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Search for "iridium catalyst" in Full Text gives 23 result(s) in Beilstein Journal of Organic Chemistry.
Synthetic approach to borrelidin fragments: focus on key intermediates
- Yudhi Dwi Kurniawan,
- Zetryana Puteri Tachrim,
- Teni Ernawati,
- Faris Hermawan,
- Ima Nurasiyah and
- Muhammad Alfin Sulmantara
Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91
- . Starting from ent-52, obtained via the asymmetric hydrogenation of 51 using the catalyst (Sa)-50, the previously developed three-steps reaction sequence was adopted and repeated three times, yielding polydeoxypropionic acid 57 in an overall yield of 54%. The iridium catalyst (Ra)-50 was chosen to ensure
Graphical Abstract
Figure 1: Chemical structure of borrelidin (1).
Scheme 1: Synthetic strategy for Morken’s C2–C12 intermediate 20 as reported by Uguen et al. [41].
Scheme 2: Preparation of monoacetates 37 and ent-38 by Uguen et al. [41].
Scheme 3: Preparation of sulfones 27 and ent-27 by Uguen et al. [41].
Scheme 4: Attempts to couple sulfones 27 and ent-27 with epoxides 23a–c reported by Uguen et al. [41].
Scheme 5: Modified synthetic plan for Morken’s C2–C12 intermediate by Uguen [41].
Scheme 6: Revised synthetic strategy for Morken’s C2–C12 intermediate 20 by Uguen [41].
Scheme 7: Iterative synthesis of polydeoxypropionates developed by Zhou et al. [40].
Scheme 8: Application of iterative synthesis of polydeoxypropionate to construct the C3–C11 fragment 60 of bo...
Scheme 9: Retrosynthetic analysis of borrelidin by Yadav et al. [39].
Scheme 10: Two-carbon homologation of precursor 66 in the synthesize C1–C11 fragment 61 of borrelidin [39].
Scheme 11: Synthesis of the C1–C11 fragment 61 of borrelidin from monoalcohol 65 [39].
Scheme 12: Synthetic plan for Theodorakis’ C3–C11 fragment 82 of borrelidin by Laschat et al. [38].
Scheme 13: Synthesis of Theodorakis’ C3–C11 fragment 82 from compound 88 [38].
Scheme 14: Retrosynthesis of 61 and 62b by Minnaard and Madduri [37].
Scheme 15: Synthesis of intermediate 98 by Minnaard and Madduri [37].
Scheme 16: Synthesis of Ōmura’s C1–C11 fragment 61 by Minnaard and Madduri [37].
Scheme 17: Synthesis of fragment 62b of borrelidin as proposed by Minnaard and Madduri [37].
Scheme 18: Iterative directed allylation for the synthesis of deoxypropionates by Herber and Breit [33].
Scheme 19: Iterative copper-mediated directed allyl substitution for the synthesis of Theodorakis’ C3–C11 frag...
Scheme 20: Retrosynthesis of the C3–C17 fragment of borrelidin by Iqbal and co-workers [35].
Scheme 21: Synthesis of key intermediates 137 and 147 for the synthesis of the C3–C17 fragment of borrelidin.
Scheme 22: Synthesis of the C3–C17 fragment 150a,b of borrelidin.
Scheme 23: Synthesis of the C11–C15 fragment 155a of borrelidin.
Scheme 24: Macrocyclization of borrelidin model compounds 155a and 155b using ring-closing metathesis.
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
- which resulted in C3-alkylated pyridines 51. Based on the reactions performed for the catalytic activity of the silyl-iridium complex, the authors proposed a catalytic mechanism (Scheme 11b). The mechanism involves the initial formation of the active silyl-iridium catalyst A which through oxidative
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.
Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series
- Cécile Alleman,
- Charlène Gadais,
- Laurent Legentil and
- François-Hugues Porée
Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23
- formation of the fused cyclobutane acid 162 as the desired precursor for the cyclooctane formation. The ring expansion was achieved in the presence of an iridium catalyst and under blue LED irradiation, via the trapping by TEMPO or O2 of the cyclobutyl radical resulting from decarboxylation, which allowed a
Graphical Abstract
Figure 1: Examples of terpenes containing a bicyclo[3.6.0]undecane motif.
Figure 2: Commercially available first and second generation Grubbs and Hoveyda–Grubbs catalysts.
Figure 3: Examples of strategies to access the fusicoccan and ophiobolin tricyclic core structure by RCM.
Scheme 1: Synthesis of bicyclic core structure 12 of ophiobolin M (13) and cycloaraneosene (14).
Scheme 2: Synthesis of the core structure 21 of ophiobolins and fusicoccanes.
Scheme 3: Ring-closing metathesis attempts starting from thioester 22.
Scheme 4: Total synthesis of ent-fusicoauritone (28).
Figure 4: General structure of ophiobolins and congeners.
Scheme 5: Total synthesis of (+)-ophiobolin A (8).
Scheme 6: Investigation of RCM for the synthesis of ophiobolin A (8). Path A) RCM with TBDPS-protected alcoho...
Scheme 7: Synthesis of the core structure of cotylenin A aglycon, cotylenol (50).
Scheme 8: Synthesis of tricyclic core structure of fusicoccans.
Scheme 9: Total synthesis of (−)-teubrevin G (59).
Scheme 10: Synthesis of the core skeleton 63 of the basmane family.
Scheme 11: Total synthesis of (±)-schindilactone A (68).
Scheme 12: Total synthesis of dactylol (72).
Scheme 13: Ring-closing metathesis for the total synthesis of (±)-asteriscanolide (2).
Scheme 14: Synthesis of the simplified skeleton of pleuromutilin (1).
Scheme 15: Total synthesis of (−)-nitidasin (93) using a ring-closing metathesis to construct the eight-member...
Scheme 16: Total synthesis of (±)-naupliolide (97).
Scheme 17: Synthesis of the A-B ring structure of fusicoccane (101).
Scheme 18: First attempts of TRCM of dienyne substrates.
Scheme 19: TRCM on optimized substrates towards the synthesis of ophiobolin A (8).
Scheme 20: Tandem ring-closing metathesis for the synthesis of variecolin intermediates 114 and 115.
Scheme 21: Synthesis of poitediol (118) using the allylsilane ring-closing metathesis.
Scheme 22: Access to scaffold 122 by a NHK coupling reaction.
Scheme 23: Key step to construct the [5-8] bicyclooctanone core of aquatolide (4).
Scheme 24: Initial strategy to access aquatolide (4).
Scheme 25: Synthetic plan to cotylenin A (130).
Scheme 26: [5-8] Bicyclic structure of brachialactone (7) constructed by a Mizoroki–Heck reaction.
Scheme 27: Influence of the replacement of the allylic alcohol moiety.
Scheme 28: Formation of variecolin intermediate 140 through a SmI2-mediated Barbier-type reaction.
Scheme 29: SmI2-mediated ketyl addition. Pleuromutilin (1) eight-membered ring closure via C5–C14 bond formati...
Scheme 30: SmI2-mediated dialdehyde cyclization cascade of [5-8-6] pleuromutilin scaffold 149.
Scheme 31: A) Modular synthetic route to mutilin and pleuromutilin family members by Herzon’s group. B) Scaffo...
Scheme 32: Photocatalyzed oxidative ring expansion in pleuromutilin (1) total synthesis.
Scheme 33: Reductive radical cascade cyclization route towards (−)-6-epi-ophiobolin N (168).
Scheme 34: Reductive radical cascade cyclization route towards (+)-6-epi-ophiobolin A (173).
Scheme 35: Radical 8-endo-trig-cyclization of a xanthate precursor.
Figure 5: Structural representations of hypoestin A (177), albolic acid (178), and ceroplastol II (179) beari...
Scheme 36: Synthesis of the common [5-8-5] tricyclic intermediate of hypoestin A (177), albolic acid (178), an...
Scheme 37: Asymmetric synthesis of hypoestin A (177), albolic acid (178), and ceroplastol II (179).
Figure 6: Scope of the Pauson–Khand reaction.
Scheme 38: Nazarov cyclization revealing the fusicoauritone core structure 192.
Scheme 39: Synthesis of fusicoauritone (28) through Nazarov cyclization.
Scheme 40: (+)-Epoxydictymene (5) synthesis through a Nicholas cyclization followed by a Pauson–Khand reaction...
Scheme 41: Synthesis of aquatolide (4) by a Mukaiyama-type aldolisation.
Scheme 42: Tandem Wolff/Cope rearrangement furnishing the A-B bicyclic moiety 204 of variecolin.
Scheme 43: Asymmetric synthesis of the A-B bicyclic core 205 and 206 of variecolin.
Scheme 44: Formation of [5-8]-fused rings by cyclization under thermal activation.
Scheme 45: Construction of the [5-8-6] tricyclic core structure of variecolin (3) by Diels–Alder reaction.
