...
Scheme 91: Synthesis of 2,4-diiminothietanes 418 from 2-iminothiiranes 416 and isocyanoalkanes 415.
Scheme 92: Synthesis of 2-vinylthietanes 421 from thiiranes 419 and 3-chloroallyl lithium (420).
Scheme 93: Synthesis of thietanes from thiiranes 419 and trimethyloxosulfonium iodide 424.
Scheme 94: Mechanism for synthesis of thietanes 425 from thiiranes 419 and trimethyloxosulfonium iodide 424.
Scheme 95: Synthesis of functionalized thietanes from thiiranes and dimethylsulfonium acylmethylides.
Scheme 96: Mechanism for the rhodium-catalyzed synthesis of functionalized thietanes 429 from thiiranes 419 an...
Scheme 97: Synthesis of 3-iminothietanes 440 through thermal isomerization from 4,5-dihydro-1,3-oxazole-4-spir...
Scheme 98: Synthesis of thietanes 443 from 3-chloro-2-methylthiolane (441) through ring contraction.
Scheme 99: Synthesis of an optically active thietanose 447 from D-xylose involving a ring contraction.
Scheme 100: Synthesis of optically thietane 447 via the DAST-mediated ring contraction of 448.
Scheme 101: Synthesis of the optically thietane nucleoside 451 via the ring contraction of thiopentose in 450.
Scheme 102: Synthesis of spirothietane 456 from 3,3,5,5-tetramethylthiolane-2,4-dithione (452) and benzyne (453...
Scheme 103: Synthesis of thietanes 461 via photoisomerization of 2H,6H-thiin-3-ones 459.
Scheme 104: Phosphorodithioate-mediated synthesis of 1,4-diarylthietanes 465.
Scheme 105: Mechanism of the phosphorodithioate-mediated synthesis of 1,4-diarylthietanes 465.
Scheme 106: Phosphorodithioate-mediated synthesis of trisubstituted thietanes (±)-470.
Scheme 107: Mechanism on the phosphorodithioate-mediated synthesis of trisubstituted thietanes.
Scheme 108: Phosphorodithioate-mediated synthesis of thietanes (±)-475.
Scheme 109: Phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes from aldehydes 476 and acrylon...
Scheme 110: Phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes via a one-pot three-component ...
Scheme 111: Mechanism for the phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes via three-co...
Scheme 112: Phosphorodithioate-mediated synthesis of substituted 3-nitrothietanes.
Scheme 113: Mechanism on the phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes (±)-486.
Scheme 114: Asymmetric synthesis of (S)-2-phenylthietane (497).
Scheme 115: Asymmetric synthesis of optically active 2,4-diarylthietanes.
Scheme 116: Synthesis of 3-acetamidothietan-2-one 503 via the intramolecular thioesterification of 3-mercaptoal...
Scheme 117: Synthesis of 4-substituted thietan-2-one via the intramolecular thioesterification of 3-mercaptoalk...
Scheme 118: Synthesis of 4,4-disubstituted thietan-2-one 511 via the intramolecular thioesterification of the 3...
Scheme 119: Synthesis of a spirothietan-2-one 514 via the intramolecular thioesterification of 3-mercaptoalkano...
Scheme 120: Synthesis of thiatetrahydrolipstatin starting from (S)-(−)-epichlorohydrin ((S)-142a).
Scheme 121: Synthesis of 2-phenethyl-4-(propan-2-ylidene)thietane (520) from 5-bromo-6-methyl-1-phenylhept-5-en...
Scheme 122: Synthesis of 2-phenethyl-4-(propan-2-ylidene)thietane (520) directly from S-(5-bromo-6-methyl-1-phe...
Scheme 123: Synthesis of 2-alkylidenethietanes from S-(2-bromoalk-1-en-4-yl)thioacetates.
Scheme 124: Synthesis of 2-alkylidenethietanes from S-(2-bromo/chloroalk-1-en-4-yl)thiols.
Scheme 125: Synthesis of spirothietan-3-ol 548 from enone 545 and ammonium hydrosulfide.
Scheme 126: Asymmetric synthesis of the optically active thietanoside from cis-but-2-ene-1,4-diol (47).
Scheme 127: Synthesis of 2-alkylidenethietan-3-ols 557 via the fluoride-mediated cyclization of thioacylsilanes ...
Scheme 128: Synthesis of 2-iminothietanes via the reaction of propargylbenzene (558) and isothiocyanates 560 in...
Scheme 129: Synthesis of 2-benzylidenethietane 567 via the nickel complex-catalyzed electroreductive cyclizatio...
Scheme 130: Synthesis of 2-iminothietanes 569 via the photo-assisted electrocyclic reaction of N-monosubstitute...
Scheme 131: Synthesis of ethyl 3,4-diiminothietane-2-carboxylates from ethyl thioglycolate (570) and bis(imidoy...
Scheme 132: Synthesis of N-(thietan-3-yl)-α-oxoazaheterocycles from azaheterocyclethiones and chloromethyloxira...
Scheme 133: Synthesis of thietan-3-yl benzoate (590) via the nickel-catalyzed intramolecular reductive thiolati...
Scheme 134: Synthesis of 2,2-bis(trifluoromethyl)thietane from 3,3-bis(trifluoromethyl)-1,2-dithiolane.
Scheme 135: Synthesis of thietanes from enamines and sulfonyl chlorides.
Scheme 136: Synthesis of spirothietane 603 via the [2 + 3] cycloaddition of 2,2,4,4-tetramethylcyclobutane-1,3-...
Scheme 137: Synthesis of thietane (605) from 1-bromo-3-chloropropane and sulfur.
Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis
- Stephanie G. E. Amos,
- Marion Garreau,
- Luca Buzzetti and
- Jerome Waser
Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103
- reported a visible light-promoted photochemical reductive decarboxylation/alkylation of carboxylic acid analogs (Scheme 4) [45]. In this protocol, the carboxylic acids are converted into the corresponding RAE 4.1 by a condensation with N-hydroxyphthalimide. The organic dye eosin Y (OD13, E(PC/PC−) ≈ −1.1 V
- ), in the presence of the sacrificial electron donor DIPEA, can reduce these species under green light irradiation. The ensuing decarboxylation provides a C(sp3) radical, which undergoes a radical conjugate addition with a suitable Michael acceptor 4.2, providing the desired alkylation products 4.3. A
- protocol for the radical alkylation of imines using ammonium alkylbis(catecholato)silicates 5.4 as the C(sp3) radical precursors (Scheme 5b) [50]. 4CzIPN (OD6) was found again to be the best organic photocatalyst, triggering the oxidative fragmentation of the bis(catecholato)silicate. The so-formed alkyl
Graphical Abstract
Figure 1: Selected examples of organic dyes. Mes-Acr+: 9-mesityl-10-methylacridinium, DCA: 9,10-dicyanoanthra...
Scheme 1: Activation modes in photocatalysis.
Scheme 2: Main strategies for the formation of C(sp3) radicals used in organophotocatalysis.
Scheme 3: Illustrative example for the photocatalytic oxidative generation of radicals from carboxylic acids:...
Scheme 4: Illustrative example for the photocatalytic reductive generation of C(sp3) radicals from redoxactiv...
Figure 2: Common substrates for the photocatalytic oxidative generation of C(sp3) radicals.
Scheme 5: Illustrative example for the photocatalytic oxidative generation of radicals from dihydropyridines ...
Scheme 6: Illustrative example for the photocatalytic oxidative generation of C(sp3) radicals from trifluorob...
Scheme 7: Illustrative example for the photocatalytic reductive generation of C(sp3) radicals from benzylic h...
Scheme 8: Illustrative example for the photocatalytic generation of C(sp3) radicals via direct HAT: the cross...
Scheme 9: Illustrative example for the photocatalytic generation of C(sp3) radicals via indirect HAT: the deu...
Scheme 10: Selected precursors for the generation of aryl radicals using organophotocatalysis.
Scheme 11: Illustrative example for the photocatalytic reductive generation of aryl radicals from aryl diazoni...
Scheme 12: Illustrative examples for the photocatalytic reductive generation of aryl radicals from haloarenes:...
Scheme 13: Illustrative example for the photocatalytic reductive generation of aryl radicals from aryl halides...
Scheme 14: Illustrative example for the photocatalytic reductive generation of aryl radicals from arylsulfonyl...
Scheme 15: Illustrative example for the reductive photocatalytic generation of aryl radicals from triaryl sulf...
Scheme 16: Main strategies towards acyl radicals used in organophotocatalysis.
Scheme 17: Illustrative example for the decarboxylative photocatalytic generation of acyl radicals from α-keto...
Scheme 18: Illustrative example for the oxidative photocatalytic generation of acyl radicals from acyl silanes...
Scheme 19: Illustrative example for the oxidative photocatalytic generation of carbamoyl radicals from 4-carba...
Scheme 20: Illustrative example of the photocatalytic HAT approach for the generation of acyl radicals from al...
Scheme 21: General reactivity of a) radical cations; b) radical anions; c) the main strategies towards aryl an...
Scheme 22: Illustrative example for the oxidative photocatalytic generation of alkene radical cations from alk...
Scheme 23: Illustrative example for the reductive photocatalytic generation of an alkene radical anion from al...
Figure 3: Structure of C–X radical anions and their neutral derivatives.
Scheme 24: Illustrative example for the photocatalytic reduction of imines and the generation of an α-amino C(...
Scheme 25: Illustrative example for the oxidative photocatalytic generation of aryl radical cations from arene...
Scheme 26: NCR classifications and generation.
Scheme 27: Illustrative example for the photocatalytic reductive generation of iminyl radicals from O-aryl oxi...
Scheme 28: Illustrative example for the photocatalytic oxidative generation of iminyl radicals from α-N-oxy ac...
Scheme 29: Illustrative example for the photocatalytic oxidative generation of iminyl radicals via an N–H bond...
Scheme 30: Illustrative example for the photocatalytic oxidative generation of amidyl radicals from Weinreb am...
Scheme 31: Illustrative example for the photocatalytic reductive generation of amidyl radicals from hydroxylam...
Scheme 32: Illustrative example for the photocatalytic reductive generation of amidyl radicals from N-aminopyr...
Scheme 33: Illustrative example for the photocatalytic oxidative generation of amidyl radicals from α-amido-ox...
Scheme 34: Illustrative example for the photocatalytic oxidative generation of aminium radicals: the N-aryltet...
Scheme 35: Illustrative example for the photocatalytic oxidative generation of nitrogen-centered radical catio...
Scheme 36: Illustrative example for the photocatalytic oxidative generation of nitrogen-centered radical catio...
Scheme 37: Illustrative example for the photocatalytic oxidative generation of hydrazonyl radical from hydrazo...
Scheme 38: Generation of O-radicals.
Scheme 39: Illustrative examples for the photocatalytic generation of O-radicals from N-alkoxypyridinium salts...
Scheme 40: Illustrative examples for the photocatalytic generation of O-radicals from alkyl hydroperoxides: th...
Scheme 41: Illustrative example for the oxidative photocatalytic generation of thiyl radicals from thiols: the...
Scheme 42: Main strategies and reagents for the generation of sulfonyl radicals used in organophotocatalysis.
