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Search for "Henry reaction" in Full Text gives 32 result(s) in Beilstein Journal of Organic Chemistry.
Red light excitation: illuminating photocatalysis in a new spectrum
- Lucas Fortier,
- Corentin Lefebvre and
- Norbert Hoffmann
Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22
- 40 has been proven to be the most efficient photocatalyst, promoting key transformations such as the aza-Henry reaction with 44 to give 45 under NIR light irradiation (Figure 6b). The reaction was found to critically depend on the presence of oxygen in the air for it to proceed. Through optimization
- and mechanistic investigations of the near-IR-photocatalyzed aza-Henry reaction, the authors have proposed either a single-electron transfer or an energy transfer mechanism. Additionally, the reaction displayed an unexpected sensitivity to the light wavelength used. Employing a higher-energy light
- heptamethin chain have been proven to be the most effective photocatalysts for accelerating the aza-Henry reaction. The differing reaction kinetics and tests with 9,10-dimethylanthracene suggest that a cooperative mechanism involving both single-electron transfer and singlet oxygen generation via energy
Graphical Abstract
Figure 1: Influence of the metal center M (Fe, Ru, Os) on the position of the MLCT and MC (metal-centered) ab...
Scheme 1: Red-light-mediated ring-closing metathesis through activation of a ruthenium catalyst by an osmium ...
Scheme 2: Photocatalyzed polymerization of dicylopentadiene mediated with red or blue light.
Figure 2: Comparison between [Ru(bpy)3]2+ and [Os(tpy)2]2+ in a photocatalyzed trifluoromethylation reaction:...
Scheme 3: Red-light photocatalyzed C–N cross-coupling reaction by T. Rovis et al. (SET = single-electron tran...
Figure 3: Red-light-mediated aryl oxidative addition with a bismuthinidene complex.
Scheme 4: Red-light-mediated reduction of aryl derivatives by O. S. Wenger et al. (PC = photocatalyst, anh = ...
Scheme 5: Red-light-mediated aryl halides reduction with an isoelectronic chromium complex (TDAE = tetrakis(d...
Scheme 6: Red-light-photocatalyzed trifluoromethylation of styrene derivatives with Umemoto’s reagent and a p...
Scheme 7: Red-light-mediated energy transfer for the cross-dehydrogenative coupling of N-phenyltetrahydroisoq...
Scheme 8: Red-light-mediated oxidative cyanation of tertiary amines with a phthalocyanin zinc complex.
Scheme 9: Formation of dialins and tetralins via a red-light-photocatalyzed reductive decarboxylation mediate...
Scheme 10: Oxidation of β-citronellol (28) via energy transfer mediated by a red-light activable silicon phtha...
Scheme 11: Formation of alcohol derivatives 32 from boron compounds 31 using chlorophyll (chl) as a red-light-...
Scheme 12: Red-light-driven reductive dehalogenation of α-halo ketones mediated by a thiaporphyrin photocataly...
Figure 4: Photoinduced electron transfer-reversible addition-fragmentation chain transfer polymerization medi...
Figure 5: Recent examples of red-light-mediated photocatalytic reactions with traditional organic dyes.
Figure 6: Squaraine photocatalysts used by Goddard et al. and aza-Henry reaction with squaraine-based photoca...
Figure 7: Reactions described by Goddard et al. involving 40 as the photocatalyst.
Figure 8: Various structures of squaraine derivatives used to initiate photopolymerizations.
Figure 9: Naturally occurring cyanins.
Figure 10: Influence of the structure on the photophysical properties of a cyanin dye.
Figure 11: NIR-light-mediated aza-Henry reaction photocatalyzed by 46.
Scheme 13: Photocatalyzed arylboronic acids oxidation by 46.
Figure 12: Cyanin structures synthetized and characterized by Goddard et al. (redox potentials given against s...
Figure 13: N,N′-Di-n-propyl-1,13-dimethoxyquinacridinium (55) with its redox potentials at its ground state an...
Scheme 14: Dual catalyzed C(sp2)–H arylation of 57 using DMQA 55 as the red-light-absorbing photocatalyst.
Scheme 15: Red-light-mediated aerobic oxidation of arylboronic acids 59 into phenols 60 via the use of DMQA as...
Figure 14: Red-light-photocatalyzed reactions proposed by Gianetti et al. using DMQA as the photocatalyst.
Scheme 16: Simultaneous release of NO and production of superoxide (O2•−) and their combination yielding the p...
Figure 15: Palladium porphyrin complex as the photoredox catalyst and the NO releasing substrate are linked in...
Scheme 17: Uncaging of compound 69 which is a microtubule depolymerizing agent using near IR irradiation. The ...
Scheme 18: Photochemical uncaging of drugs protected with a phenylboronic acid derivative using near IR irradi...
Scheme 19: Photoredox catalytical generation of aminyl radicals with near IR irradiation for the transfer of b...
Scheme 20: Photoredox catalytical fluoroalkylation of tryptophan moieties.
Figure 16: Simultaneous absorption of two photons of infrared light of low energy enables electronic excitatio...
Scheme 21: Uncaging Ca2+ ions using two-photon excitation with near infrared light.
Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives
- Jan Bartáček,
- Karel Chlumský,
- Jan Mrkvička,
- Lucie Paloušová,
- Miloš Sedlák and
- Pavel Drabina
Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62
- also tested in asymmetric aldol reactions. Under the optimised reaction conditions, aldol products with enantioselectivities of up to 91% ee were obtained. Keywords: asymmetric aldol reaction; asymmetric Henry reaction; chiral ligands; enantioselective catalysis; imidazolidine derivatives
- -enantiomer. A possible explanation of these results is illustrated in Figure 2, which shows plausible transition structures for the Henry reaction. Due to the Jahn–Teller effect, i.e., distortion of the octahedral Cu(II) complex forming four equatorial and two perpendicular coordination sites [18], the
- pyridine derivative [5] (see Supporting Information File 1, part S5); the ee values were overall high (74–92%), however, a little bit lower than those achieved by the complex of ligand IIIa (Δ 1–15% ee). Further, the copper(II) complex of ligand IV were also tested for asymmetric Henry reaction. The ligand
Graphical Abstract
Scheme 1: The preparation of 5-isopropyl-5-methyl-2-(pyridin-2-yl)imidazolidin-4-one derivatives and their ap...
Figure 1: The structure of newly designed ligands I–IV.
Figure 2: Plausible transition structures for the Henry reaction.
Switchable molecular tweezers: design and applications
- Pablo Msellem,
- Maksym Dekthiarenko,
- Nihal Hadj Seyd and
- Guillaume Vives
Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45
- reported tweezers 32 (Figure 17) incorporating chiral Cr(III)–salen arms for the allosteric regulation of a Henry reaction between benzaldehyde derivatives and nitromethane. In the closed form induced by K+ binding, high enantiomeric excesses around 90% and yields (<70%) were obtained due to the
Graphical Abstract
Figure 1: Principle of switchable molecular tweezers.
Figure 2: Principle of pH-switchable molecular tweezers 1 [19].
Figure 3: a) pH-Switchable tweezers 2 substituted with alkyl chains as switchable lipids. b) Schematic depict...
Figure 4: Modification of spectral properties of 3 by controlled induction of Pt–Pt interactions.