Scheme 46: Synthesis of the [6-4-8-5]-tetracyclic skeleton by palladium-mediated cyclization.
Scheme 47: Access to the [5-8] bicyclic core structure of asteriscanolide (227) through rhodium-catalyzed cycl...
Scheme 48: Total syntheses of asterisca-3(15),6-diene (230) and asteriscanolide (2) with a Rh-catalyzed cycliz...
Scheme 49: Photocyclization of 2-pyridones to access the [5-8-5] backbone of fusicoccanes.
Scheme 50: Total synthesis of (+)-asteriscunolide D (245) and (+)-aquatolide (4) through photocyclization.
Scheme 51: Biocatalysis pathway to construct the [5-8-5] tricyclic scaffold of brassicicenes.
Scheme 52: Influence of the CotB2 mutant over the cyclization’s outcome of GGDP.
Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study
- Angel Ho,
- Austin Pounder,
- Krish Valluru,
- Leanne D. Chen and
- William Tam
Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30
- electron-withdrawing groups inactivates the iridium catalyst, perhaps by chelation with the carbonyl and the bridging oxygen atom. Computational Computational details All density functional theory (DFT) calculations in this study were carried out with the Gaussian 16, C.01 suite of programs [68]. Geometry
- observed C3-exo-product 15. First, the active iridium catalyst will undergo oxidative addition into the aldehyde C–H bond (Figure 4). Next, the iridium hydride species will undergo exo-η2-coordination with the olefin of MeOBD to generate intermediate IN1b. Insertion of the olefin into the iridium-hydride
Graphical Abstract
Scheme 1: Previously reported metal-catalyzed reactions of heterobicyclic alkenes and applications towards th...
Scheme 2: Iridium-catalyzed hydroacylation of C1-substituted OBDs 13a–k with salicylaldehyde 14.
Scheme 3: Competition reaction of different C1-substituted OBDs.
Figure 1: Potential energy profile of the PCM solvation model for the hydrometalation/reductive elimination p...
Figure 2: Potential energy profile of the PCM solvation model for the carbometalation/reductive elimination p...
Figure 3: Potential energy profile of the PCM solvation model for the endo hydrometalation/reductive eliminat...
Figure 4: Potential energy profile of the PCM solvation model for the Ir/diene-catalyzed hydroacylation of Me...
Photoredox catalysis in nickel-catalyzed C–H functionalization
- Lusina Mantry,
- Rajaram Maayuri,
- Vikash Kumar and
- Parthasarathy Gandeepan
Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143
- for the mode of action of this cascade arylation protocol (Figure 10) [73]. In the photocatalytic cycle, the SET event between the photoexcited iridium catalyst 10-II and the substrate oxalate 33 generates a tertiary carbon-centered radical 10-IV by decarboxylation and the reduced iridium(II
- ]. Notably, this method proceeds through a unique mechanism (Figure 18) involving five steps: i) anion exchange between the iridium catalyst and nickel catalyst; ii) generation of a bromine radical and nickel(I) species in the photocatalytic cycle; iii) hydrogen atom abstraction events between the bromine
Graphical Abstract
Scheme 1: Nickel-catalyzed cross-coupling versus C‒H activation.
Figure 1: Oxidative and reductive quenching cycles of a photocatalyst. [PC] = photocatalyst, A = acceptor, D ...
Scheme 2: Photoredox nickel-catalyzed C(sp3)–H arylation of dimethylaniline (1a).
Scheme 3: Photoredox nickel-catalyzed arylation of α-amino, α-oxy and benzylic C(sp3)‒H bonds with aryl bromi...
Figure 2: Proposed catalytic cycle for the photoredox-mediated HAT and nickel catalysis enabled C(sp3)‒H aryl...
Scheme 4: Photoredox arylation of α-amino C(sp3)‒H bonds with aryl iodides.
Figure 3: Proposed mechanism for photoredox nickel-catalyzed α-amino C‒H arylation with aryl iodides.
Scheme 5: Nickel-catalyzed α-oxy C(sp3)−H arylation of cyclic and acyclic ethers.
Figure 4: Proposed catalytic cycle for the C(sp3)−H arylation of cyclic and acyclic ethers.
Scheme 6: Photochemical nickel-catalyzed C–H arylation of ethers.
Figure 5: Proposed catalytic cycle for the nickel-catalyzed arylation of ethers with aryl bromides.
Scheme 7: Nickel-catalyzed α-amino C(sp3)‒H arylation with aryl tosylates.
Scheme 8: Arylation of α-amino C(sp3)‒H bonds by in situ generated aryl tosylates from phenols.
Scheme 9: Formylation of aryl chlorides through redox-neutral 2-functionalization of 1,3-dioxolane (13).
Scheme 10: Photochemical C(sp3)–H arylation via a dual polyoxometalate HAT and nickel catalytic manifold.
Figure 6: Proposed mechanism for C(sp3)–H arylation through dual polyoxometalate HAT and nickel catalytic man...
Scheme 11: Photochemical nickel-catalyzed α-hydroxy C‒H arylation.
Scheme 12: Photochemical synthesis of fluoxetine (21).
Scheme 13: Photochemical nickel-catalyzed allylic C(sp3)‒H arylation with aryl bromides.
Figure 7: Proposed mechanism for the photochemical nickel-catalyzed allylic C(sp3)‒H arylation with aryl brom...
Scheme 14: Photochemical C(sp3)‒H arylation by the synergy of ketone HAT catalysis and nickel catalysis.
Figure 8: Proposed mechanism for photochemical C(sp3)‒H arylation by the synergy of ketone HAT catalysis and ...
Scheme 15: Benzophenone- and nickel-catalyzed photoredox benzylic C–H arylation.
Scheme 16: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)–H arylation.
Scheme 17: Photoredox and nickel-catalyzed enantioselective benzylic C–H arylation.
Figure 9: Proposed mechanism for the photoredox and nickel-catalyzed enantioselective benzylic C–H arylation.
Scheme 18: Photoredox nickel-catalyzed α-(sp3)‒H arylation of secondary benzamides with aryl bromides.
Scheme 19: Enantioselective sp3 α-arylation of benzamides.
Scheme 20: Nickel-catalyzed decarboxylative vinylation/C‒H arylation of cyclic oxalates.
Figure 10: Proposed mechanism for the nickel-catalyzed decarboxylative vinylation/C‒H arylation of cyclic oxal...
Scheme 21: C(sp3)−H arylation of bioactive molecules using mpg-CN photocatalysis and nickel catalysis.
Figure 11: Proposed mechanism for the mpg-CN/nickel photocatalytic C(sp3)–H arylation.
Scheme 22: Nickel-catalyzed synthesis of 1,1-diarylalkanes from alkyl bromides and aryl bromides.
Figure 12: Proposed mechanism for photoredox nickel-catalyzed C(sp3)–H alkylation via polarity-matched HAT.
Scheme 23: Photoredox nickel-catalyzed C(sp3)‒H alkylation via polarity-matched HAT.
Scheme 24: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)‒H alkylation of ethers.
Scheme 25: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)‒H alkylation of amides and thioethers.
Scheme 26: Photoredox and nickel-catalyzed C(sp3)‒H alkylation of benzamides with alkyl bromides.
Scheme 27: CzIPN and nickel-catalyzed C(sp3)‒H alkylation of ethers with alkyl bromides.
Figure 13: Proposed mechanism for the CzIPN and nickel-catalyzed C(sp3)‒H alkylation of ethers.
Scheme 28: Nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides and acid chlorides using trimethy...
Figure 14: Proposed catalytic cycle for the nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides ...
Scheme 29: Photochemical nickel-catalyzed C(sp3)–H methylations.
Scheme 30: Photoredox nickel catalysis-enabled alkylation of unactivated C(sp3)–H bonds with alkyl bromides.
Scheme 31: Photochemical C(sp3)–H alkenylation with alkenyl tosylates.
Scheme 32: Photoredox nickel-catalyzed hydroalkylation of internal alkynes.
Figure 15: Proposed mechanism for the photoredox nickel-catalyzed hydroalkylation of internal alkynes.
Scheme 33: Photoredox nickel-catalyzed hydroalkylation of activated alkynes with C(sp3)−H bonds.
Scheme 34: Allylation of unactivated C(sp3)−H bonds with allylic chlorides.
Scheme 35: Photochemical nickel-catalyzed α-amino C(sp3)–H allylation of secondary amides with trifluoromethyl...
Scheme 36: Photoredox δ C(sp3)‒H allylation of secondary amides with trifluoromethylated alkenes.
Scheme 37: Photoredox nickel-catalyzed acylation of α-amino C(sp3)‒H bonds of N-arylamines.
Figure 16: Proposed mechanism for the photoredox nickel-catalyzed acylation of α-amino C(sp3)–H bonds of N-ary...
Scheme 38: Photocatalytic α‑acylation of ethers with acid chlorides.