Scheme 43: Illustrative example for the reductive photocatalytic generation of sulfonyl radicals from arylsulf...
Scheme 44: Illustrative example of a Cl atom abstraction strategy for the photocatalytic generation of sulfamo...
Scheme 45: Illustrative example for the oxidative photocatalytic generation of sulfonyl radicals from sulfinic...
Scheme 46: Illustrative example for the photocatalytic generation of electronically excited triplet states: th...
Scheme 47: Illustrative example for the photocatalytic generation of electronically excited triplet states: th...
Fluorinated phenylalanines: synthesis and pharmaceutical applications
- Laila F. Awad and
- Mohammed Salah Ayoup
Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91
- synthesized by alkylation of 26a,b with the chiral auxiliary 31, which was obtained by reaction of the cyclic dipeptide 30 with triethyloxonium tetrafluoroborate. The alkylation reaction of 26a,b was carried out with n-BuLi in THF at −78 °C to give 32a,b. Acid hydrolysis of the alkylated product 32a,b
- afforded the ethyl esters of tetrafluorophenylalanine 33a,b, which by alkaline hydrolysis afforded the tetrafluoro derivatives 29a and 29b, respectively [43] (Scheme 7). The syntheses of (R)-38a and (R)-38b were carried out by alkylation of the Schöllkopf reagent ((2S)-(+)-2,5-dihydro-3,6-dimethoxy-2
- -isopropylpyrazine, 34) with the corresponding fluorinated benzyl bromides 35a,b via intermediates 36a,b. The alkylation products were then hydrolyzed to generate the amino acid esters which were directly Boc protected to give the N-Boc-protected amino acid methyl esters 37a,b. Finally, ester hydrolysis afforded the
Graphical Abstract
Figure 1: Categories I–V of fluorinated phenylalanines.
Scheme 1: Synthesis of fluorinated phenylalanines via Jackson’s method.
Scheme 2: Synthesis of all-cis-tetrafluorocyclohexylphenylalanines.
Scheme 3: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine (nPt: neopentyl, TCE: trichloroethyl).
Scheme 4: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine derivatives 17.
Scheme 5: Synthesis of fluorinated Phe analogues from Cbz-protected aminomalonates.
Scheme 6: Synthesis of tetrafluorophenylalanine analogues via the 3-methyl-4-imidazolidinone auxiliary 25.
Scheme 7: Synthesis of tetrafluoro-Phe derivatives via chiral auxiliary 31.
Scheme 8: Synthesis of 2,5-difluoro-Phe and 2,4,5-trifluoro-Phe via Schöllkopf reagent 34.
Scheme 9: Synthesis of 2-fluoro- and 2,6-difluoro Fmoc-Phe derivatives starting from chiral auxiliary 39.
Scheme 10: Synthesis of 2-[18F]FPhe via chiral auxiliary 43.
Scheme 11: Synthesis of FPhe 49a via photooxidative cyanation.
Scheme 12: Synthesis of FPhe derivatives via Erlenmeyer azalactone synthesis.
Scheme 13: Synthesis of (R)- and (S)-2,5-difluoro Phe via the azalactone method.
Scheme 14: Synthesis of 3-bromo-4-fluoro-(S)-Phe (65).
Scheme 15: Synthesis of [18F]FPhe via radiofluorination of phenylalanine with [18F]F2 or [18F]AcOF.
Scheme 16: Synthesis of 4-borono-2-[18F]FPhe.
Scheme 17: Synthesis of protected 4-[18F]FPhe via arylstannane derivatives.
Scheme 18: Synthesis of FPhe derivatives via intermediate imine formation.
Scheme 19: Synthesis of FPhe derivatives via Knoevenagel condensation.
Scheme 20: Synthesis of FPhe derivatives 88a,b from aspartic acid derivatives.
Scheme 21: Synthesis of 2-(2-fluoroethyl)phenylalanine derivatives 93 and 95.
Scheme 22: Synthesis of FPhe derivatives via Zn2+ complexes.
Scheme 23: Synthesis of FPhe derivatives via Ni2+ complexes.
Scheme 24: Synthesis of 3,4,5-trifluorophenylalanine hydrochloride (109).
Scheme 25: Synthesis of FPhe derivatives via phenylalanine aminomutase (PAM).
Scheme 26: Synthesis of (R)-2,5-difluorophenylalanine 115.
Scheme 27: Synthesis of β-fluorophenylalanine via 2-amino-1,3-diol derivatives.
Scheme 28: Synthesis of β-fluorophenylalanine derivatives via the oxazolidinone chiral auxiliary 122.
Scheme 29: Synthesis of β-fluorophenylalanine from pyruvate hemiketal 130.
Scheme 30: Synthesis of β-fluorophenylalanine (136) via fluorination of β-hydroxyphenylalanine (137).
Scheme 31: Synthesis of β-fluorophenylalanine from aziridine derivatives.
Scheme 32: Synthesis of β-fluorophenylalanine 136 via direct fluorination of pyruvate esters.
Scheme 33: Synthesis of β-fluorophenylalanine via fluorination of ethyl 3-phenylpyruvate enol using DAST.
Scheme 34: Synthesis of β-fluorophenylalanine derivatives using photosensitizer TCB.
Scheme 35: Synthesis of β-fluorophenylalanine derivatives using Selectflour and dibenzosuberenone.
Scheme 36: Synthesis of protected β-fluorophenylalanine via aziridinium intermediate 150.
Scheme 37: Synthesis of β-fluorophenylalanine derivatives via fluorination of α-hydroxy-β-aminophenylalanine d...
Scheme 38: Synthesis of β-fluorophenylalanine derivatives from α- or β-hydroxy esters 152a and 155.