Figure 5: Conformational switching of di(hydroxyphenyl)pyrimidine-based tweezer 4 upon alkylation or fluoride...
Figure 6: Hydrazone-based pH-responsive tweezers 5 for mesogenic modulation.
Figure 7: pH-Switchable molecular tweezers 6 bearing acridinium moieties.
Figure 8: a) Terpyridine and pyridine-hydrazone-pyridine analogs molecular tweezers and b) extended pyridine ...
Figure 9: Terpyridine-based molecular tweezers with M–salphen arms and their field of application. Figure 9 was adapt...
Figure 10: a) Terpyridine-based molecular tweezers for diphosphate recognition [48]; b) bishelicene chiroptical te...
Figure 11: Terpyridine-based molecular tweezers with allosteric cooperative binding.
Figure 12: Terpyridine-based molecular tweezers presenting closed by default conformation.
Figure 13: Pyridine-pyrimidine-pyridine-based molecular tweezers.
Figure 14: Coordination-responsive molecular tweezers based on nitrogen-containing ligands.
Figure 15: Molecular tweezers exploiting the remote bipyridine or pyridine binding to trigger the conformation...
Figure 16: Bipyridine-based molecular tweezers exploiting the direct s-trans to s-cis-switching for a) anion b...
Figure 17: a) Podand-based molecular tweezers [66,67]. b) Application of tweezers 32 for the catalytic allosteric reg...
Figure 18: Anion-triggered molecular tweezers based on calix[4]pyrrole.
Figure 19: Anion-triggered molecular tweezers.
Figure 20: a) Principle of the weak link approach (WLA) developed by Mirkin and its application to b) symmetri...
Figure 21: Molecular tweezers as allosteric catalyst in asymmetric epoxide opening [80].
Figure 22: Allosteric regulation of catalytic activity in ring-opening polymerization with double tweezers 41.
Figure 23: a) Conformational switching of 42 by intramolecular –S–S– bridge formation. b) Shift of conformatio...
Figure 24: a) Redox-active glycoluril-TTF tweezers 44. b) Mechanism of stepwise oxidation of said tweezers wit...
Figure 25: Mechanism of formation of the mixed-valence dimers of tweezers 45.
Figure 26: Mechanism of carbohydrate liberation upon redox-mediated conformation switching of 46.
Figure 27: a) The encapsulation properties of 47 as well as the DCTNF release process from its host–guest comp...
Figure 28: Redox-active bipyridinium-based tweezers. a) With a ferrocenyl hinge 49, b) with a propyl hinge 50 ...
Figure 29: Redox-active calix[4]arene porphyrin molecular tweezers.
Figure 30: a) Mechanism of the three orthogonal stimuli. b) Cubic scheme showing the eight different states of ...
Figure 31: Redox-controlled molecular gripper based on a diquinone resorcin[4]arene.
Figure 32: a) Shinkai's butterfly tweezers and their different host–guest properties depending on the isomer. ...
Figure 33: Cyclam-tethered tweezers and their different host–guest complexes depending on their configuration.
Figure 34: Azobenzene-based catalytic tweezers.
Figure 35: Photoswitchable PIEZO channel mimic.
Figure 36: Stilbene-based porphyrin tweezers for fullerene recognition.
Figure 37: Stiff-stilbene-based tweezers with urea or thiourea functional units for a) anion binding, b) anion...
Figure 38: Feringa’s photoswitchable organocatalyst (a) and different catalyzed reactions with that system (b)....
Figure 39: a) Irie and Takeshita’s thioindigo-based molecular tweezers. b) Family of hemithioindigo-based mole...
Figure 40: Dithienylethylene crown ether-bearing molecular tweezers reported by Irie and co-workers.
Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates
- Hui Zheng,
- Ying Han,
- Jing Sun and
- Chao-Guo Yan
Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99
- furnished a chiral thiosquaramide-catalyzed tandem Michael–Henry reaction of phenacylmalononitriles and nitroolefins for the enantioselective synthesis of cyclopent-3-ene-1-carboxamides [32] (reaction 2 in Scheme 1). Mohanan and co-workers reported a PBu3-catalyzed [3 + 2] annulation of
Graphical Abstract
Scheme 1: Representative cycloaddition reactions of phenacylmalononitriles.
Figure 1: Single crystal structure of compound 3k.
Figure 2: Single crystal structure of compound 4a.
Figure 3: Single crystal structure of compound 4c.
Scheme 2: Proposed reaction mechanism for compounds 3, 4, and 5.
Figure 4: Single crystal structure of compound 5.
Scheme 3: Control experiment.
The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban
- Martin Vrbický,
- Karel Macek,
- Jaroslav Pochobradský,
- Jan Svoboda,
- Miloš Sedlák and
- Pavel Drabina
Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46
- of these drugs was studied in detail. Highly enantioselective catalysts were tested in the key step of the synthetic procedure, i.e., the asymmetric Henry reaction, under different reaction conditions, using several starting aldehydes. The corresponding nitroaldols as chiral intermediates in the
- syntheses of these drugs were obtained in high yields and enantiomeric excesses of up to 91% ee. Keywords: asymmetric Henry reaction; enantioselective catalysis; linezolid; oxazolidine-2-one derivatives; rivaroxaban; Introduction Oxazolidine-2-one derivatives represent an important branch of
- -1,2-diol, etc.) [11]. Beside this, approaches in which asymmetric synthesis is included are also applicable. Recently, the utilization of an asymmetric Henry reaction for the preparation of two oxazolidine-type drugs, namely linezolid (1) and rivaroxaban (2), has been described [12][13]. These
Graphical Abstract
Figure 1: The structure of the oxazolidine-2-one-containing drugs linezolid (1) and rivaroxaban (2).
Figure 2: Overview of the chiral ligands that were used for the study of the asymmetric Henry reaction.
Scheme 1: Syntheses of aldehydes 15–20.
Scheme 2: Synthesis of linezolid (1) and rivaroxaban (2) from nitroaldols 24 or 26.
The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids
- Marco Keller,
- Karl Sauvageot-Witzku,
- Franz Geisslinger,
- Nicole Urban,
- Michael Schaefer,
- Karin Bartel and
- Franz Bracher
Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183
- ethyl chloroformate/Et3N, followed by Wittig olefination with an ylide generated from (methoxymethyl)triphenylphosphonium chloride and LDA to give the enol ethers as E/Z mixtures. N-Phenethyl carbamates were obtained from benzaldehydes via Henry reaction with nitromethane, followed by zinc dust
Graphical Abstract
Figure 1: Prominent synthetic approaches to 1-benzyltetrahydroisoquinolines: Bischler–Napieralski, Pictet–Spe...
Figure 2: Structures of N-methylcoclaurine (1) and the ten 1-benzyl-1,2,3,4-tetrahydroisoquinoline alkaloids ...
Figure 3: Two routes using N- and O-alkoxycarbonylated building blocks for the synthesis of phenolic N-methyl...
Figure 4: Structures of the building blocks A1–A4 (N-ethoxycarbonyl phenethylamines) and B1–B3 (ω-methoxystyr...
Figure 5: Biological activity. Antiproliferative effects of the 1-benzyltetrahydroisoquinoline alkaloids in A...