Figure 17: Proposed mechanism for the photocatalytic α‑acylation of ethers with acid chlorides.
Scheme 39: Photoredox and nickel-catalyzed C(sp3)‒H esterification with chloroformates.
Scheme 40: Photoredox nickel-catalyzed dehydrogenative coupling of benzylic and aldehydic C–H bonds.
Figure 18: Proposed reaction pathway for the photoredox nickel-catalyzed dehydrogenative coupling of benzylic ...
Scheme 41: Photoredox nickel-catalyzed enantioselective acylation of α-amino C(sp3)–H bonds with carboxylic ac...
Scheme 42: Nickel-catalyzed C(sp3)‒H acylation with N-acylsuccinimides.
Figure 19: Proposed mechanism for the nickel-catalyzed C(sp3)–H acylation with N-acylsuccinimides.
Scheme 43: Nickel-catalyzed benzylic C–H functionalization with acid chlorides 45.
Scheme 44: Photoredox nickel-catalyzed benzylic C–H acylation with N-acylsuccinimides 84.
Scheme 45: Photoredox nickel-catalyzed acylation of indoles 86 with α-oxoacids 87.
Scheme 46: Nickel-catalyzed aldehyde C–H functionalization.
Figure 20: Proposed catalytic cycle for the photoredox nickel-catalyzed aldehyde C–H functionalization.
Scheme 47: Photoredox carboxylation of methylbenzenes with CO2.
Figure 21: Proposed mechanism for the photoredox carboxylation of methylbenzenes with CO2.
Scheme 48: Decatungstate photo-HAT and nickel catalysis enabled alkene difunctionalization.
Figure 22: Proposed catalytic cycle for the decatungstate photo-HAT and nickel catalysis enabled alkene difunc...
Scheme 49: Diaryl ketone HAT catalysis and nickel catalysis enabled dicarbofunctionalization of alkenes.
Figure 23: Proposed catalytic mechanism for the diaryl ketone HAT catalysis and nickel catalysis enabled dicar...
Scheme 50: Overview of photoredox nickel-catalyzed C–H functionalizations.
A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries
- Guido Gambacorta,
- James S. Sharley and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates
- Olusesan K. Koleoso,
- Matthew Turner,
- Felix Plasser and
- Marc C. Kimber
Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165
- -acyliminium intermediate is provided to explain the addition product distribution. Results and Discussion We began our study by using the iridium catalyst Ir[(ppy)2(dtbbpy)]PF6 (17) and the reaction conditions used in the addition of amine nucleophiles to enamides [48][50]. By exploiting these reaction
Graphical Abstract
Scheme 1: Electrophilic activation of allenamides.
Scheme 2: The planned intramolecular radical addition to allenamides generating the conjugated N-acyliminium ...
Scheme 3: Photoredox Ir-catalyzed intermolecular addition of bromide 18 and aniline 16 to allenamide 15.
Scheme 4: Reaction scope (a) allenamide; (b) arylamine nucleophile; (c) alcohol nucleophile.
Scheme 5: (a) Tentative mechanism for the photoredox-catalyzed formation of the conjugated N-acyliminium inte...
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
- ). Eosin Y was inefficient under these conditions (Table 1, entry 20). Since [Ru(bpy)3]Cl2 is significantly cheaper than the iridium catalyst, the former was used in further reactions. Regarding the addition of different bases, the yield remained unchanged, when lutidine was added. Potassium carbonate 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.
Six-fold C–H borylation of hexa-peri-hexabenzocoronene
- Mai Nagase,
- Kenta Kato,
- Akiko Yagi,
- Yasutomo Segawa and
- Kenichiro Itami
Beilstein J. Org. Chem. 2020, 16, 391–397, doi:10.3762/bjoc.16.37
- calculations. The spectra revealed a bathochromic shift of absorption bands compared with unsubstituted HBC under the effect of the σ-donation of boryl groups. Keywords: C–H borylation; hexa-peri-hexabenzocoronene; iridium catalyst; X-ray crystallography; Introduction Polycyclic aromatic hydrocarbons (PAHs
- borylation of unsubstituted HBC. HBC was pulverized by a ball mill prior to use. First, we attempted the iridium catalyst and reagents that we have reported as the suitable C–H borylation conditions for warped nanographene: [Ir(OMe)cod]2, 3,4,7,8-tetramethyl-1,10-phenanthroline (tmphen), HBpin (Bpin: 4,4,5,5
Graphical Abstract
Figure 1: C–H functionalization of HBCs. (a) Perchlorinated HBC. (b) Borylated HBC substituted by 2,4,6-trime...
Figure 2: Synthesis of hexaborylated HBC 1. (a) Solvent screening of six-fold C–H borylation of unsubstituted...
Figure 3: The structure of 1 confirmed by X-ray crystallographic analysis. (a) ORTEP drawing of 1 with therma...
Figure 4: Photophysical properties of 1. (a) UV–vis absorption (solid lines) spectra, fluorescence (dotted li...
Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis
- Amrita Das,
- Mitasree Maity,
- Simon Malcherek,
- Burkhard König and
- Julia Rehbein
Beilstein J. Org. Chem. 2018, 14, 2520–2528, doi:10.3762/bjoc.14.228
- -trimethoxybenzene in CH3CN. (b) Changes in the fluorescence spectra upon the addition of diphenyl disulfide in CH3CN. (c) Stern–Volmer quenching plot of iridium catalyst in the presence of 1,2,4-trimethoxybenzene and diphenyl disulfide. Kq (arene) = 318 ± 2.6 M−1 L and Kq (disulfide) = 36 ± 0.7 M−1 L. Black line
Graphical Abstract
Figure 1: Selected examples of sulfenylated heterocycles used in pharmaceuticals and material chemistry.
Scheme 1: Synthetic routes to organosulfur compounds.
Scheme 2: Aryl sulfide synthesis.
Scheme 3: Substrate scope for arylthiol syntheses. The reaction was performed with 1a–g (0.1 mmol) and 2a–d (...
Figure 2: Crystal structures of compounds 3a, 3d, 3e and 3i.
Scheme 4: Radical trapping experiments.
Figure 3: (a) Changes in the fluorescence spectra (in this case intensity, λEx = 455 nm) of [Ir(dF(CF3)ppy)2(...
Scheme 5: Proposed mechanism for visible light mediated direct C–H sulfenylation.
Figure 4: Black line: UV–vis spectrum of the degassed [Ir] + 1,3,5-TMB mixture (solution A) in ACN. Blue and ...
CF3SO2X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF3SO2Cl
- Hélène Chachignon,
- Hélène Guyon and
- Dominique Cahard
Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273
- interestingly, when the reaction was performed using an aryl or alkylsulfonyl chloride, instead of trifluoromethanesulfonyl chloride, no extrusion of the SO2 moiety was observed, and the sulfonated products were recovered. The reaction mechanism involved excitation of the iridium catalyst under visible light to
Graphical Abstract
Scheme 1: Trifluoromethylation of silyl enol ethers.
Scheme 2: Continuous flow trifluoromethylation of ketones under photoredox catalysis.
Scheme 3: Trifluoromethylation of enol acetates.
Scheme 4: Photoredox-catalysed tandem trifluoromethylation/cyclisation of N-arylacrylamides: a route to trifl...
Scheme 5: Tandem trifluoromethylation/cyclisation of N-arylacrylamides using BiOBr nanosheets catalysis.
Scheme 6: Photoredox-catalysed trifluoromethylation/desulfonylation/cyclisation of N-tosyl acrylamides (bpy: ...
Scheme 7: Photoredox-catalysed trifluoromethylation/aryl migration/desulfonylation of N-aryl-N-tosylacrylamid...
Scheme 8: Proposed mechanism for the trifluoromethylation/aryl migration/desulfonylation (/cyclisation) of N-...
Scheme 9: Photoredox-catalysed trifluoromethylation/cyclisation of N-methacryloyl-N-methylbenzamide derivativ...
Scheme 10: Photoredox-catalysed trifluoromethylation/cyclisation of N-methylacryloyl-N-methylbenzamide derivat...
Scheme 11: Photoredox-catalysed trifluoromethylation/dearomatising spirocyclisation of a N-benzylacrylamide de...
Scheme 12: Photoredox-catalysed trifluoromethylation/cyclisation of an unactivated alkene.
Scheme 13: Asymmetric radical aminotrifluoromethylation of N-alkenylurea derivatives using a dual CuBr/chiral ...
Scheme 14: Aminotrifluoromethylation of an N-alkenylurea derivative using a dual CuBr/phosphoric acid catalyti...
Scheme 15: 1,2-Formyl- and 1,2-cyanotrifluoromethylation of alkenes under photoredox catalysis.
Scheme 16: First simultaneous introduction of the CF3 moiety and a Cl atom onto alkenes.
Scheme 17: Chlorotrifluoromethylaltion of terminal, 1,1- and 1,2-substituted alkenes.