Scheme 39: Synthesis of a series of β-fluoro-Phe derivatives via Pd-catalyzed direct fluorination of β-methyle...
Scheme 40: Synthesis of series of β-fluorinated Phe derivatives using quinoline-based ligand 162 in the Pd-cat...
Scheme 41: Synthesis of β,β-difluorophenylalanine derivatives from 2,2-difluoroacetaldehyde derivatives 164a,b....
Scheme 42: Synthesis of β,β-difluorophenylalanine derivatives via an imine chiral auxiliary.
Scheme 43: Synthesis of α-fluorophenylalanine derivatives via direct fluorination of protected Phe 174.
Figure 2: Structures of PET radiotracers of 18FPhe derivatives.
Figure 3: Structures of melfufen (179) and melphalan (180) anticancer drugs.
Figure 4: Structure of gastrazole (JB95008, 181), a CCK2 receptor antagonist.
Figure 5: Dual CCK1/CCK2 antagonist 182.
Figure 6: Structure of sitagliptin (183), an antidiabetic drug.
Figure 7: Structure of retaglpitin (184) and antidiabetic drug.
Figure 8: Structure of evogliptin (185), an antidiabetic drug.
Figure 9: Structure of LY2497282 (186) a DPP-4 inhibitor for the treatment of type II diabetes.
Figure 10: Structure of ulimorelin (187).
Figure 11: Structure of GLP1R (188).
Figure 12: Structures of Nav1.7 blockers 189 and 190.
Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents
- Yafei Guo and
- Syuzanna R. Harutyunyan
Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90
- lead to versatile chiral building blocks, such as a β-alkyl-substituted aldehyde (66% yield, 94:6 er) or a β-bromo-γ-alkyl-substituted alcohol (71% yield, 93:7 er). The asymmetric allylic alkylation (AAA) is a very useful method that allows the enantioselective formation of C–C bonds, and copper
Graphical Abstract
Scheme 1: Copper-catalysed ACA of organometallics to piperidones. A) addition of organozinc reagents; B) addi...
Scheme 2: Copper-catalysed ACA of alkenylalanes to N-substituted-2,3-dehydro-4-piperidones.
Scheme 3: Copper-catalysed asymmetric addition of dialkylzinc reagents to N-acyl-4-methoxypyridinium salts fo...
Scheme 4: Copper-catalysed ACA of organozirconium reagents to N-substituted 2,3-dehydro-4-piperidones and lac...
Scheme 5: Copper-catalysed ACA of Grignard reagents to chromones and coumarins and further derivatisation of ...
Scheme 6: Copper-catalysed ACA of Grignard reagents to N-protected quinolones.
Scheme 7: Copper-catalysed ACAs of organometallics to conjugated unsaturated lactams.
Scheme 8: Copper-catalysed ACA of Et2Zn to 5,6-dihydro-2-pyranone.
Scheme 9: Copper-catalysed ACA of Grignard reagents to pyranone and 5,6-dihydro-2-pyranone.
Scheme 10: Copper-catalysed AAA of an organozirconium reagent to heterocyclic acceptors.
Scheme 11: Copper-catalysed ring opening of an oxygen-bridged substrate with trialkylaluminium reagents.
Scheme 12: Copper-catalysed ring opening of oxabicyclic substrates with organolithium reagents (selected examp...
Scheme 13: Copper-catalysed ring opening of polycyclic meso hydrazines.
Scheme 14: Copper-catalysed ACA of Grignard reagents to alkenyl-substituted aromatic N-heterocycles.
Scheme 15: Copper-catalysed ACA of Grignard reagents to β-substituted alkenylpyridines.
Scheme 16: Copper-catalysed ACA of organozinc reagents to alkylidene Meldrum’s acids.
Aryl-substituted acridanes as hosts for TADF-based OLEDs
- Naveen Masimukku,
- Dalius Gudeika,
- Oleksandr Bezvikonnyi,
- Ihor Syvorotka,
- Rasa Keruckiene,
- Dmytro Volyniuk and
- Juozas V. Grazulevicius
Beilstein J. Org. Chem. 2020, 16, 989–1000, doi:10.3762/bjoc.16.88
- according to the reported procedure [28]. The subsequent alkylation of 1 using bromoethane afforded the N-ethylated dibromo compound 2 in 80% yield. The target compounds 3–6 were then obtained by Suzuki cross-coupling reactions between brominated acridan 2 and the respective phenylboronic acids in the
Graphical Abstract
Scheme 1: Synthesis of acridan-based compounds 3–6. Reagents and conditions: (a) bromoethane, KOH, tetrabutyl...
Figure 1: Theoretically calculated HOMO and LUMO levels distributions and optimized geometries of 3–6 DFT cal...
Figure 2: DSC curves of compounds 4 and 5.
Figure 3: Absorption and PL spectra (λex = 330 nm) of compounds 3–6. a) Absorption spectra as neat films, dil...
Figure 4: a) Cyclic voltammogram of derivative 3 in dichloromethane (a three-electrode cell consisting of a p...
Figure 5: TOF photocurrent transients for holes in vacuum-deposited layers of compound 4 (a); hole mobility v...
Figure 6: Energy diagrams of the fabricated OLEDs (a); normalized electroluminescence spectra of devices A–C ...
Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches
- Rodrigo Costa e Silva,
- Luely Oliveira da Silva,
- Aloisio de Andrade Bartolomeu,
- Timothy John Brocksom and
- Kleber Thiago de Oliveira
Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83
- formation started in 2016 with the report from Gryko’s group on the photoredox α-alkylation of aldehydes with diazo compounds using 1 mol % of TPP or ZnTPP as photocatalyst [10] (Scheme 1), thus obtaining functionalized aldehydes in 47–90% yields. These results are similar to those previously reported by
- excited state potentials, including porphyrin derivatives. Adapted from [10][12][22]. Electronic configurations of the species of oxygen. Adapted from [66]. Photoredox alkylation of aldehydes with diazo acetates using porphyrins and a Ru complex. aUsing a loading of 0.1 mol % for ZnTPP. Proposed mechanism
- for the alkylation of aldehydes with diazo acetates in the presence of TPP. Arylation of heteroarenes with aryldiazonium salts using TPFPP as photocatalyst, and corresponding mechanism. A) Scope with different aryldiazonium salts and enol acetates. B) Photocatalytic cycles and comparison between TPP
Graphical Abstract
Figure 1: Chemical structures of the porphyrinoids and their absorption spectra: in bold are highlighted the ...
Figure 2: Photophysical and photochemical processes (Por = porphyrin). Adapted from [12,18].
Figure 3: Main dual photocatalysts and their oxidative/reductive excited state potentials, including porphyri...
Scheme 1: Photoredox alkylation of aldehydes with diazo acetates using porphyrins and a Ru complex. aUsing a ...
Scheme 2: Proposed mechanism for the alkylation of aldehydes with diazo acetates in the presence of TPP.
Scheme 3: Arylation of heteroarenes with aryldiazonium salts using TPFPP as photocatalyst, and corresponding ...
Scheme 4: A) Scope with different aryldiazonium salts and enol acetates. B) Photocatalytic cycles and compari...
Scheme 5: Photoarylation of isopropenyl acetate A) Comparison between batch and continuous-flow approaches an...
Scheme 6: Dehalogenation induced by red light using thiaporphyrin (STPP).
Scheme 7: Applications of NiTPP as both photoreductant and photooxidant.
Scheme 8: Proposed mechanism for obtaining tetrahydroquinolines by reductive quenching.
Scheme 9: Selenylation and thiolation of anilines.
Scheme 10: NiTPP as photoredox catalyst in oxidative and reductive quenching, in comparison with other photoca...
Scheme 11: C–O bond cleavage of 1-phenylethanol using a cobalt porphyrin (CoTMPP) under visible light.
Scheme 12: Hydration of terminal alkynes by RhIII(TSPP) under visible light irradiation.
Scheme 13: Regioselective photocatalytic hydro-defluorination of perfluoroarenes by RhIII(TSPP).
Scheme 14: Formation of 2-methyl-2,3-dihydrobenzofuran by intramolecular hydro-functionalization of allylpheno...
Scheme 15: Photocatalytic oxidative hydroxylation of arylboronic acids using UNLPF-12 as heterogeneous photoca...
Scheme 16: Photocatalytic oxidative hydroxylation of arylboronic acids using MOF-525 as heterogeneous photocat...
Scheme 17: Preparation of the heterogeneous photocatalyst CNH.
Scheme 18: Photoinduced sulfonation of alkenes with sulfinic acid using CNH as photocatalyst.
Scheme 19: Sulfonic acid scope of the sulfonation reactions.
Scheme 20: Regioselective sulfonation reaction of arimistane.
Scheme 21: Synthesis of quinazolin-4-(3H)-ones.
Scheme 22: Selective photooxidation of aromatic benzyl alcohols to benzaldehydes using Pt/PCN-224(Zn).
Scheme 23: Photooxidation of benzaldehydes to benzoic acids using Pt or Pd porphyrins.
Scheme 24: Photocatalytic reduction of various nitroaromatics using a Ni-MOF.
Scheme 25: Photoinduced cycloadditions of CO2 with epoxides by MOF1.
Figure 4: Electronic configurations of the species of oxygen. Adapted from [66].
Scheme 26: TPP-photocatalyzed generation of 1O2 and its application in organic synthesis. Adapted from [67-69].
Scheme 27: Pericyclic reactions involving singlet oxygen and their mechanisms. Adapted from [67].
Scheme 28: First scaled up ascaridole preparation from α-terpinene.
Scheme 29: Antimalarial drug synthesis using an endoperoxidation approach.
Scheme 30: Photooxygenation of colchicine.
Scheme 31: Synthesis of (−)-pinocarvone from abundant (+)-α-pinene.
Scheme 32: Seeberger’s semi-synthesis of artemisinin.
Scheme 33: Synthesis of artemisinin using TPP and supercritical CO2.
Scheme 34: Synthesis of artemisinin using chlorophyll a.
Scheme 35: Quercitol stereoisomer preparation.
Scheme 36: Photocatalyzed preparation of naphthoquinones.
Scheme 37: Continuous endoperoxidation of conjugated dienes and subsequent rearrangements leading to oxidized ...
Scheme 38: The Opatz group total synthesis of (–)-oxycodone.
Scheme 39: Biomimetic syntheses of rhodonoids A, B, E, and F.
Scheme 40: α-Photooxygenation of chiral aldehydes.
Scheme 41: Asymmetric photooxidation of indanone β-keto esters by singlet oxygen using PTC as a chiral inducer...
Scheme 42: Asymmetric photooxidation of both β-keto esters and β-keto amides by singlet oxygen using PTC-2 as ...
Scheme 43: Bifunctional photo-organocatalyst used for the asymmetric oxidation of β-keto esters and β-keto ami...
Scheme 44: Mechanism of singlet oxygen oxidation of sulfides to sulfoxides.
Scheme 45: Controlled oxidation of sulfides to sulfoxides using protonated porphyrins as photocatalysts. aIsol...
Scheme 46: Photochemical oxidation of sulfides to sulfoxides using PdTPFPP as photocatalyst.