N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts
- Viera Poláčková,
- Dominika Krištofíková,
- Boglárka Némethová,
- Renata Górová,
- Mária Mečiarová and
- Radovan Šebesta
Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176
- -Butanesulfinamide is highly useful in stereoselective synthesis as a stereoinducing group [21]. Thus, N-sulfinylureas and thioureas are a new class of organocatalysts, with the sulfinyl group acting both as an acidifying and a chiral controlling moiety. A variety of N-sulfinylureas catalyzed aza-Henry reaction
Graphical Abstract
Figure 1: Catalyst design principles.
Scheme 1: Synthesis of isothiocyanate 3a and isocyanate 3b.
Scheme 2: Synthesis of sulfinylthioureas C1 and ureas C2.
Scheme 3: Synthesis of adducts 8a,d,f in solution.
Figure 2: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) structures of catalyst (S,R) and (S,S)-C2, en...
Figure 3: a) Arrangements of reactants in the transition states; b) DFT-calculated (PBEh-3c/def2-SV(P)//M06-2...
Figure 4: DFT-calculated (PBEh-3c/def2-SV(P)//M06-2X/def2-TZVP) reaction profile for the Michael addition of ...
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
- desired material in essentially quantitative conversion within 1 hour of processing [126]. The flow output was connected to other apparatus to create a continuous multistep process for the preparation of the 8-formyl-7-hydroxycoumarin (94). The nitroaldol condensation (Henry reaction) is another important
- -cost [135]. These fibres are also suitable for flow systems as they can be easily shaped into the reactors. As an example, Tao’s group optimised several reactions in batch exploiting a quaternary ammonium functionalised PANF as catalyst (PANQAB-8F). They also reported the Henry reaction of 4
- understanding of the process itself [142][143][144]. Benaglia et al. exemplified 3D printing with a copper-catalysed Henry reaction [145]. Benzaldehyde (17) and the homogenous catalyst were mixed with nitroethane and the DIPEA base solution in a 1 mL polylactic acid (PLA) square-channelled microreactor. The
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.
Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst
- Jannis Ludwig,
- Julian Helberg,
- Hendrik Zipse and
- Rainer Herges
Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179
- switch the catalytic activity of the dimethylaminopyridine (DMAP) unit. DMAP is a known catalyst in the nitroaldol (Henry) reaction. Upon coordination to the Ni2+ ion, the basicity of the pyridine lone pair is attenuated and hence the catalytic activity is reduced. Decoordination restores the catalytic
- . reported on the photoswitching of the basicity of a piperidine nitrogen by reversible steric shielding of the nitrogen lone pair. The photoswitchable base was applied as a nucleophilic catalyst in the nitroaldol (Henry) reaction. Attached to a sterically demanding azobenzene unit, the lone pair was
- shielded in the cis configuration and therefore catalytically inactive. The basicity was restored by isomerization to the trans state leading to a rapid conversion to the β-nitroalcohol, the product of the Henry reaction [10][11][12]. We now present a photoswitchable catalyst whose basicity is controlled
Graphical Abstract
Figure 1: Basicity and nucleophilicity switching of the 4-(N,N-dimethylamino)pyridine “record player” molecul...
Scheme 1: Synthesis of 4-N,N-dimethylamino record player molecule 1 by Suzuki reaction between Ni-porphyrin p...
Figure 2: Composition of the different states of porphyrin 1 (1 mM) in the PSS at 530 nm and 435 nm, determin...
Figure 3: a) UV–vis cuvette with a solution of porphyrin 1 (13.1 µM in THF) and the corresponding UV–vis spec...
Scheme 2: General scheme of the nitroaldol (Henry) reaction that was used to investigate photoswitchable cata...
Scheme 3: DMAP (2), azopyridine trans-4, record player trans- and cis-1 and Ni-porphyrin 8 were used in kinet...
Figure 4: Conversion of 4-nitrobenzaldehyde (6) in the Henry reaction with nitroethane (5) as a function of t...
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...
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
- . In 2011, König and co-workers [150] demonstrated that eosin Y (OD13) was an efficient dye for an aza-Henry reaction [151], affording the tetrahydroquinolines 34.2 (Scheme 34). Simultaneously, the Tan group described the use of rose bengal (OD15) in the same transformation [152]. Regarding the strain
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...
New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions
- Iveta Chena Tichá,
- Simona Hybelbauerová and
- Jindřich Jindřich
Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80
- as the promoter (not in a catalytic amount) of a Henry reaction and obtained the product with 99% ee. Subsequently, Doyagüez et al. [17] attached L-proline to β-CD via different linkers (including a triazole linker) and used the resulting organocatalysts in an aldol reaction in water, albeit with a
Graphical Abstract
Figure 1: Schematic cone-shaped (a) and structure representations (b) of α-CD (six glucopyranoside units) and...
Figure 2: Common cinchona alkaloids (cinchonine, cinchonidine, quinine, quinidine).
Scheme 1: CuAAC click reaction of propargylated cinchona alkaloids 3a–d with 6I-azido-6I-deoxy-α-CD (1) and 6I...
Scheme 2: CuAAC click reaction of per-Me-N3-α-CD (6) or per-Me-N3-β-CD (7) and propargylated cinchona alkaloi...
Scheme 3: Synthesis of difunctionalized α-CD 11 with quinine moieties.
Figure 3: Representative 1H NMR spectrum of the non-methylated quinidine–α-CD derivative 4d.
Figure 4: Representative 13C NMR spectrum and parts of the HMBC spectrum of the non-methylated quinidine–α-CD...
Scheme 4: AAA reaction of MBH carbamate 12 catalyzed by the prepared CD derivatives 4a–d, 5a–d, 8a–d, 9a–d, 11...
Recent applications of chiral calixarenes in asymmetric catalysis
- Mustafa Durmaz,
- Erkan Halay and
- Selahattin Bozkurt
Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117
- reaction in the following order: phase-transfer catalysis, Henry reaction, Suzuki–Miyaura cross-coupling and Tsuji–Trost allylic substitution, hydrogenation, Michael addition, aldol and multicomponent Biginelli reactions, epoxidation, Meerwein−Ponndorf−Verley reduction, aza-Diels−Alder and epoxide ring
- investigated. Under optimized conditions, up to 47% ee was obtained by alkylation of 3 with 4-methylbenzyl bromide in the presence of 5 mol % catalyst 12. Henry reaction Since lower-rim functionalization of calix[4]arene is relatively easy, a variety of inherently chiral calix[4]arenes substituted at the lower
- important transformations: phase-transfer catalysis, Henry reaction, Suzuki–Miyaura cross-coupling and Tsuji–Trost allylic substitution, hydrogenation, Michael addition, aldol and multicomponent Biginelli reactions, epoxidation, Meerwein–Ponndorf–Verley reduction, aza-Diels–Alder and epoxide ring-opening
Graphical Abstract
Figure 1: Inherently chiral calix[4]arene-based phase-transfer catalysts.
Scheme 1: Asymmetric alkylations of 3 catalyzed by (±)-1 and (±)-2 under phase-transfer conditions.
Scheme 2: Synthesis of chiral calix[4]arene-based phase-transfer catalyst 7 and structure of O’Donnell’s N-be...
Scheme 3: Asymmetric alkylation of glycine derivative 3 catalyzed by calixarene-based phase-transfer catalyst ...
Figure 2: Calix[4]arene-amides used as phase-transfer catalysts.