Scheme 18: Chorotrifluoromethylation of electron-deficient alkenes (DCE = dichloroethane).
Scheme 19: Cascade trifluoromethylation/cyclisation/chlorination of N-allyl-N-(benzyloxy)methacrylamide.
Scheme 20: Cascade trifluoromethylation/cyclisation (/chlorination) of diethyl 2-allyl-2-(3-methylbut-2-en-1-y...
Scheme 21: Trifluoromethylchlorosulfonylation of allylbenzene derivatives and aliphatic alkenes.
Scheme 22: Access to β-hydroxysulfones from CF3-containing sulfonyl chlorides through a photocatalytic sequenc...
Scheme 23: Cascade trifluoromethylchlorosulfonylation/cyclisation reaction of alkenols: a route to trifluorome...
Scheme 24: First direct C–H trifluoromethylation of arenes and proposed mechanism.
Scheme 25: Direct C–H trifluoromethylation of five- and six-membered (hetero)arenes under photoredox catalysis....
Scheme 26: Alternative pathway for the C–H trifluoromethylation of (hetero)arenes under photoredox catalysis.
Scheme 27: Direct C–H trifluoromethylation of five- and six-membered ring (hetero)arenes using heterogeneous c...
Scheme 28: Trifluoromethylation of terminal olefins.
Scheme 29: Trifluoromethylation of enamides.
Scheme 30: (E)-Selective trifluoromethylation of β-nitroalkenes under photoredox catalysis.
Scheme 31: Photoredox-catalysed trifluoromethylation/cyclisation of an o-azidoarylalkynes.
Scheme 32: Regio- and stereoselective chlorotrifluoromethylation of alkynes.
Scheme 33: PMe3-mediated trifluoromethylsulfenylation by in situ generation of CF3SCl.
Scheme 34: (EtO)2P(O)H-mediated trifluoromethylsulfenylation of (hetero)arenes and thiols.
Scheme 35: PPh3/NaI-mediated trifluoromethylsulfenylation of indole derivatives.
Scheme 36: PPh3/n-Bu4NI mediated trifluoromethylsulfenylation of thiophenol derivatives.
Scheme 37: PPh3/Et3N mediated trifluoromethylsulfinylation of benzylamine.
Scheme 38: PCy3-mediated trifluoromethylsulfinylation of azaarenes, amines and phenols.
Scheme 39: Mono- and dichlorination of carbon acids.
Scheme 40: Monochlorination of (N-aryl-N-hydroxy)acylacetamides.
Scheme 41: Examples of the synthesis of heterocycles fused with β-lactams through a chlorination/cyclisation p...
Scheme 42: Enantioselective chlorination of β-ketoesters and oxindoles.
Scheme 43: Enantioselective chlorination of 3-acyloxazolidin-2-one derivatives (NMM = N-methylmorpholine).
Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds
- Santanu Hati,
- Ulrike Holzgrabe and
- Subhabrata Sen
Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162
- ]. Recently Xiao et al. [94] has reported an acceptor-free oxidative dehydrogenation with a versatile iridium catalyst (Scheme 35). A variety of tetrahydroquinolines 93 were converted to the aromatic quinoline 94 using the iridium catalyst in 2,2,2-trifluoroethanol (TFE) at higher temperature. As an extension
Graphical Abstract
Figure 1: Representative bioactive heterocycles.
Scheme 1: The concept of oxidative dehydrogenation.
Scheme 2: IBX-mediated oxidative dehydrogenation of various heterocycles [31-34].
Scheme 3: Potential mechanism of IBX-mediated oxidative dehydrogenation of N-heterocycles [31-34].
Scheme 4: IBX-mediated room temperature one-pot condensation–oxidative dehydrogenation of o-aminobenzylamines....
Scheme 5: Anhydrous cerium chloride-catalyzed, IBX-mediated oxidative dehydrogenation of various heterocycles...
Scheme 6: Oxidative dehydrogenation of quinazolinones with I2 and DDQ [37-40].
Scheme 7: DDQ-mediated oxidative dehydrogenation of thiazolidines and oxazolidines.
Scheme 8: Oxone-mediated oxidative dehydrogenation of intermediates from o-phenylenediamine and o-aminobenzyl...
Scheme 9: Transition metal-free oxidative cross-dehydrogenative coupling.
Scheme 10: NaOCl-mediated oxidative dehydrogenation.
Scheme 11: NBS-mediated oxidative dehydrogenation of tetrahydro-β-carbolines.
Scheme 12: One-pot synthesis of various methyl(hetero)arenes from o-aminobenzamide in presence of di-tert-buty...
Scheme 13: Oxidative dehydrogenation of 1, 4-DHPs.
Scheme 14: Synthesis of quinazolines in the presence of MnO2.
Scheme 15: Selenium dioxide and potassium dichromate-mediated oxidative dehydrogenation of tetrahydro-β-carbol...
Scheme 16: Synthesis of substituted benzazoles in the presence of barium permanganate.
Scheme 17: Oxidative dehydrogenation with phenanthroline-based catalysts. PPTS = pyridinium p-toluenesulfonic ...
Scheme 18: Oxidative dehydrogenation with Flavin mimics.
Scheme 19: o-Quinone based bioinspired catalysts for the synthesis of dihydroisoquinolines.
Scheme 20: Cobalt-catalyzed aerobic dehydrogenation of Hantzch 1,4-DHPs and pyrazolines.
Scheme 21: Mechanism of cobalt-catalyzed aerobic dehydrogenation of Hantzch 1,4-DHPs.
Scheme 22: DABCO and TEMPO-catalyzed aerobic oxidative dehydrogenation of quinazolines and 4H-3,1-benzoxazines....
Scheme 23: Putative mechanism for Cu(I)–DABCO–TEMPO catalyzed aerobic oxidative dehydrogenation of tetrahydroq...
Scheme 24: Potassium triphosphate modified Pd/C catalysts for the oxidative dehydrogenation of tetrahydroisoqu...
Scheme 25: Ruthenium-catalyzed polycyclic heteroarenes.
Scheme 26: Plausible mechanism of the ruthenium-catalyzed dehydrogenation.
Scheme 27: Bi-metallic platinum/iridium alloyed nanoclusters and 5,5’,6,6’-tetrahydroxy-3,3,3’,3’-tetramethyl-...
Scheme 28: Magnesium iodide-catalyzed synthesis of quinazolines.
Scheme 29: Ferrous chloride-catalyzed aerobic dehydrogenation of 1,2,3,4-tetrahydroquinolines.
Scheme 30: Cu(I)-catalyzed oxidative aromatization of indoles.
Scheme 31: Putative mechanism of the transformation.
Scheme 32: Oxidative dehydrogenation of pyrimidinones and pyrimidines.
Scheme 33: Putative mechanisms (radical and metal-catalyzed) of the transformation.
Scheme 34: Ferric chloride-catalyzed, TBHP-oxidized synthesis of substituted quinazolinones and arylquinazolin...
Scheme 35: Iridium-catalyzed oxidative dehydrogenation of quinolines.
Scheme 36: Microwave-assisted synthesis of β-carboline with a catalytic amount of Pd/C in lithium carbonate at...
Scheme 37: 4-Methoxy-TEMPO-catalyzed aerobic oxidative synthesis of 2-substituted benzazoles.
Scheme 38: Plausible mechanism of the 4-methoxy-TEMPO-catalyzed transformation.
Scheme 39: One-pot synthesis of 2-arylquinazolines, catalyzed by 4-hydroxy-TEMPO.
Scheme 40: Oxidative dehydrogenation – a key step in the synthesis of AZD8926.
Scheme 41: Catalytic oxidative dehydrogenation of tetrahydroquinolines to afford bioactive molecules.
Scheme 42: Iodobenzene diacetate-mediated synthesis of β-carboline natural products.
Synthesis of 1-indanones with a broad range of biological activity
- Marika Turek,
- Dorota Szczęsna,
- Marek Koprowski and
- Piotr Bałczewski
Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48
- carried out in the presence of an iridium catalyst and antimony hexafluoride (AgSbF6) under mild conditions. The starting chalcones were almost completely converted into 1-indanones 138–142 and isolated in very good yields. Our research group synthesized 3-aryl-1-indanones 148 and previously unknown 3
Graphical Abstract
Figure 1: Biologically active 1-indanones and their structural analogues.
Figure 2: Number of papers about (a) 1-indanones, (b) synthesis of 1-indanones.
Scheme 1: Synthesis of 1-indanone (2) from hydrocinnamic acid (1).
Scheme 2: Synthesis of 1-indanone (2) from 3-(2-bromophenyl)propionic acid (3).
Scheme 3: Synthesis of 1-indanones 5 from 3-arylpropionic acids 4.
Scheme 4: Synthesis of kinamycin (9a) and methylkinamycin C (9b).
Scheme 5: Synthesis of trifluoromethyl-substituted arylpropionic acids 12, 1-indanones 13 and dihydrocoumarin...