Scheme 47: Controlled oxidation of sulfides to sulfoxides using SnPor@PAF as a photosensitizer.
Scheme 48: Syntheses of 2D-PdPor-COF and 3D-Pd-COF.
Scheme 49: Photocatalytic oxidation of A) thioanisole to methyl phenyl sulfoxide and B) various aryl sulfides,...
Scheme 50: General mechanism for oxidation of amines to imines.
Scheme 51: Oxidation of secondary amines to imines.
Scheme 52: Oxidation of secondary amines using Pd-TPFPP as photocatalyst.
Scheme 53: Oxidative amine coupling using UNLPF-12 as heterogeneous photocatalyst.
Scheme 54: Synthesis of Por-COF-1 and Por-COF-2.
Scheme 55: Photocatalytic oxidation of amines to imines by Por-COF-2.
Scheme 56: Photocyanation of primary amines.
Scheme 57: Synthesis of ᴅ,ʟ-tert-leucine hydrochloride.
Scheme 58: Photocyanation of catharanthine and 16-O-acetylvindoline using TPP.
Scheme 59: Photochemical α-functionalization of N-aryltetrahydroisoquinolines using Pd-TPFPP as photocatalyst.
Scheme 60: Ugi-type reaction with 1,2,3,4-tetrahydroisoquinoline using molecular oxygen and TPP.
Scheme 61: Ugi-type reaction with dibenzylamines using molecular oxygen and TPP.
Scheme 62: Mannich-type reaction of tertiary amines using PdTPFPP as photocatalyst.
Scheme 63: Oxidative Mannich reaction using UNLPF-12 as heterogeneous photocatalyst.
Scheme 64: Transformation of amines to α-cyanoepoxides and the proposed mechanism.
Diversity-oriented synthesis of 17-spirosteroids
- Benjamin Laroche,
- Thomas Bouvarel,
- Martin Louis-Sylvestre and
- Bastien Nay
Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79
- derivatives of several steroidal skeletons, starting from available 17-ethynyl-17-hydroxysteroid compounds 1–3 (Scheme 2). Alkylation of the alcohol function proceeded well under classical conditions (NaH then RCH2Br in DMF), either in the presence of allyl bromide or of 4-pentenyl bromide. Mestranol (1
- ), lynestrenol (2) and desogestrel (3) gave alkylated products 5–7 in good yields and were readily engaged in the RCEYM reaction. The RCEYM reaction was then undertaken post alkylation. In fact, these quaternary propargyl ethers are particularly hindered. For such hindered substrates, we previously employed the
- engaged in biological screening campaign in the near future. Experimental General procedure A for alkylation of 17-ethynyl-17-hydroxysteroids To a suspension of 17-ethynyl-17-hydroxysteroids (1 mmol) in dry DMF (10 mL), NaH (2 mmol, used as a 60% stabilized mixture in oil) was added at 0 °C. After
Graphical Abstract
Scheme 1: Two diversity-oriented strategies: (a) Diversity installed during the construction of the skeleton;...
Figure 1: Structure of four 17-ethynyl-17-hydroxysteroids 1–4 (top) and how they could be used to generate di...
Scheme 2: Synthesis of spirocyclic steroid derivatives by the RCEYM reaction. Conditions: (a) NaH (2 equiv), ...
Figure 2: Structure of metathesis catalysts.
Scheme 3: One-pot RCEYM/Diels–Alder reaction strategy applied to the mestranol and lynestrenol cores. Notes: a...
Figure 3: Rationale for the observed stereochemistry: (a) NOESY correlations observed on compound 16b, showin...
Aldehydes as powerful initiators for photochemical transformations
- Maria A. Theodoropoulou,
- Nikolaos F. Nikitas and
- Christoforos G. Kokotos
Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76
- reported a selective photoredox merger C(sp3)–H alkylation/arylation of ethers using benzaldehyde as the photoorganocatalyst and nickel as the transition metal catalyst [57]. For the coupling between (3-bromopropyl)benzene (132) and THF (131), presented in Scheme 28, NiBr2·glyme (134) was employed as the
- methodology, affording the products 143 and 145a–d in good yield. The N-substituted pyrrolidines 144a/d–g were also compatible, providing the desired products in good yields, except from the N-acetyl (144e) and N-pivaloylpyrrolidines (144f), for which the yields dropped considerably. The alkylation of the
- the photoredox merger reaction. Proposed mechanism for the C(sp3)–H alkylation/arylation of ethers. Substrate scope for the photochemical alkylation of ethers. C(sp3)–H Functionalization of N-containing molecules. Substrate scope for the photochemical alkylation of N-containing molecules. Additional
Graphical Abstract
Scheme 1: Norrish type I and II dissociations.
Scheme 2: Proposed radical pair formation after the photolysis of benzaldehyde (8).
Scheme 3: Aldehydes in the Paterno–Büchi reaction.
Scheme 4: 2,3-Diazabicyclo[2.2.1]hept-2-ene (DBH).
Scheme 5: Dissociation pathways of benzaldehyde.
Scheme 6: Reactions that lead to polarized products detectable by CIDNP.
Scheme 7: MMA (26), DEABP (27), and Michler’s ketone (28).
Scheme 8: Radical intermediates of DEABP.
Scheme 9: Photoinitiated polymerization of monomeric MMA (26) using the quinoxalines 32 and benzaldehyde (8).
Scheme 10: Acetone (4) and formaldehyde (35) as photografting initiators.
Scheme 11: Photografting by employing acetaldehyde (36) as the photoinitiator.
Scheme 12: Proposed photolysis mechanism for aliphatic ketones 44 and formaldehyde (35).
Scheme 13: Initiator 50, reductant 51, and benzaldehyde derivatives 52–54 for the polymerization of the methac...