Scheme 4: Phase-transfer alkylation of 3 catalyzed by calixarene-triamide 12.
Scheme 5: Synthesis of inherently chiral calix[4]arenes 20a/20b substituted at the lower rim. Reaction condit...
Scheme 6: Asymmetric Henry reaction between 21 and 22 catalyzed by 20a/20b.
Figure 3: Proposed transition state model of asymmetric Henry reaction.
Scheme 7: Synthesis of enantiomerically pure phosphinoferrocenyl-substituted calixarene ligands 27–29.
Scheme 8: Asymmetric coupling reaction of aryl boronates and aryl halides in the presence of calixarene mono ...
Scheme 9: Asymmetric allylic alkylation in the presence of calix[4]arene ligand (S,S)-29.
Figure 4: Structure of inherently chiral oxazoline calix[4]arenes applied in the palladium-catalyzed Tsuji–Tr...
Scheme 10: Asymmetric Tsuji–Trost reaction in the presence of calix[4]arene ligands 36–39.
Figure 5: BINOL-derived calix[4]arene-diphosphite ligands.
Scheme 11: Asymmetric hydrogenation of 41a and 41b catalyzed by in situ-generated catalysts comprised of [Rh(C...
Figure 6: Inherently chiral calix[4]arene 43 containing a diarylmethanol structure.
Scheme 12: Asymmetric Michael addition reaction of 44 with 45 catalyzed by 43.
Figure 7: Calix[4]arene-based chiral primary amine–thiourea catalysts.
Scheme 13: Asymmetric Michael addition of 48 with 49 catalyzed by 47a and 47b.
Scheme 14: Enantioselective Michael addition of 51 to 52 catalyzed by calix[4]arene thioureas.
Scheme 15: Synthesis of calix[4]arene-based tertiary amine–thioureas 54–56.
Scheme 16: Asymmetric Michael addition of 34 and 57 to nitroalkenes 49 catalyzed by 54b.
Scheme 17: Synthesis of p-tert-butylcalix[4]arene bis-squaramide derivative 64.
Scheme 18: Asymmetric Michael addition catalyzed by 64.
Scheme 19: Synthesis of chiral p-tert-butylphenol analogue 68.
Figure 8: Novel prolinamide organocatalysts based on the calix[4]arene scaffold.
Scheme 20: Asymmetric aldol reactions of 72 with 70 and 71 catalyzed by 69b.
Scheme 21: Synthesis of p-tert-butylcalix[4]arene-based chiral organocatalysts 75 and 78 derived from L-prolin...
Scheme 22: Synthesis of upper rim-functionalized calix[4]arene-based L-proline derivative 83.
Scheme 23: Synthesis and proposed structure of Calix-Pro-MN (86).
Figure 9: Calix[4]arene-based L-proline catalysts containing ester, amide and acid units.
Scheme 24: Synthesis of calix[4]arene-based prolinamide 92.
Scheme 25: Calixarene-based catalysts for the aldol reaction of 21 with 70.
Scheme 26: Asymmetric aldol reactions of 72 with cyclic ketones catalyzed by calix[4]arene-based chiral organo...
Figure 10: A proposed structure for catalyst 92 in H2O.
Scheme 27: Synthetic route for organocatalyst 98.
Scheme 28: Asymmetric aldol reactions catalyzed by 99.
Figure 11: Proposed catalytic environment for catalyst 99 in the presence of water.
Scheme 29: Asymmetric aldol reactions between 94 and 72 catalyzed by 55a.
Scheme 30: Enantioselective Biginelli reactions catalyzed by 69f.
Scheme 31: Synthesis of calix[4]arene–(salen) complexes.
Scheme 32: Enantioselective epoxidation of 108 catalyzed by 107a/107b.
Scheme 33: Synthesis of inherently chiral calix[4]arene catalysts 111 and 112.
Scheme 34: Enantioselective MPV reduction.
Scheme 35: Synthesis of chiral calix[4]arene ligands 116a–c.
Scheme 36: Asymmetric MPV reduction with chiral calix[4]arene ligands.
Scheme 37: Chiral AlIII–calixarene complexes bearing distally positioned chiral substituents.
Scheme 38: Asymmetric MPV reduction in the presence of chiral calix[4]arene diphosphites.
Scheme 39: Synthesis of enantiomerically pure inherently chiral calix[4]arene phosphonic acid.
Scheme 40: Asymmetric aza-Diels–Alder reactions catalyzed by (cR,pR)-121.
Scheme 41: Asymmetric ring opening of epoxides catalyzed by (cR,pR)-121.
Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines
- Hélène Pellissier
Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114
- -Henry reactions The catalytic asymmetric Henry reaction, also known as catalytic asymmetric nitroaldol reaction, constitutes a useful synthetic methodology towards chiral β-nitro alcohols [69][70]. This reaction and related aza-Henry reactions involving imines have been promoted by both metal catalysts
- cinchona alkaloid-derived thiourea. Aza-Henry reaction of N-Boc-isatin imines with nitromethane catalyzed by a bifunctional guanidine. Domino addition/cyclization reaction of N-Boc-isatin imines with 1,4-dithiane-2,5-diol (53) catalyzed by a tertiary amine-squaramide. Nickel-catalyzed additions of methanol
Graphical Abstract
Scheme 1: Mannich reaction of N-Boc-isatin imines with ethyl nitroacetate (2) catalyzed by a cinchona alkaloi...
Scheme 2: Mannich reaction of N-Boc-isatin imines with 1,3-dicarbonyl compounds catalyzed by a cinchona alkal...
Scheme 3: Mannich reaction of N-alkoxycarbonylisatin imines with acetylacetone catalyzed by a cinchona alkalo...
Scheme 4: Mannich reaction of isatin-derived benzhydrylketimines with trimethylsiloxyfuran catalyzed by a pho...
Scheme 5: Mannich reaction of N-Boc-isatin imines with acetaldehyde catalyzed by a primary amine.
Scheme 6: Mannich reaction of N-Cbz-isatin imines with aldehydes catalyzed by L-diphenylprolinol trimethylsil...
Scheme 7: Addition of dimedone-derived enaminones to N-Boc-isatin imines catalyzed by a phosphoric acid.
Scheme 8: Addition of hydroxyfuran-2-one-derived enaminones to N-Boc-isatin imines catalyzed by a phosphoric ...
Scheme 9: Zinc-catalyzed Mannich reaction of N-Boc-isatin imines with silyl ketene imines.
Scheme 10: Tin-catalyzed Mannich reaction of N-arylisatin imines with an alkenyl trichloroacetate.
Scheme 11: Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with acrolein catalyzed by β-isocupreidin...
Scheme 12: Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with acrolein (35) catalyzed by α-isocupr...
Scheme 13: Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with maleimides catalyzed by β-isocupreid...
Scheme 14: Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with nitroolefins catalyzed by a cinchona...
Scheme 15: Friedel–Crafts reactions of N-Boc-isatin imines with 1 and 2-naphthols catalyzed by a cinchona alka...
Scheme 16: Friedel–Crafts reactions of N-alkoxycarbonyl-isatin imines with 1 and 2-naphthols catalyzed by a ci...
Scheme 17: Friedel–Crafts reaction of N-Boc-isatin imines with 6-hydroxyquinolines catalyzed by a cinchona alk...