Scheme 6: Synthesis of 1-indanones 16 from benzoic acids 15.
Scheme 7: Synthesis of 1-indanones 18 from arylpropionic and 3-arylacrylic acids 17.
Scheme 8: The NbCl5-induced one-step synthesis of 1-indanones 22.
Scheme 9: Synthesis of biologically active 1-indanone derivatives 26.
Scheme 10: Synthesis of enantiomerically pure indatraline ((−)-29).
Scheme 11: Synthesis of 1-indanone (2) from the acyl chloride 30.
Scheme 12: Synthesis of the mechanism-based inhibitors 33 of coelenterazine.
Scheme 13: Synthesis of the indane 2-imidazole derivative 37.
Scheme 14: Synthesis of fluorinated PAHs 41.
Scheme 15: Synthesis of 1-indanones 43 via transition metal complexes-catalyzed carbonylative cyclization of m...
Scheme 16: Synthesis of 6-methyl-1-indanone (46).
Scheme 17: Synthesis of 1-indanone (2) from ester 48.
Scheme 18: Synthesis of benzopyronaphthoquinone 51 from the spiro-1-indanone 50.
Scheme 19: Synthesis of the selective endothelin A receptor antagonist 55.
Scheme 20: Synthesis of 1-indanones 60 from methyl vinyl ketone (57).
Scheme 21: Synthesis of 1-indanones 64 from diethyl phthalate 61.
Scheme 22: Synthesis of 1-indanone derivatives 66 from various Meldrum’s acids 65.
Scheme 23: Synthesis of halo 1-indanones 69.
Scheme 24: Synthesis of substituted 1-indanones 71.
Scheme 25: Synthesis of spiro- and fused 1-indanones 73 and 74.
Scheme 26: Synthesis of spiro-1,3-indanodiones 77.
Scheme 27: Mechanistic pathway for the NHC-catalyzed Stetter–Aldol–Michael reaction.
Scheme 28: Synthesis of 2-benzylidene-1-indanone derivatives 88a–d.
Scheme 29: Synthesis of 1-indanone derivatives 90a–i.
Scheme 30: Synthesis of 1-indanones 96 from o-bromobenzaldehydes 93 and alkynes 94.
Scheme 31: Synthesis of 3-hydroxy-1-indanones 99.
Scheme 32: Photochemical preparation of 1-indanones 103 from ketones 100.
Scheme 33: Synthesis of chiral 3-aryl-1-indanones 107.
Scheme 34: Photochemical isomerization of 2-methylbenzil 108.
Scheme 35: Synthesis of 2-hydroxy-1-indanones 111a–c.
Scheme 36: Synthesis of 1-indanone derivatives 113 and 114 from η6-1,2-dioxobenzocyclobutene complex 112.
Scheme 37: Synthesis of nakiterpiosin (117).
Scheme 38: Synthesis of 2-alkyl-1-indanones 120.
Scheme 39: Synthesis of fluorine-containing 1-indanone derivatives 123.
Scheme 40: Synthesis of 2-benzylidene and 2-benzyl-1-indanones 126, 127 from the chalcone 124.
Scheme 41: Synthesis of 2-bromo-6-methoxy-3-phenyl-1-indanone (130).
Scheme 42: Synthesis of combretastatin A-4-like indanones 132a–s.
Figure 3: Chemical structures of investigated dienones 133 and synthesized cyclic products 134–137.
Figure 4: Chemical structures of 1-indanones and their heteroatom analogues 138–142.
Scheme 43: Synthesis of 2-phosphorylated and 2-non-phosphorylated 1-indanones 147 and 148 from β-ketophosphona...
Scheme 44: Photochemical synthesis of 1-indanone derivatives 150, 153a, 153b.
Scheme 45: Synthesis of polysubstituted-1-indanones 155, 157.
Scheme 46: Synthesis of 1-indanones 159a–g from α-arylpropargyl alcohols 158 using RhCl(PPh3)3 as a catalyst.
Scheme 47: Synthesis of optically active 1-indanones 162 via the asymmetric Rh-catalyzed isomerization of race...
Scheme 48: Mechanism of the Rh-catalyzed isomerization of α-arylpropargyl alcohols 161 to 1-indanones 162.
Figure 5: Chemical structure of abicoviromycin (168) and its new benzo derivative 169.
Scheme 49: Synthesis of racemic benzoabicoviromycin 172.
Scheme 50: Synthesis of [14C]indene 176.
Scheme 51: Synthesis of indanone derivatives 178–180.
Scheme 52: Synthesis of racemic pterosin A 186.
Scheme 53: Synthesis of trans-2,3-disubstituted 1-indanones 189.
Scheme 54: Synthesis of 3-aryl-1-indanone derivatives 192.
Scheme 55: Synthesis of 1-indanone derivatives 194 from 3-(2-iodoaryl)propanonitriles 193.
Scheme 56: Synthesis of 1-indanones 200–204 by cyclization of aromatic nitriles.
Scheme 57: Synthesis of 1,1’-spirobi[indan-3,3’-dione] derivative 208.
Scheme 58: Total synthesis of atipamezole analogues 211.
Scheme 59: Synthesis of 3-[4-(1-piperidinoethoxy)phenyl]spiro[indene-1,1’-indan]-5,5’-diol hydrochloride 216.
Scheme 60: Synthesis of 3-arylindan-1-ones 219.
Scheme 61: Synthesis of 2-hydroxy-1-indanones 222.
Scheme 62: Synthesis of the 1-indanone 224 from the THP/MOM protected chalcone epoxide 223.
Scheme 63: Synthesis of 1-indanones 227 from γ,δ-epoxy ketones 226.
Scheme 64: Synthesis of 2-hydroxy-2-methylindanone (230).
Scheme 65: Synthesis of 1-indanone derivatives 234 from cyclopropanol derivatives 233.
Scheme 66: Synthesis of substituted 1-indanone derivatives 237.
Scheme 67: Synthesis of 7-methyl substituted 1-indanone 241 from 1,3-pentadiene (238) and 2-cyclopentenone (239...
Scheme 68: Synthesis of disubstituted 1-indanone 246 from the siloxydiene 244 and 2-cyclopentenone 239.
Scheme 69: Synthesis of 5-hydroxy-1-indanone (250) via the Diels–Alder reaction of 1,3-diene 248 with sulfoxid...
Scheme 70: Synthesis of halogenated 1-indanones 253a and 253b.
Scheme 71: Synthesis of 1-indanones 257 and 258 from 2-bromocyclopentenones 254.
Scheme 72: Synthesis of 1-indanone 261 from 2-bromo-4-acetoxy-2-cyclopenten-1-one (260) and 1,2-dihydro-4-viny...
Scheme 73: Synthesis of 1-indanone 265 from 1,2-dihydro-7-methoxy-4-vinylnaphthalene (262) and bromo-substitut...
Scheme 74: Synthesis of 1-indanone 268 from dihydro-3-vinylphenanthrene 266 and 4-acetoxy-2-cyclopenten-1-one (...
Scheme 75: Synthesis of 1-indanone 271 from phenylselenyl-substituted cyclopentenone 268.
Scheme 76: Synthesis of 1-indanone 272 from the trienone 270.
Scheme 77: Synthesis of the 1-indanone 276 from the aldehyde 273.
Scheme 78: Synthesis of 1-indanones 278 and 279.
Scheme 79: Synthesis of 1-indanone 285 from octa-1,7-diyne (282) and cyclopentenone 239.
Scheme 80: Synthesis of benz[f]indan-1-one (287) from cyclopentenone 239 and o-bis(dibromomethyl)benzene (286)....
Scheme 81: Synthesis of 3-methyl-substituted benz[f]indan-1-one 291 from o-bis(dibromomethyl)benzene (286) and...
Scheme 82: Synthesis of benz[f]indan-1-one (295) from the anthracene epidioxide 292.
Scheme 83: Synthesis of 1-indanone 299 from homophthalic anhydride 298 and cyclopentynone 297.
Scheme 84: Synthesis of cyano-substituted 1-indanone derivative 301 from 2-cyanomethylbenzaldehyde (300) and c...
Scheme 85: Synthesis of 1-indanone derivatives 303–305 from ketene dithioacetals 302.
Scheme 86: Synthesis of 1-indanones 309–316.
Scheme 87: Mechanism of the hexadehydro-Diels–Alder (HDDA) reaction.
Scheme 88: Synthesis of 1-indenone 318 and 1-indanones 320 and 321 from tetraynes 317 and 319.
Scheme 89: Synthesis of 1-indanone 320 from the triyn 319.
Scheme 90: Synthesis 1-indanone 328 from 2-methylfuran 324.
Scheme 91: Synthesis of 1-indanones 330 and 331 from furans 329.
Scheme 92: Synthesis of 1-indanone 333 from the cycloadduct 332.