Scheme 14: Proposed mechanism of the photomediated atom transfer radical polymerization employing the benzalde...
Scheme 15: cis/trans isomerization employing triplet states of photosensitizers.
Scheme 16: Salicylaldehyde (68) forms an internal hydrogen bond.
Scheme 17: Olefin isomerization via energy transfer from a carbonyl compound.
Scheme 18: Mechanistic pathways for the Paterno–Büchi reaction.
Scheme 19: Isomeric oxetanes formed after photochemical addition of aryl aldehydes to 2-butenes.
Scheme 20: Rotation of the C3–C4 bond of the biradical intermediate may lead to all four conformations.
Scheme 21: Photolysis products of benzaldehyde (8) in different solvents. a) In benzene or ethanol. b) In hex-...
Scheme 22: N-tert-Butylbenzamide formation proceeds via a benzoyl radical.
Scheme 23: Photochemical pinacol coupling.
Scheme 24: Photochemical ATRA catalyzed by 4-anisaldehyde (52).
Scheme 25: Proposed triplet sensitization mechanism of the ATRA reaction in the presence of 4-anisaldehyde (52...
Scheme 26: Benzaldehyde-mediated photoredox CDC reaction: compatible amides and ethers.
Scheme 27: Photoredox cross-dehydrogenative coupling (CDC) conditions and proposed reaction mechanism.
Scheme 28: Optimized conditions for the photoredox merger reaction.
Scheme 29: Proposed mechanism for the C(sp3)–H alkylation/arylation of ethers.
Scheme 30: Substrate scope for the photochemical alkylation of ethers.
Scheme 31: C(sp3)–H Functionalization of N-containing molecules.
Scheme 32: Substrate scope for the photochemical alkylation of N-containing molecules.
Scheme 33: Additional products yielded by the photochemical alkylation reaction of N-containing molecules.
Scheme 34: C(sp3)–H functionalization of thioethers.
Scheme 35: Proposed mechanism for the C(sp3)–H alkylation/arylation of N-containing molecules and thioethers.
Scheme 36: Hydroacylation using 4-cyanobenzaldehyde (53) as the photoinitiator.
Scheme 37: Selectivity for the formation of the α,α-disubstituted aldehydes.
Scheme 38: Substrate scope for the photochemical addition of aldehydes to Michael acceptors.
Scheme 39: Proposed mechanism for the hydroacylation of Michael acceptors using 4-cyanobenzaldehyde (53) as th...
Scheme 40: Catalytic arylation of aromatic aldehydes by aryl bromides in which the reaction product acts as th...
Scheme 41: Proposed mechanism for the catalytic arylation of benzaldehydes by aryl bromides in which the react...
Scheme 42: Functionalization of the chiral cyclobutanes 180.
Scheme 43: Optimized reaction conditions and proposed mechanism for the sulfonylcyanation of cyclobutenes.
Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts
- David Schönbauer,
- Carlo Sambiagio,
- Timothy Noël and
- Michael Schnürch
Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74
- interest [27]. In our continuing quest to develop methods for the introduction of pure hydrocarbon residues avoiding volatile reagents [28][29], our attention was drawn to stable N-alkyl-(2,4,6-triphenyl)pyridinium salts (Katritzky salts) as alkylation reagents in the context of non-directed C–H
- borylations [41][42], heteroarylations [43], and thioesterifications [44]. Additionally, several methods using photoredox chemistry were also published. For instance, the alkylation of isoquinolines under iridium catalysis and alkynylation with eosin Y as the catalyst [45][46]. In this contribution, we
- . Conclusion In summary, we developed a photoredox-catalyzed C(sp³)–H alkylation of N-aryltetrahydroisoquinolines under mild conditions. Easily accessible and bench-stable pyridinium salts were used as precursors for the required alkyl radicals. The transformation gives good to moderate yields using benzyl and
Graphical Abstract
Scheme 1: Examples of photocatalytic C–C bond formation by nucleophilic trapping of a reactive THIQ intermedi...
Figure 1: Kinetic profile for the benzylation of 1 to 3.
Scheme 2: Benzylation of N-phenyl-THIQ.
Scheme 3: Benzylation of substituted N-arylTHIQs.
Scheme 4: Removal of the PMP protecting group.
Scheme 5: Alkylation of N-phenyl-THIQ derivatives. Conditions: a2 mol % [Ir(dtbbpy)(ppy)2]PF6, DMA, 60 h; b2 ...
Scheme 6: Proposed mechanism.
Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K2CO3/n-Bu4PBr in water
- Thanigaimalai Pillaiyar,
- Masoud Sedaghati and
- Gregor Schnakenburg
Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71
- at the position 3 of indoles [1][2][3][4]. Friedel–Crafts alkylation of (1H-indol-3-yl)methanols with indoles has proven to be a powerful strategy for the preparation of biologically important 3,3′-diindolylmethanes (DIMs) [5][6][7][8][9][10][11][12][13][14]. Additionally, (1H-indol-3-yl)methanols
- cycle. 3-Indolylmethanols are versatile pre-electrophiles for C–C functionalization at the 3-position of indoles. Particularly, the Friedel–Crafts alkylation of 3-indolylmethanols with indoles has become a useful method for the preparation of 3,3'-, and 3,6'-DIMs, which are known to possess a wide
- protocol for the preparation of trifluoromethyl(indolyl)phenylmethanols, which are of significant interest serving as pre-electrophiles for C–C functionalization at the 3-position of indoles. Particularly, the Friedel–Crafts alkylation of 3-indolylmethanols with indoles has become a useful method for the
Graphical Abstract
Figure 1: Structures of trifluoromethylated compounds and their biological activities.