Scheme 18: Aza-Henry reaction of N-Boc-isatin imines with nitromethane catalyzed by a bifunctional guanidine.
Scheme 19: Domino addition/cyclization reaction of N-Boc-isatin imines with 1,4-dithiane-2,5-diol (53) catalyz...
Scheme 20: Nickel-catalyzed additions of methanol and cumene hydroperoxide to N-Boc-isatin imines.
Scheme 21: Palladium-catalyzed addition of arylboronic acids to N-tert-butylsulfonylisatin imines.
Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions
- Yonglei Du,
- Jian Li,
- Kerong Chen,
- Chenglin Wu,
- Yu Zhou and
- Hong Liu
Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131
- addition, the electrophilicity of the reacting carbon center of nitrovinylacetamide is likely enhanced by H-bonding, thereby enabling the Michael addition to construct a unique quaternary stereogenic center complex A which would cyclize concurrently via Henry reaction to give the product 3 and regenerates
Graphical Abstract
Figure 1: Representative spirooxindole natural products.
Scheme 1: Construction of spirocyclopentaneoxindole scaffolds.
Scheme 2: Scope of enantioselective synthesis of spirooxindoles. Reaction conditions: catalyst d (0.01 mmol),...
Scheme 3: A plausible mechanism.
Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction
- Yan Chen,
- Xiaoman Wang,
- Junchang Wang and
- You Yang
Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79
- chain elongations of aldoses employing the Henry reaction, the aldol reaction, and the Wittig reaction for the preparation of ketoheptoses [20][21][22], sugar lactones were also often utilized for the synthesis of D-manno-heptulose via reactions with C-nucleophiles or conversion into exocyclic glycals
Graphical Abstract
Scheme 1: Retrosynthetic analysis of D-manno-heptulose.
Scheme 2: Initial attempt on the synthesis of the C4 aldehyde from D-lyxose (5).
Scheme 3: Synthesis of differentially protected ketoheptose building block 2.
Scheme 4: Synthesis of D-manno-heptulose (1).
Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions
- José M. Andrés,
- Miriam Ceballos,
- Alicia Maestro,
- Isabel Sanz and
- Rafael Pedrosa
Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61
- organocatalysts in the stereoselective aza-Henry reaction [31]. Now we describe the results obtained in different stereoselective nitro-Michael additions promoted by these materials. Results and Discussion The ability of the supported catalysts (II–V) to promote the stereoselective nitro-Michael reaction was
Graphical Abstract
Figure 1: Parent and supported bifunctional thioureas used in this work.
Scheme 1: Reaction of nitrostyrene with diethyl malonate and 2-ethoxycarbonyl cyclopentanone.
Scheme 2: Reaction of nitrostyrenes with malonates and β-diketones.
Scheme 3: Reaction of nitrostyrenes with β-keto esters and β-dicarbonyl compounds.
Scheme 4: Reaction of nitrostyrenes with α-nitrocyclohexanone and ethyl α-nitropropionate.
The aminoindanol core as a key scaffold in bifunctional organocatalysts
- Isaac G. Sonsona,
- Eugenia Marqués-López and
- Raquel P. Herrera
Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50
- through an organocatalyzed asymmetric domino-Michael addition/Henry reaction (Scheme 8) [36]. These heterocyclic products are important chiral building blocks for the synthesis of organocatalytic frameworks and ligands for chiral metal complexes, both with the potential ability to induce chirality. They
- activate the 1,3-dicarbonyl compound 36 (Scheme 15). We would like to remark that although the authors indicated that the S enantiomer is obtained in their final products, they depicted the R configuration, as is drawn in the Scheme 15. Aza-Henry reaction Ellman’s group designed a set of pioneering (thio
- state TS10 proposed for the asymmetric addition of dialkylhydrazone 28 to the β,γ-unsaturated α-ketoesters 26 catalyzed by ent-4. Results for the aza-Henry reaction carried out with the structurally modified catalysts 50–50''. Asymmetric F–C alkylation catalyzed by thiourea 4. Asymmetric F–C alkylation
Graphical Abstract
Figure 1: Different configurations of 1,2-aminoindanol 1a–d.
Scheme 1: Asymmetric F–C alkylation catalyzed by thiourea 4.
Figure 2: Results for the F–C reaction carried out with catalyst 4 and the structurally modified analogues, 4'...
Figure 3: (a) Transition state TS1 originally proposed for the F–C reaction catalyzed by thiourea 4 [18]. (b) Tra...
Scheme 2: Asymmetric F–C alkylation catalyzed by thiourea ent-4 in the presence of D-mandelic acid as a Brøns...
Figure 4: Transition state TS2 proposed for the activation of the thiourea-based catalyst ent-4 by an externa...
Scheme 3: Friedel–Crafts alkylation of indoles catalyzed by the chiral thioamide 6.
Scheme 4: Scalable tandem C2/C3-annulation of indoles, catalyzed by the thioamide ent-6.
Scheme 5: Plausible tandem process mechanism for the sequential, double Friedel–Crafts alkylation, which invo...
Scheme 6: One-pot multisequence process that allows the synthesis of interesting compounds 14. The pharmacolo...
Scheme 7: Reaction pathway proposed for the preparation of the compounds 14.
Scheme 8: The enantioselective synthesis of cis-vicinal-substituted indane scaffolds 21, catalyzed by ent-6.
Scheme 9: Asymmetric domino procedure (Michael addition/Henry cyclization), catalyzed by the thioamide ent-6 ...
Scheme 10: The enantioselective addition of indoles 2 to α,β-unsaturated acyl phosphonates 24, a) screening of...
Figure 5: Proposed transition state TS7 for the Friedel–Crafts reaction of indole and α,β-unsaturated acyl ph...
Scheme 11: Study of aliphatic β,γ-unsaturated α-ketoesters 26 as substrates in the F–C alkylation of indoles c...
Figure 6: Possible transition states TS8 and TS9 in the asymmetric addition of indoles 2 to the β,γ-unsaturat...
Figure 7: Transition state TS10 proposed for the asymmetric addition of dialkylhydrazone 28 to the β,γ-unsatu...
Scheme 12: Different β-hydroxylamino-based catalysts tested in a Michael addition, and the transition state TS...
Scheme 13: Enantioselective addition of acetylacetone (36a) to nitroalkenes 3, catalyzed by 37 and the propose...
Scheme 14: Addition of 3-oxindoles 39 to 2-amino-1-nitroethenes 40, catalyzed by 41.
Scheme 15: Michael addition of 1,3-dicarbonyl compounds 36 to the nitroalkenes 3 catalyzed by the squaramide 43...
Scheme 16: Asymmetric aza-Henry reaction catalyzed by the aminoindanol-derived sulfinyl urea 50.
Figure 8: Results for the aza-Henry reaction carried out with the structurally modified catalysts 50–50''.
Scheme 17: Diels–Alder reaction catalyzed by the aminoindanol derivative ent-41.
Scheme 18: Asymmetric Michael addition of 3-pentanone (55a) to the nitroalkenes 3 through aminocatalysis.
Scheme 19: Substrate scope extension for the asymmetric Michael addition between the ketones 55 and the nitroa...
Scheme 20: A possible reaction pathway in the presence of the catalyst 56 and the plausible transition state T...