Scheme 93: Synthesis of (S)-3-arylindan-1-ones 335.
Scheme 94: Synthesis of (R)-2-acetoxy-1-indanone 338.
Figure 6: Chemical structures of obtained cyclopenta[α]phenanthrenes 339.
Scheme 95: Synthesis of the benzoindanone 343 from arylacetaldehyde 340 with 1-trimethylsilyloxycyclopentene (...
Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update
- Bin Yu,
- Hui Xing,
- De-Quan Yu and
- Hong-Min Liu
Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98
- alkoxide species C. Reductive elimination of species C gave the product and regenerated the active iridium catalyst. Recently, Qiu and co-workers developed a novel chiral ligand L5 based on a chiral-bridged biphenyl backbone and successfully achieved the asymmetric addition of arylboronic acids to N
Graphical Abstract
Figure 1: 3-Hydroxyoxindole-containing natural products and biologically active molecules.
Scheme 1: Chiral CNN pincer Pd(II) complex 1 catalyzed asymmetric allylation of isatins.
Scheme 2: Asymmetric allylation of ketimine catalyzed by the chiral CNN pincer Pd(II) complex 2.
Scheme 3: Pd/L1 complex-catalyzed asymmetric allylation of 3-O-Boc-oxindoles.
Scheme 4: Cu(OTf)2-catalyzed asymmetric direct addition of acetonitrile to isatins.
Scheme 5: Chiral tridentate Schiff base/Cu complex catalyzed asymmetric Friedel–Crafts alkylation of isatins ...
Scheme 6: Guanidine/CuI-catalyzed asymmetric alkynylation of isatins with terminal alkynes.
Scheme 7: Asymmetric intramolecular direct hydroarylation of α-ketoamides.
Scheme 8: Plausible catalytic cycle for the direct hydroarylation of α-ketoamides.
Scheme 9: Ir-catalyzed asymmetric arylation of isatins with arylboronic acids.
Scheme 10: Enantioselective decarboxylative addition of β-ketoacids to isatins.
Scheme 11: Ruthenium-catalyzed hydrohydroxyalkylation of olefins and 3-hydroxy-2-oxindoles.
Scheme 12: Proposed catalytic mechanism and stereochemical model.
Scheme 13: In-catalyzed allylation of isatins with stannylated reagents.
Scheme 14: Modified protocol for the synthesis of allylated 3-hydroxyoxindoles.
Scheme 15: Hg-catalyzed asymmetric allylation of isatins with allyltrimethylsilanes.
Scheme 16: Enantioselective additions of organoborons to isatins.
Scheme 17: Asymmetric aldol reaction of isatins with cyclohexanone.
Scheme 18: Enantioselective aldol reactions of aliphatic aldehydes with isatin derivatives and the plausible t...
Scheme 19: Enantioselective aldol reaction of isatins and 2,2-dimethyl-1,3-dioxan-5-one.
Scheme 20: Asymmetric aldol reactions between ketones and isatins.
Scheme 21: Phenylalanine lithium salt-catalyzed asymmetric synthesis of 3-alkyl-3-hydroxyoxindoles.
Scheme 22: Aldolization between isatins and dihydroxyacetone derivatives.
Scheme 23: One-pot asymmetric synthesis of convolutamydine A.
Scheme 24: Asymmetric aldol reactions of cyclohexanone and acetone with isatins.
Scheme 25: Aldol reactions of acetone with isatins.
Scheme 26: Aldol reactions of ketones with isatins.
Scheme 27: Enantioselective allylation of isatins.
Scheme 28: Asymmetric aldol reaction of trifluoromethyl α-fluorinated β-keto gem-diols with isatins.
Scheme 29: Plausible mechanism proposed for the asymmetric aldol reaction.
Scheme 30: Asymmetric aldol reaction of 1,1-dimethoxyacetone with isatins.
Scheme 31: Enantioselective Friedel-Crafts reaction of phenols with isatins.
Scheme 32: Enantioselective addition of 1-naphthols with isatins.
Scheme 33: Enantioselective aldol reaction between 3-acetyl-2H-chromen-2-ones and isatins.
Scheme 34: Stereoselective Mukaiyama–aldol reaction of fluorinated silyl enol ethers with isatins.
Scheme 35: Asymmetric vinylogous Mukaiyama–aldol reaction between 2-(trimethylsilyloxy)furan and isatins.
Scheme 36: β-ICD-catalyzed MBH reactions of isatins with maleimides.
Scheme 37: β-ICD-catalyzed MBH reactions of 7-azaisatins with maleimides and activated alkenes.
Scheme 38: Enantioselective aldol reaction of isatins with ketones.
Scheme 39: Direct asymmetric vinylogous aldol reactions of allyl ketones with isatins.
Scheme 40: Enantioselective aldol reactions of ketones with isatins.
Scheme 41: The MBH reaction of isatins with α,β-unsaturated γ-butyrolactam.
Scheme 42: Reactions of tert-butyl hydrazones with isatins followed by oxidation.
Scheme 43: Aldol reactions of isatin derivatives with ketones.
Scheme 44: Enantioselective decarboxylative cyanomethylation of isatins.
Scheme 45: Catalytic kinetic resolution of 3-hydroxy-3-substituted oxindoles.
Scheme 46: Lewis acid catalyzed Friedel–Crafts alkylation of 3-hydroxy-2-oxindoles with electron-rich phenols.
Scheme 47: Lewis acid catalyzed arylation of 3-hydroxyoxindoles with aromatics.
Scheme 48: Synthetic application of 3-arylated disubstituted oxindoles in the construction of core structures ...
Scheme 49: CPA-catalyzed dearomatization and arylation of 3-indolyl-3-hydroxyoxindoles with tryptamines and 3-...
Scheme 50: CPA-catalyzed enantioselective decarboxylative alkylation of β-keto acids with 3-hydroxy-3-indolylo...
Scheme 51: BINOL-derived imidodiphosphoric acid-catalyzed enantioselective Friedel–Crafts reactions of indoles...
Scheme 52: CPA-catalyzed enantioselective allylation of 3-indolylmethanols.
Scheme 53: 3-Indolylmethanol-based substitution and cycloaddition reactions.
Scheme 54: CPA-catalyzed asymmetric [3 + 3] cycloaddtion reactions of 3-indolylmethanols with azomethine ylide...
Scheme 55: CPA-catalyzed three-component cascade Michael/Pictet–Spengler reactions of 3-indolylmethanols and a...
Scheme 56: Acid-promoted chemodivergent and stereoselective synthesis of diverse indole derivatives.
Scheme 57: CPA-catalyzed asymmetric formal [3 + 2] cycloadditions.
Scheme 58: CPA-catalyzed enantioselective cascade reactions for the synthesis of C7-functionlized indoles.
Scheme 59: Lewis acid-promoted Prins cyclization of 3-allyl-3-hydroxyoxindoles with aldehydes.
Scheme 60: Ga(OTf)3-catalyzed reactions of allenols and phenols.
Scheme 61: I2-catalyzed construction of pyrrolo[2.3.4-kl]acridines from enaminones and 3-indolyl-3-hydroxyoxin...
Scheme 62: CPA-catalyzed asymmetric aza-ene reaction of 3-indolylmethanols with cyclic enaminones.
Scheme 63: Asymmetric α-alkylation of aldehydes with 3-indolyl-3-hydroxyoxindoles.
Scheme 64: Organocatalytic asymmetric α-alkylation of enolizable aldehydes with 3-indolyl-3-hydroxyoxindoles a...
Enantioselective carbenoid insertion into C(sp3)–H bonds
- J. V. Santiago and
- A. H. L. Machado
Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87
- literature of an enantioselective insertion of an iridium carbenoid into C(sp3)–H bonds. Che and coworkers introduced the first porphyrin-based chiral iridium catalyst (−)-65 to insertion of carbenoids into C(sp3)–H bonds [52]. The reaction with 1,4-cyclohexadiene was promoted by 1 mol % of the catalyst at
- , ranging from 2.5:1 to >20:1, favoring the anti-product, in a complementary sense when compared to the results reported by Suematsu and Katsuki for iridium catalyst 61a (Table 8). Poor to excellent yields and high enantioselectivity were reported for the main product. The chiral porphyrin-based iridium
- group Ar1 (p-CH3Ph = 24 h; p-FPh, m-ClPh, m-BrPh = 10 min) and the enantioselectivity drops from 70–80% ee to less than 50% ee when Ar1 is m-ClPh or m-BrPh. In 2013, Davies, Blakey and coworkers reported a new iridium catalyst to perform a carbenoid insertion into the C(sp3)–H bond (Scheme 15) [54]. The
Graphical Abstract
Figure 1: Singlet carbene, triplet carbene and carbenoids.
Figure 2: Classification of the carbenoid intermediates by the electronic nature of the groups attached to th...
Figure 3: Chiral bis(oxazoline) ligands used in enantioselective copper carbenoid insertion.