Figure 2: Synthetic approaches toward hydroxyalkylation of indole.
Figure 3: Structures of heterocycles that did not react with ketone 2a.
Scheme 1: Gram-scale synthesis of 2,2,2-trifluoro-1-(1H-indol-3-yl)-1-phenylethan-1-ols (3a and 3p).
Figure 4: Recyclability of the catalytic system n-Bu4PBr/K2CO3 for the preparation of 2,2,2-trifluoro-1-(5-me...
Scheme 2: Synthesis of trifluoromethylated unsymmetrical 3,3'- and 3,6'-DIMs (9–11).
Scheme 3: Proposed mechanism for the preparation of 3a as an example.
Scheme 4: Control experiments.
Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules
- Valerian Dragutan,
- Ileana Dragutan,
- Albert Demonceau and
- Lionel Delaude
Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68
- -metal-catalyzed transformations were needed to achieve the total synthesis of des-epoxy-amphidinolide N, including a palladium asymmetric allylic alkylation (Pd-AAA), a Mukaiyama aldol reaction (with Sn), and a Krische allylation (with Ir) [72]. As special feature of this procedure, an Evans aldol
Graphical Abstract
Scheme 1: Intramolecular (A) and intermolecular (B) enyne metathesis reactions.
Scheme 2: Ene–yne and yne–ene mechanisms for intramolecular enyne metathesis reactions.
Scheme 3: Metallacarbene mechanism in intermolecular enyne metathesis.
Scheme 4: The Oguri strategy for accessing artemisinin analogs 1a–c through enyne metathesis.
Scheme 5: Access to the tetracyclic core of nanolobatolide (2) via tandem enyne metathesis followed by an Eu(...
Scheme 6: Synthesis of (−)-amphidinolide E (3) using an intermolecular enyne metathesis as the key step.
Scheme 7: Synthesis of amphidinolide K (4) by an enyne metathesis route.
Scheme 8: Trost synthesis of des-epoxy-amphidinolide N (5) [72].
Scheme 9: Enyne metathesis between the propargylic derivative and the allylic alcohol in the synthesis of the...
Scheme 10: Synthetic route to amphidinolide N (6a).
Scheme 11: Synthesis of the stereoisomeric precursors of amphidinolide V (7a and 7b) through alkyne ring-closi...
Scheme 12: Synthesis of the anthramycin precursor 8 from ʟ-methionine by a tandem enyne metathesis–cross metat...
Scheme 13: Synthesis of (−)‐clavukerin A (9) and (−)‐isoclavukerin A (10) by an enyne metathesis route startin...
Scheme 14: Synthesis of (−)-isoguaiene (11) through an enyne metathesis as the key step.
Scheme 15: Synthesis of erogorgiaene (12) by a tandem enyne metathesis/cross metathesis sequence using the sec...
Scheme 16: Synthesis of (−)-galanthamine (13) from isovanilin by an enyne metathesis.
Scheme 17: Application of enyne metathesis for the synthesis of kempene diterpenes 14a–c.
Scheme 18: Synthesis of the alkaloid (+)-lycoflexine (15) through enyne metathesis.
Scheme 19: Synthesis of the AB subunits of manzamine A (16a) and E (16b) by enyne metathesis.
Scheme 20: Jung's synthesis of rhodexin A (17) by enyne metathesis/cross metathesis reactions.
Scheme 21: Total synthesis of (−)-flueggine A (18) and (+)-virosaine B (19) from Weinreb amide by enyne metath...
Scheme 22: Access to virgidivarine (20) and virgiboidine (21) by an enyne metathesis route.
Scheme 23: Enyne metathesis approach to (−)-zenkequinone B (22).
Scheme 24: Access to C-aryl glycoside 23 by an intermolecular enyne metathesis/Diels–Alder cycloaddition.
Scheme 25: Synthesis of spiro-C-aryl glycoside 24 by a tandem intramolecular enyne metathesis/Diels–Alder reac...
Scheme 26: Pathways to (−)-exiguolide (25) by Trost’s Ru-catalyzed enyne cross-coupling and cross-metathesis [94].
Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons
- Goki Hirata,
- Yu Yamane,
- Naoya Tsubaki,
- Reina Hara and
- Takashi Nishikata
Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45
- addition (ATRA) [21] (Scheme 1, i–iii). Therefore, we postulated that if we could control the reactivities of the alkynyl–Cu and ATRA adducts, a tandem tertiary alkylation followed by an alkynylation could occur to produce a 1,3-enyne possessing a quaternary carbon center with good regio- and
- methodology can realize a Pd-free catalyst system to prepare complex quaternary carbon atoms. Herein, we report the Cu-catalyzed control of the reactivity of an alkyne (addition and coupling) undergoing tandem tertiary alkylation and alkynylation to produce a 1,3-enyne containing a quaternary carbon center
- Pd-catalyzed cascade reaction (C–C bond formation/C–H cyclization process) of N-arylpropynamide 4 for the preparation of indolinone derivatives 5 was previously reported by Li’s group [34][35]. In another report on C–H cyclization by Lei’s group, Ni-catalyzed aromatic C–H alkylation occurs via a
Graphical Abstract
Scheme 1: Reaction modes of alkyne.
Figure 1: Substrate scope of 1 and 2. aConducted at 80 °C for 24 h in MeCN with CuBr (10 mol %), 1,10-Phen (2...
Scheme 2: Proposed mechanism.
Scheme 3: Control experiment.
Scheme 4: Reaction of 2a and 4a.
Figure 2: Substrate scope of 2 and 4. aConducted at 100 °C for 20 h in 1,4-dioxane with CuI (10 mol %), 1,10-...