(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers
- Giorgos Koutoulogenis,
- Nikolaos Kaplaneris and
- Christoforos G. Kokotos
Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48
- enantioselective domino-Michael–Henry reaction catalyzed by a secondary amine-thiourea between cyclohexa-1,4-dienone (44) and a γ,δ-alkyl-aryl-disubstituted nitrodiene 45, providing bicyclo[3.2.1]octan-2-one 46 (Scheme 16) [26]. The organocatalyst used in this reaction is the cyclic thiourea 47. It is noted, that
- organocatalyst 47 affords products only in organic solvents and more specifically in THF. This tandem Michael–Henry reaction provided the product in an excellent yield of 91%, excellent enantiomeric excess of 96% and complete diastereocontrol. Trying to provide a greener alternative, Kokotos and co-workers
- , catalyzed the same tandem Michael–Henry reaction between cyclohexa-1,4-dienone (44) and nitrodiene 48 by employing the secondary amine-thiourea 50, which contains a fluorine on its skeleton and 4-nitrobenzoic acid as a cocatalyst, to provide the substituted bicyclo[3.2.1]octan-2-one 49 (Scheme 17) [27]. It
Graphical Abstract
Scheme 1: Activation of carbonyl compounds via enamine and iminium intermediates [2].
Scheme 2: Electronic and steric interactions present in enamine activation mode [2].
Scheme 3: Electrophilic activation of carbonyl compounds by a thiourea moiety.
Scheme 4: Asymmetric synthesis of dihydro-2H-pyran-6-carboxylate 3 using organocatalyst 4 [16].
Scheme 5: Possible hydrogen-bonding for the reaction of (E)-methyl 2-oxo-4-phenylbut-3-enoate [16].
Scheme 6: Asymmetric desymmetrization of 4,4-cyclohexadienones using the Michael addition reaction with malon...
Scheme 7: The enantioselective synthesis of α,α-disubstituted cycloalkanones using catalyst 11 [18].
Scheme 8: The enantioselective synthesis of indolo- and benzoquinolidine compounds through aza-Diels–Alder re...
Scheme 9: Enantioselective [5 + 2] cycloaddition [20].
Scheme 10: Asymmetric synthesis of oxazine derivatives 26 [21].
Scheme 11: Asymmetric synthesis of bicyclo[3.3.1]nonadienone, core 30 present in (−)-huperzine [22].
Scheme 12: Asymmetric inverse electron-demand Diels-Alder reaction catalyzed by amine-thiourea 34 [23].
Scheme 13: Asymmetric entry to morphan skeletons, catalyzed by amine-thiourea 37 [24].
Scheme 14: Asymmetric transformation of (E)-2-nitroallyl acetate [25].
Scheme 15: Proposed way of activation.
Scheme 16: Asymmetric synthesis of nitrobicyclo[3.2.1]octan-2-one derivatives [26].
Scheme 17: Asymmetric tandem Michael–Henry reaction catalyzed by 50 [27].
Scheme 18: Asymmetric Diels–Alder reactions of 3-vinylindoles 51 [29].
Scheme 19: Proposed transition state and activation mode of the asymmetric Diels–Alder reactions of 3-vinylind...
Scheme 20: Desymmetrization of meso-anhydrides by Chin, Song and co-workers [30].
Scheme 21: Desymmetrization of meso-anhydrides by Connon and co-workers [31].
Scheme 22: Asymmetric intramolecular Michael reaction [32].
Scheme 23: Asymmetric addition of malonate to 3-nitro-2H-chromenes 67 [33].
Scheme 24: Intramolecular desymmetrization through an intramolecular aza-Michael reaction [34].
Scheme 25: Enantioselective synthesis of (−)-mesembrine [34].
Scheme 26: A novel asymmetric Michael–Michael reaction [35].
Scheme 27: Asymmetric three-component reaction catalyzed by Takemoto’s catalyst 77 [46].
Scheme 28: Asymmetric domino Michael–Henry reaction [47].
Scheme 29: Asymmetric domino Michael–Henry reaction [48].
Scheme 30: Enantioselective synthesis of derivatives of 3,4-dihydro-2H-pyran 89 [49].
Scheme 31: Asymmetric addition of α,α-dicyano olefins 90 to 3-nitro-2H-chromenes 91 [50].
Scheme 32: Asymmetric three-component reaction producing 2,6-diazabicyclo[2.2.2]octanones 95 [51].
Scheme 33: Asymmetric double Michael reaction producing substituted chromans 99 [52].
Scheme 34: Enantioselective synthesis of multi-functionalized spiro oxindole dienes 106 [53].
Scheme 35: Organocatalyzed Michael aldol cyclization [54].
Scheme 36: Asymmetric synthesis of dihydrocoumarins [55].
Scheme 37: Asymmetric double Michael reaction en route to tetrasubstituted cyclohexenols [56].
Scheme 38: Asymmetric synthesis of α-trifluoromethyl-dihydropyrans 121 [58].
Scheme 39: Tyrosine-derived tertiary amino-thiourea 123 catalyzed Michael hemiaketalization reaction [59].
Scheme 40: Enantioselective entry to bicyclo[3.2.1]octane unit [60].
Scheme 41: Asymmetric synthesis of spiro[4-cyclohexanone-1,3’-oxindoline] 126 [61].
Scheme 42: Kinetic resolution of 3-nitro-2H-chromene 130 [62].
Scheme 43: Asymmetric synthesis of chromanes 136 [63].
Scheme 44: Wang’s utilization of β-unsaturated α-ketoesters 87 [64,65].
Scheme 45: Asymmetric entry to trifluoromethyl-substituted dihydropyrans 144 [66].
Scheme 46: Phenylalanine-derived thiourea-catalyzed domino Michael hemiaketalization reaction [67].
Scheme 47: Asymmetric synthesis of α-trichloromethyldihydropyrans 149 [68].
Scheme 48: Takemoto’s thiourea-catalyzed domino Michael hemiaketalization reaction [69].
Scheme 49: Asymmetric synthesis of densely substituted cyclohexanes [70].
Scheme 50: Enantioselective synthesis of polysubstituted chromeno [4,3-b]pyrrolidine derivatines 157 [71].
Scheme 51: Enantioselective synthesis of spiro-fused cyclohexanone/5-oxazolone scaffolds 162 [72].
Scheme 52: Utilizing 2-mercaptobenzaldehydes 163 in cascade processes [73,74].
Scheme 53: Proposed transition state of the initial sulfa-Michael step [74].
Scheme 54: Asymmetric thiochroman synthesis via dynamic kinetic resolution [75].
Scheme 55: Enantioselective synthesis of thiochromans [76].
Scheme 56: Enantioselective synthesis of chromans and thiochromans synthesis [77].
Scheme 57: Enantioselective sulfa-Michael aldol reaction en route to spiro compounds [78].
Scheme 58: Enantioselective synthesis of 4-aminobenzo(thio)pyrans 179 [79].
Scheme 59: Asymmetric synthesis of tetrahydroquinolines [80].
Scheme 60: Novel asymmetric Mannich–Michael sequence producing tetrahydroquinolines 186 [81].
Scheme 61: Enantioselective synthesis of biologically interesting chromanes 190 and 191 [82].
Scheme 62: Asymmetric tandem Henry–Michael reaction [83].
Scheme 63: An asymmetric synthesis of substituted cyclohexanes via a dynamic kinetic resolution [84].