Scheme 1: Pioneering work of Peter Yates on the carbenoid insertion reaction into X–H bonds (where X = O, S, ...
Scheme 2: Copper carbenoid insertion into C(sp3)–H bond of a stereogenic center with full retention of the as...
Scheme 3: Carbenoid insertion into a C(sp3)–H bond as the key step of the Taber’s (+)-α-cuparenone (8) synthe...
Scheme 4: First enantioselective carbenoid insertion into C–O bonds catalyzed by chiral metallic complexes.
Figure 4: Chemical structures of complexes (R)-18 and (S)-18.
Scheme 5: Asymmetric carbenoid insertions into C(sp3)–H bonds of cycloalkanes catalyzed by chiral rhodium car...
Scheme 6: First diastereo and enantioselective intermolecular carbenoid insertion into tetrahydrofuran C(sp3)...
Scheme 7: Simplified mechanism of the carbenoid insertion into a C(sp3)–H bond.
Scheme 8: Nakamura’s carbenoid insertion into a C(sp3)–H bond catalytic cycle.
Scheme 9: Investigation of the relationship between the electronic characteristics of the substituent X attac...
Scheme 10: Empirical model to predict the stereoselectivity of the donor/acceptor dirhodium carbenoid insertio...
Scheme 11: Asymmetric insertion of copper carbenoids in C(sp3)–H bonds to prepare trans-γ-lactam.
Figure 5: Iridium catalysts used by Suematsu and Katsuki for carbenoid insertion into C(sp3)–H bonds.
Scheme 12: Chiral porphyrin iridium complex catalyzes the carbenoid insertion into bis-allylic C(sp3)–H bonds.
Scheme 13: Chiral porphyrin iridium complex catalyzes the carbenoid insertion into tetrahydrofuran C(sp3)–H bo...
Scheme 14: Chiral porphyrin–iridium complex catalyzes the intramolecular carbenoid insertion into C(sp3)–H bon...
Scheme 15: Chiral bis(oxazoline)–iridium complex catalyzes the carbenoid insertion into bis-allylic C(sp3)–H b...
Scheme 16: New cyclopropylcarboxylate-based chiral catalyst to enantioselective carbenoid insertion into the e...
Scheme 17: Regio- and enantioselective carbenoid insertion into the C(sp3)–H bond catalyzed by a new bulky cyc...
Scheme 18: Regio and diastereoselective carbenoid insertion into the C(sp3)–H bond catalyzed by a new bulky cy...
Scheme 19: 2,2,2-Trichloroethyl (TCE) aryldiazoacetates to improve the scope, regio- and enantioselective of t...
Scheme 20: Sequential C–H functionalization approach to 2,3-dihydrobenzofurans.
Scheme 21: Enantioselective intramolecular rhodium carbenoid insertion into C(sp3)–H bonds to afford cis-disub...
Scheme 22: Enantioselective intramolecular rhodium carbenoid insertion into C(sp3)–H bonds to afford cis-2-vin...
Scheme 23: First rhodium porphyrin-based catalyst for enantioselective carbenoid insertion into C(sp3)–H bond.
Scheme 24: Rhodium porphyrin-based catalyst for enantioselective carbenoid insertion into benzylic C(sp3)–H bo...
Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane
- Mamoru Tobisu,
- Takuya Igarashi and
- Naoto Chatani
Beilstein J. Org. Chem. 2016, 12, 654–661, doi:10.3762/bjoc.12.65
- ) system. Results and Discussion On the basis of a superior reactivity of indoles in several C–H borylation reactions [7][8][9], we initially examined the borylation of indole 2 with aminoborane 1g using an iridium catalyst under forcing conditions (140 °C, 15 h). Although all the attempts to isolate an
- 3, entry 5). Naphthalene also underwent borylation with 1g at the less hindered 2-position (Table 3, entry 6). Our protocol was performed on a gram scale without any difficulty using a lower loading of the iridium catalyst (Scheme 2, top). Using 1g as the boron source in C–H borylation reactions has
Graphical Abstract
Scheme 1: Catalytic C–H borylation of arenes and related reported boron sources.
Scheme 2: Scalability and derivatization.
Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds
- Dominik Lenhart and
- Thorsten Bach
Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86
- -aminomethyl radicals [43][44][45] to enones. N-Methyl-N-((trimethylsilyl)methyl)aniline (5) for example served as substrate for the alkylation of 2-cyclohexenone (6) employing iridium catalyst 7. When using the amine as the limiting reagent and an excess of enone (1.5 equiv) product 8 was obtained in 70
- reactions to other cyclic α,β-unsaturated carbonyl compounds. In particular, we were interested to see whether cyclization reactions as for product 4 would be observed when using α,β-unsaturated lactones and lactams in combination with a silylated amine and an iridium catalyst. In this article, we provide
Graphical Abstract
Scheme 1: PET-catalyzed addition of N,N-dimethylaniline (1) to furan-2(5H)-one 2 [38] and of N-methyl-N-((trimeth...
Scheme 2: Ir-catalyzed formation of tricyclic product 10 by a domino radical addition reaction to α,β-unsatur...
Scheme 3: Ir-catalyzed addition reactions of N-methyl-N-((trimethylsilyl)methyl)aniline (5) to 5,6-dihydro-2H...
Scheme 4: Ir-catalyzed addition reactions of N-methyl-N-((trimethylsilyl)methyl)aniline (5) to 2-cyclopenteno...
Scheme 5: Ir-catalyzed formation of tricyclic products 19 by a domino radical addition reaction to α,β-unsatu...
Scheme 6: Ir-catalyzed addition reactions of N-methyl-N-((trimethylsilyl)methyl)aniline (5) to α,β-unsaturate...
Scheme 7: Ir-catalyzed addition reactions of N-methyl-N-((trimethylsilyl)methyl)aniline (5) to α,β-unsaturate...
Scheme 8: Cyclization of putative radical A to intermediate B competes with reduction of A to form addition p...
Aqueous reductive amination using a dendritic metal catalyst in a dialysis bag
- Jorgen S. Willemsen,
- Jan C. M. van Hest and
- Floris P. J. T. Rutjes
Beilstein J. Org. Chem. 2013, 9, 960–965, doi:10.3762/bjoc.9.110
- examples, we decided to design a metallodendrimer that would show catalytic activity in a cascade process while compartmentalized under aqueous conditions. To this end, an iridium catalyst was selected that was known to be suitable for reductive amination in an aqueous environment. We showed that by
- catalyst can also be easily removed from the reaction mixture after the reaction has been completed (Figure 1). Results and Discussion To study this approach, we selected iridium catalyst 3, which has been previously successfully applied in aqueous reductive aminations [27]. The catalyst is based on
- related iridium complexes that are capable of performing transfer hydrogenation reactions, as has been documented by Fukuzumi et al. [28][29][30]. The water-soluble iridium catalyst 3 was prepared according to a procedure of Francis in high yield (Scheme 1) [27]. The starting material is [Cp*IrCl2]2 which
Graphical Abstract
Figure 1: General approach for the use of dendritic catalysts in a dialysis bag.
Scheme 1: Synthesis of water-soluble iridium catalyst 3.
Scheme 2: Synthesis of the desymmetrized bipyridine 8.
Scheme 3: Attachment of the adapted ligand 8 to the dendrimers via a multi-isocyanate coupling, followed by i...
Scheme 4: Catalytic reductive amination of valine (18) via unfavorable equilibrium reactions in water.
Figure 2: Formation of 19 catalyzed by the three iridium catalysts.
Figure 3: Reaction setup to perform compartmentalized catalysis.
Figure 4: G3 catalyst 16 activity in dialysis device.
Figure 5: G4 catalyst 17 activity in subsequent runs.
Flow photochemistry: Old light through new windows
- Jonathan P. Knowles,
- Luke D. Elliott and
- Kevin I. Booker-Milburn
Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229
Graphical Abstract
Figure 1: An immersion-well batch reactor with 125 W medium pressure Hg lamp.
Figure 2: Transmission profile of a 0.05 M solution, ε = 200 M−1 cm−1.
Figure 3: Schematic of a typical microflow photochemical reactor (above) and detail of a triple-channel micro...
Figure 4: Schematic of a typical macroflow photochemical reactor (above) and images of the FEP photochemical ...
Scheme 1: [2 + 2] photocycloadditions of enones with enol derivatives.
Scheme 2: Competing reactions in an intramolecular [2 + 2] photocycloaddition.
Scheme 3: Diastereocontrolled cycloaddition of a cyclic enone with cyclopentene.
Scheme 4: Comparison of yields and reaction times for a batch reactor with a microflow system.
Scheme 5: Intramolecular [2 + 2] photocycloaddition.
Scheme 6: Paterno–Büchi reaction of benzophenone with an allylic alcohol.
Scheme 7: Photooxygenation of cyclopentadiene.
Scheme 8: Preparation of the anthelmintic ascaridole 23.
Scheme 9: Production of rose oxide 27 from (−)-β-citronellol (24).
Scheme 10: Photocatalytic alkylation of benzylamine.
Scheme 11: Photocatalytic reduction of 4-nitroacetophenone.
Scheme 12: Conversion of L-lysine to L-pipecolinic acid.
Scheme 13: Photocatalytic hydrodehalogenation.
Scheme 14: Photocatalytic aza-Henry reactions.
Scheme 15: Photocatalytic α-alkylation of aliphatic ketones.
Scheme 16: Decarboxylative photochemical additions.
Scheme 17: Photochemical addition of isopropanol to furanones.
Scheme 18: Photochemical addition of methanol to limonene.
Scheme 19: Light-promoted reduction of flavone.
Scheme 20: Photoreduction of benzophenone with benzhydrol.
Scheme 21: Barton reaction in a microflow system.
Scheme 22: Microflow synthesis of vitamin D3.
Scheme 23: photochemical chlorination of cyclohexane.
Scheme 24: photochemical cyanation of pyrene.
Scheme 25: Intermolecular [2 + 2] cycloaddition of maleimide (76) and intramolecular [2 + 2] cycloaddition of ...
Scheme 26: Intramolecular [5 + 2] cycloaddition of maleimide under flow conditions.
Scheme 27: Intramolecular [5 + 2] cycloaddition as a key step in the synthesis of (±)-neostenine.
Scheme 28: In situ generation of a thioaldehyde by photolysis of a phenacyl sulfide.
Scheme 29: Photodimerisation of maleic anhydride.
Scheme 30: [2 + 2] cycloaddition of a chiral enone with ethylene.
Scheme 31: Intramolecular [2 + 2] cycloaddition of a cyclopentenone.
Scheme 32: Photochemical Wolff rearrangement and cyclisation to β-lactams.
Scheme 33: Photochemical rearrangement of aryl azides.
Scheme 34: Rearrangement of quinoline N-oxides to quinolones.
Scheme 35: Photochemical rearrangement of cyclobutenones.
Scheme 36: Photoisomerisation en route to a vitamin-D derivative.
Scheme 37: Schematic of the Seeberger photooxygenation apparatus and sensitised photooxygenation of citronello...
Scheme 38: Sensitised photooxygenation of dihydroartemisinic acid.
Scheme 39: Photochemical preparation of CpRu(MeCN)3PF6.
Scheme 40: In situ photochemical generation and reaction of a [CpRu]+ catalyst.
Scheme 41: Intermolecular alkene–alkyne coupling with photogenerated catalyst.
Scheme 42: PET deoxygenation of nucleosides.
Scheme 43: Photochemical defluorination of DABFT.
Scheme 44: Aromatic azide reduction by visible-light-mediated photocatalysis.
Scheme 45: Examples of visible-light-mediated reactions.
Scheme 46: Visible-light-mediated formation of iminium ions.
Scheme 47: Examples of visible-light-mediated photocatalytic reactions.
Scheme 48: Anhydride formation from a visible-light-mediated process.
Scheme 49: Light-mediated conjugate addition of glycosyl bromide 141 to acrolein.
Scheme 50: Visible-light-mediated photocyclisation to [5]helicene.
Iridium-catalyzed intramolecular [4 + 2] cycloadditions of alkynyl halides
- Andrew Tigchelaar and
- William Tam
Beilstein J. Org. Chem. 2012, 8, 1765–1770, doi:10.3762/bjoc.8.201
- –94%). These results are the first examples of cycloadditions of alkynyl halides using an iridium catalyst. Keywords: alkynyl halide; cycloaddition; diene-tethered alkyne; iridium; transition-metal catalyst; Introduction Iridium complexes have been used as catalysts for a wide variety of reactions
- substrates with a 4-atom tether. Optimization of iridium-catalyst for [4 + 2] cycloaddition of alkynyl bromide 1a. Optimization of solvent and temperature for the [IrCl(cod)]2/dppe-catalyzed [4 + 2] cycloaddition of 1a. [IrCl(cod)]2/dppe-catalyzed [4 + 2] cycloadditions of various alkynyl halides
Graphical Abstract
Scheme 1: Literature examples of intramolecular TMC [4 + 2] cycloadditions of diene-tethered alkynes.
Scheme 2: Reaction pathways of alkynyl halides in transition-metal-catalyzed reactions.
Scheme 3: Synthesis of diene-tethered alkynyl halides 1c and 1e.
Scheme 4: Synthesis of diene-tethered alkynyl halide 1g.
Scheme 5: Unsuccessful cycloaddition attempts with substrates with a 4-atom tether.
Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones
- Nicole Zimmermann,
- Robert Hilgraf,
- Lutz Lehmann,
- Daniel Ibarra and
- Wittko Francke
Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140
- chain at C5 through chelation. We chose Crabtree’s iridium catalyst ([Ir(cod)PCy3(py)]PF6) which has been reported to furnish excellent facial selectivities during directed hydrogenations of cyclic olefins [32][33][34]. Hydrogenation of acetate 16 in the presence of 11 mol % of Crabtree’s catalyst under
Graphical Abstract
Figure 1: Terpenoids 1–5 present in Alloxysta victrix and cis-fused bicyclic iridoids known from other insect...
Figure 2: 70 eV EI-mass spectrum of the iridoid X, a component of the volatile secretions of the parasitoid w...
Figure 3: Structures and gas chromatographic retention times of trans-fused dihydronepetalactones on a conven...
Scheme 1: Route from (S)-pulegone to the mixture of dihydronepetalactones a and b, consequently following Wol...
Figure 4: Configuration of the dihydronepetalactone a.
Figure 5: Route to stereochemically pure trans-fused dihydronepetalactones a–d from (R)-limonene.
Scheme 2: Synthesis of the key compound 16. Reaction conditions: a) O3, MeOH, −50 °C (86%); b) AcOH, piperidi...
Scheme 3: Synthesis of trans,trans-substituted dihydronepetalactone b. Reaction conditions: a) TBDMSCl, imida...
Figure 6: Configurations of compound 24 and the dihydronepetalactone b.
Scheme 4: Synthesis of cis,trans-substituted dihydronepetalactone c. Reaction conditions: a) Crabtree's catal...
Figure 7: Configurations of compound 26 and the dihydronepetalactone c.
Scheme 5: Synthesis of a 2:3 mixture of dihydronepetalactones c and d. Reaction conditions: a) (COCl)2, DMSO,...
Scheme 6: Formal synthesis of a mixture of dihydronepetalactones a and b from (R)-limonene.
Asymmetric Au-catalyzed cycloisomerization of 1,6-enynes: An entry to bicyclo[4.1.0]heptene
- Alexandre Pradal,
- Chung-Meng Chao,
- Patrick Y. Toullec and
- Véronique Michelet
Beilstein J. Org. Chem. 2011, 7, 1021–1029, doi:10.3762/bjoc.7.116
- chiral iridium catalyst [41] (Scheme 1, reaction 2). We and others recently pursued the improvement and development of this enantioselective process, by employing platinum [42][43][44], rhodium [45] or gold [46][47][48] complexes. Following our previous work with chiral gold catalysts [46], we report a
Graphical Abstract
Scheme 1: First reports on the racemic and asymmetric synthesis of bicyclo[4.1.0]heptenes.
Scheme 2: Synthesis of oxygen-tethered 1,6-enynes.
Scheme 3: Nitrogen-tethered 1,6-enynes.
Scheme 4: Synthesis of pentasubstituted bicyclic cyclopropanes.
Iridium-catalyzed asymmetric ring-opening reactions of oxabicyclic alkenes with secondary amine nucleophiles
- Dingqiao Yang,
- Ping Hu,
- Yuhua Long,
- Yujuan Wu,
- Heping Zeng,
- Hui Wang and
- Xiongjun Zuo
Beilstein J. Org. Chem. 2009, 5, No. 53, doi:10.3762/bjoc.5.53
- and 5 mol % bisphosphine ligand (S)-p-Tol-BINAP. The trans-configuration of 3f was confirmed by X-ray crystallography. Keywords: chiral bisphosphine ligand; iridium catalyst; oxabicyclic alkenes; ring-opening reaction; Introduction Substituted dihydronaphthalenes are important molecules with
- molecules with the dihydronaphthalene skeleton. Results and Discussion The ARO reaction involves many components of the chemical agents; we first attempted to optimize the ligand to iridium catalyst system (Scheme 1). In our initial experiments, we chose an achiral 1,1′-bis(diphenylphosphino)ferrocene (DPPF
- order of F
Graphical Abstract
Scheme 1: Identification of optimal chiral ligand for iridium-catalyzed asymmetric ring-opening of oxabenzono...
Figure 1: ORTEP plot for 3f.
Scheme 2: Proposed mechanism for the ARO of oxabenzonorbornadiene 1a with secondary amine nucleophiles.