Scheme 64: Three component-organocascade initiated by Knoevenagel reaction [85].
Scheme 65: Asymmetric Michael reaction catalyzed by catalysts 57 and 211 [86].
Scheme 66: Proposed mechanism for the asymmetric Michael reaction catalyzed by catalysts 57 and 211 [86].
Scheme 67: Asymmetric facile synthesis of hexasubstituted cyclohexanes [87].
Scheme 68: Dual activation catalytic mechanism [87].
Scheme 69: Asymmetric Michael–Michael/aldol reaction catalyzed by catalysts 57, 219 and 214 [88].
Scheme 70: Asymmetric synthesis of substituted cyclohexane derivatives, using catalysts 57 and 223 [89].
Scheme 71: Asymmetric synthesis of substituted piperidine derivatives, using catalysts 223 and 228 [90].
Scheme 72: Asymmetric synthesis of endo-exo spiro-dihydropyran-oxindole derivatives catalyzed by catalyst 232 [91]....
Scheme 73: Asymmetric synthesis of carbazole spiroxindole derivatives, using catalyst 236 [92].
Scheme 74: Enantioselective formal [2 + 2] cycloaddition of enal 209 with nitroalkene 210, using catalysts 23 ...
Scheme 75: Asymmetric synthesis of polycyclized hydroxylactams derivatives, using catalyst 242 [94].
Scheme 76: Asymmetric synthesis of product 243, using catalyst 246 [95].
Scheme 77: Formation of the α-stereoselective acetals 248 from the corresponding enol ether 247, using catalys...
Scheme 78: Selective glycosidation, catalyzed by Shreiner’s catalyst 23 [97].
Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts
- Laura A. Bryant,
- Rossana Fanelli and
- Alexander J. A. Cobb
Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46
- set up a 4π-electrocyclization, generating second intermediate 27. Elimination of the tertiary amine then gives γ-methylene cyclopentenone 28. 1,2-Addition reactions Henry reaction The use of cupreine and cupreidine derivatives in the addition of nitroalkanes to carbonyl compounds was first
Graphical Abstract
Figure 1: The structural diversity of the cinchona alkaloids, along with cupreine, cupreidine, β-isoquinidine...
Scheme 1: The original 6’-OH cinchona alkaloid organocatalytic MBH process, showing how the free 6’-OH is ess...
Scheme 2: Use of β-ICPD in an aza-MBH reaction.
Scheme 3: (a) The isatin motif is a common feature for MBH processes catalyzed by β-ICPD, as demonstrated by ...
Scheme 4: (a) Chen’s asymmetric MBH reaction. Good selectivity was dependent upon the presence of (R)-BINOL (...
Scheme 5: Lu and co-workers synthesis of a spiroxindole.
Scheme 6: Kesavan and co-workers’ synthesis of spiroxindoles.
Scheme 7: Frontier’s Nazarov cyclization catalyzed by β-ICPD.
Scheme 8: The first asymmetric nitroaldol process catalyzed by a 6’-OH cinchona alkaloid.
Scheme 9: A cupreidine derived catalyst induces a dynamic kinetic asymmetric transformation.
Scheme 10: Cupreine derivative 38 has been used in an organocatalytic asymmetric Friedel–Crafts reaction.
Scheme 11: Examples of 6’-OH cinchona alkaloid catalyzed processes include: (a) Deng’s addition of dimethyl ma...
Scheme 12: A diastereodivergent sulfa-Michael addition developed by Melchiorre and co-workers.
Scheme 13: Melchiorre’s vinylogous Michael addition.
Scheme 14: Simpkins’s TKP conjugate addition reactions.
Scheme 15: Hydrocupreine catalyst HCPN-59 can be used in an asymmetric cyclopropanation.
Scheme 16: The hydrocupreine and hydrocupreidine-based catalysts HCPN-65 and HCPD-67 demonstrate the potential...
Scheme 17: Jørgensen’s oxaziridination.
Scheme 18: Zhou’s α-amination using β-ICPD.
Scheme 19: Meng’s cupreidine catalyzed α-hydroxylation.
Scheme 20: Shi’s biomimetic transamination process for the synthesis of α-amino acids.
Scheme 21: β-Isocupreidine catalyzed [4 + 2] cycloadditions.
Scheme 22: β-Isocupreidine catalyzed [2+2] cycloaddition.
Scheme 23: A domino reaction catalyst by cupreidine catalyst CPD-30.
Scheme 24: (a) Dixon’s 6’-OH cinchona alkaloid catalyzed oxidative coupling. (b) An asymmetric oxidative coupl...
Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors
- Ming-Liang Zhang,
- Deng-Feng Yue,
- Zhen-Hua Wang,
- Yuan Luo,
- Xiao-Ying Xu,
- Xiao-Mei Zhang and
- Wei-Cheng Yuan
Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31
- 100049, China 10.3762/bjoc.12.31 Abstract For the first time, a catalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones was achieved with a chiral bifunctional amine-thiourea as a catalyst possessing multiple hydrogen-bond donors. With this developed method, a range of 3-hydroxy-3-nitromethyl-1H
- -pyrrol-2(3H)-ones bearing quaternary stereocenters were obtained in acceptable yield (up to 75%) and enantioselectivity (up to 73% ee). Keywords: asymmetric catalysis; bifunctional catalysts; Henry reaction; organocatalysis; 1H-pyrrole-2,3-diones; Introduction Asymmetric organocatalysis has been
- successfully used as chiral organocatalysts for the asymmetric Michael addition and Mannich reactions [12][13][14]. Meanwhile, the Henry reaction is one of the most important carbon–carbon bond-forming reactions that provides straightforward access to β-nitroalcohols, which can be further transformed into
Graphical Abstract
Scheme 1: The strategy to construct chiral 3-substituted-3-hydroxy-1H-pyrrol-2(3H)-ones.
Figure 1: The X-ray structure of compound 4i.
Figure 2: A proposed transition state for the asymmetric Henry reaction.
Organocatalytic and enantioselective Michael reaction between α-nitroesters and nitroalkenes. Syn/anti-selectivity control using catalysts with the same absolute backbone chirality
- Jose I. Martínez,
- Uxue Uria,
- Maria Muñiz,
- Efraím Reyes,
- Luisa Carrillo and
- Jose L. Vicario
Beilstein J. Org. Chem. 2015, 11, 2577–2583, doi:10.3762/bjoc.11.277
- cyclohexanediamine/squaramide catalyst 6 which, as mentioned before, is based on a chiral backbone with the same absolute chirality as 4. The reaction conditions used for this reaction were those already observed to be optimal in our previous work for the cascade Michael/Henry reaction using this catalyst, that
Graphical Abstract
Scheme 1: Diastereodivergent cascade Michael/Michael reaction using catalysts with the same absolute chiralit...
Scheme 2: Diastereodivergent enantioselective Michael reaction using ethyl 2-nitropropanoate and β-nitrostyre...
Figure 1: ORTEP diagrams for anti-3a and syn-3o respectively.
Scheme 3: Proposed models to explain the stereochemical outcome of the reaction.
The chemistry of amine radical cations produced by visible light photoredox catalysis
- Jie Hu,
- Jiang Wang,
- Theresa H. Nguyen and
- Nan Zheng
Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234
- coworkers reported a visible light-mediated aza-Henry reaction that harnesses the synthetic potential of iminium ions. Using only 1 mol % of [Ir(ppy)2(dtbbpy)](PF6) and visible light, a variety of N-aryltetrahydroisoquinolines were oxidatively coupled with nitroalkanes to provide the aza-Henry products in
- . König and coworkers showed that the same aza-Henry reaction can be catalyzed by the organic dye Eosin Y to afford the aza-Henry product 18 (Scheme 5) [67]. In addition to nitroalkanes, dialkyl malonates and malononitrile can be used as pronucleophiles to provide β-diester amine 19 and α-aminonitrile 20
- . The authors proposed a mechanism similar to that proposed by Stephenson and coworkers for the aza-Henry reaction catalyzed by the Ir complex (Scheme 3). The Tan group simultaneously reported that another organic dye, Rose Bengal (RB), can be used in place of Eosin Y to catalyze the aza-Henry reaction
Graphical Abstract
Scheme 1: Amine radical cations’ mode of reactivity.
Scheme 2: Reductive quenching of photoexcited Ru complexes by Et3N.
Scheme 3: Photoredox aza-Henry reaction.
Scheme 4: Formation of iminium ions using BrCCl3 as stoichiometric oxidant.
Scheme 5: Oxidative functionalization of N-aryltetrahydroisoquinolines using Eosin Y.
Scheme 6: Synthetic and mechanistic studies of Eosin Y-catalyzed aza-Henry reaction.
Scheme 7: Oxidative functionalization of N-aryltetrahydroisoquinolines using RB and GO.
Scheme 8: Merging Ru-based photoredox catalysis and Lewis base catalysis for the Mannich reaction.
Scheme 9: Merging Au-based photoredox catalysis and Lewis base catalysis for the Mannich reaction.
Scheme 10: Merging Ru-based photoredox catalysis and Cu-catalyzed alkynylation reaction.
Scheme 11: Merging Ru-based photoredox catalysis and NHC catalysis.
Scheme 12: 1,3-Dipolar cycloaddition of photogenically formed azomethine ylides.
Scheme 13: Plausible mechanism for photoredox 1,3-dipolar cycloaddition.
Scheme 14: Photoredox-catalyzed cascade reaction for the synthesis of fused isoxazolidines.
Scheme 15: Plausible mechanism for the photoredox-catalyzed cascade reaction.
Scheme 16: Photoredox-catalyzed α-arylation of glycine derivatives.
Scheme 17: Photoredox-catalyzed α-arylation of amides.
Scheme 18: Intramolecular interception of iminium ions by sulfonamides.
Scheme 19: Intramolecular interception of iminium ions by alcohols and sulfonamides.
Scheme 20: Intermolecular interception of iminium ions by phosphites.
Scheme 21: Photoredox-catalyzed oxidative phosphonylation by Eosin Y.
Scheme 22: Conjugated addition of α-amino radicals to Michael acceptors.
Scheme 23: Conjugated addition of α-amino radicals to Michael acceptors assisted by a Brønsted acid.
Scheme 24: Conjugated addition of α-amino radicals derived from anilines to Michael acceptors.
Scheme 25: Oxygen switch between two pathways involving α-amino radicals.
Scheme 26: Interception of α-amino radicals by azodicarboxylates.
Scheme 27: α-Arylation of amines.
Scheme 28: Plausible mechanism for α-arylation of amines.
Scheme 29: Photoinduced C–C bond cleavage of tertiary amines.
Scheme 30: Photoredox cleavage of C–C bonds of 1,2-diamines.
Scheme 31: Proposed mechanism photoredox cleavage of C–C bonds.
Scheme 32: Intermolecular [3 + 2] annulation of cyclopropylamines with olefins.
Scheme 33: Proposed mechanism for intermolecular [3 + 2] annulation.
Scheme 34: Photoinduced clevage of N–N bonds of aromatic hydrazines and hydrazides.
Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step
- James C. Anderson,
- Andreas S. Kalogirou,
- Michael J. Porter and
- Graham J. Tizzard
Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200
- ; Introduction The nitro-Mannich reaction (or aza-Henry reaction) has been developed to a standard where the product β-nitroamines 1 are now privileged building blocks. In part this is due to the complementary synthetic flexibility available from the two different nitrogen atom oxidation states (Scheme 1) [1
- available from a Henry reaction [50], imine 14 from the condensation of p-anisidine and isobutyraldehyde, and the process can easily be made asymmetric [45]. Conjugate addition of hydride to 13 and subsequent trapping of the nitronate anion with freshly prepared imine 14 in THF gave β-nitroamine 15 in 64
Graphical Abstract
Scheme 1: Schematic nitro-Mannich reaction.
Scheme 2: Retrosynthetic analysis of piperazirum.
Scheme 3: (a) iBuMgCl, Et2O, −78 °C; (b) KOH, EtOH/H2O, 100 °C; (c) (COCl)2.
Scheme 4: (a) Li(Et3BH), THF, rt then 14, CF3CO2H, −78 °C, dr 70:30; (b) (CF3CO)2O, Py, CH2Cl2, 0 °C to rt; (...
Scheme 5: (a) Li(Et3BH), CH2Cl2, rt then 19, CF3CO2H, −78 °C, dr >95:5; (b) Zn, 6 M HCl, EtOAc/EtOH, rt, sing...
Scheme 6: (a) (COCl)2, DMF, CH2Cl2, rt; (b) 21, Py, DMAP, CH2Cl2, rt; (c) EDC, HOBt, THF/CH2Cl2, rt; (d) H2 (...
Figure 1: X-ray crystal structure of 2·HCl.
C–C Bond formation catalyzed by natural gelatin and collagen proteins
- Dennis Kühbeck,
- Basab Bijayi Dhar,
- Eva-Maria Schön,
- Carlos Cativiela,
- Vicente Gotor-Fernández and
- David Díaz Díaz
Beilstein J. Org. Chem. 2013, 9, 1111–1118, doi:10.3762/bjoc.9.123
- implications from a metabolic perspective. Keywords: biocatalysis; carbon–carbon bond formation; gelatin; Henry reaction; protein; Introduction Gelatin is a mixture of hot-water-soluble proteins of high average molecular weights (50–100 kDa) derived primarily from collagen, which is the main naturally
- tin plate and shielded by Pt (40 mA during 30 s for FE-SEM; film thickness ≈5 nm). Typical procedure for gelatin-catalyzed Henry reaction Nitromethane (27 μL, 0.5 mmol) was added in one portion to a 4 mL screw cap vial containing 4-nitrobenzaldehyde (15.1 mg, 0.1 mmol), PSTA gelatin (2 mg) and DMSO
- . Typical procedure for gelatin hydrogel-catalyzed Henry reaction A mixture of PSTA (6 mg) in H2O (0.3 mL) was gently heated in a sealed screw cap vial (4 mL) until a homogeneous solution was obtained. This solution was stored overnight at rt to promote gel formation, which was confirmed by the complete
Graphical Abstract
Figure 1: Typical recycling experiments for the gelatin-catalyzed Henry reaction. Reaction conditions: 4-Nitr...
Figure 2: First-order kinetics plots for the model Henry reaction between 1a and 2a catalyzed by different sy...
Figure 3: Selected FESEM images of different catalysts used for comparative kinetics: (a) powdered BSA; (b) p...
