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Search for "selective reduction" in Full Text gives 48 result(s) in Beilstein Journal of Organic Chemistry.
Recent advancements in iodide/phosphine-mediated photoredox radical reactions
- Tinglan Liu,
- Yu Zhou,
- Junhong Tang and
- Chengming Wang
Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131
- has emerged as an attractive approach for nitroarene reduction [43][44]. In 2021, Huang and colleagues discovered a photoredox system that did not require any transition metal or other photosensitizers [45]. This system employed a combination of NaI and PPh3 to achieve highly selective reduction of
Graphical Abstract
Scheme 1: Photocatalytic decarboxylative transformations mediated by the NaI/PPh3 catalyst system.
Scheme 2: Proposed catalytic cycle of NaI/PPh3 photoredox catalysis.
Scheme 3: Decarboxylative alkenylation of redox-active esters by NaI/PPh3 catalysis.
Scheme 4: Decarboxylative alkenylation mediated by NaI/PPh3 catalysis.
Scheme 5: NaI-mediated photoinduced α-alkenylation of Katritzky salts 7.
Scheme 6: n-Bu4NI-mediated photoinduced decarboxylative olefination.
Scheme 7: Proposed mechanism of the n-Bu4NI-mediated photoinduced decarboxylative olefination.
Scheme 8: Photodecarboxylative alkylation of redox-active esters with diazirines.
Scheme 9: Photoinduced iodine-anion-catalyzed decarboxylative/deaminative C–H alkylation of enamides.
Scheme 10: Photocatalytic C–H alkylation of coumarins mediated by NaI/PPh3 catalysis.
Scheme 11: Photoredox alkylation of aldimines by NaI/PPh3 catalysis.
Scheme 12: Photoredox C–H alkylation employing ammonium iodide.
Scheme 13: NaI/PPh3/CuBr cooperative catalysis for photocatalytic C(sp3)–O/N cross-coupling reactions.
Scheme 14: Proposed mechanism of NaI/PPh3/CuBr cooperative catalysis for photocatalytic C(sp3)–O/N cross-coupl...
Scheme 15: Photocatalytic decarboxylative [3 + 2]/[4 + 2] annulation between enynals and γ,σ-unsaturated N-(ac...
Scheme 16: Proposed mechanism for the decarboxylative [3 + 2]/[4 + 2] annulation.
Scheme 17: Decarboxylative cascade annulation of alkenes/1,6-enynes with N-hydroxyphthalimide esters.
Scheme 18: Decarboxylative radical cascade cyclization of N-arylacrylamides.
Scheme 19: NaI/PPh3-driven photocatalytic decarboxylative radical cascade alkylarylation.
Scheme 20: Proposed mechanism of the NaI/PPh3-driven photocatalytic decarboxylative radical cascade cyclizatio...
Scheme 21: Visible-light-promoted decarboxylative cyclization of vinylcycloalkanes.
Scheme 22: NaI/PPh3-mediated photochemical reduction and amination of nitroarenes.
Scheme 23: PPh3-catalyzed alkylative iododecarboxylation with LiI.
Scheme 24: Visible-light-triggered iodination facilitated by N-heterocyclic carbenes.
Scheme 25: Visible-light-induced photolysis of phosphonium iodide salts for monofluoromethylation.
Photoredox catalysis harvesting multiple photon or electrochemical energies
- Mattia Lepori,
- Simon Schmid and
- Joshua P. Barham
Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81
Graphical Abstract
Figure 1: Oxidative and reductive activations of organic compounds harvesting photoredox catalysis.
Figure 2: General catalytic cycles of radical ion conPET (left) and radical ion e-PRC (right).
Figure 3: “Beginner’s guide”: comparison between advantages, capacities, and prospectives of conPET and PEC.
Figure 4: A) conPET reductive dehalogenation of aryl halides with PDI. B) Reductive C–H arylation with pyrrol...
Figure 5: A) Chromoselective mono- and disubstitution or polybrominated pyrimidines with pyrroles. B) Sequent...
Figure 6: A) Synthesis of pyrrolo[1,2-a]quinolines. B) Synthesis of ullazines.
Figure 7: A) Reductive phosphorylation of aryl halides via conPET. B) Selected examples from the substrate sc...
Figure 8: A) Reductive dehalogenation of aryl halides via conPET and selected examples from the substrate sco...
Figure 9: A) Reductive C–H arylation of aryl halides via conPET (top) and selected examples from the substrat...
Figure 10: A) Reductive hydrodehalogenation of aryl halides with Mes-Acr-BF4. B) Selected examples from the su...
Figure 11: A) Reductive hydrodechlorination of aryl chlorides with 4-DPAIPN. B) Proposed formation of CO2•−. C...
Figure 12: A) Reductive conPET borylation with 3CzEPAIPN (top) and selected examples from the substrate scope ...
Figure 13: Scale-up of conPET phosphorylation with 3CzEPAIPN.
Figure 14: A) Borylation of 1d. B) Characteristics and structure of PC1 with green and red parts showing the l...
Figure 15: A) Reductive C–H arylation scope with polysulfide conPET (top) and selected examples from the subst...
Figure 16: Scale-up of A) C–H arylation and B) dehaloborylation with polysulfide photocatalysis in continuous-...
Figure 17: A) Formation of [Ir1]0 and [Ir2]0 upon PET between [Ir1]+ and Et3N. B) Mechanism of multi-photon ta...
Figure 18: A) Reductive hydrodehalogenation of aryl halides via multi-photon tandem photocatalysis. B) Selecte...
Figure 19: A) Carbonylative amidation of aryl halides in continuous flow. B) Selected examples from the substr...
Figure 20: A) General scheme for reductive (RQ) and oxidative quenching (OQ) protocols using [FeIII(btz)3](PF6)...
Figure 21: A) Carbonylative amidation of alkyl iodides with [IrIII(ppy)2(dtbbpy)]PF6. B) Selected examples fro...
Figure 22: A) Carboxylative C–N bond cleavage in cyclic amines. B) Selected examples from the substrate scope....
Figure 23: A) Formal reduction of alkenes to alkanes via transfer hydrogenation. B) Selected examples from the...
Figure 24: A) Birch-type reduction of benzenes with PMP-BPI. B) Selected examples from the substrate scope (sc...
Figure 25: Proposed mechanism of the OH− mediated conPET Birch-type reduction of benzene via generation of sol...
Figure 26: Reductive detosylation of N-tosylated amides with Mes-Acr-BF4. B) Selected examples from the substr...
Figure 27: A) Reductive detosylation of N-tosyl amides by dual PRC. B) Selected examples from the substrate sc...
Figure 28: A) Mechanism of the dual PRC based on PET between [Cu(dap)2]+ and DCA. B) Mechanism of the dual PRC...
Figure 29: A) N–O bond cleavage in Weinreb amides with anthracene. B) N–O bond cleavage in Weinreb amides rely...
Figure 30: A) Pentafluorosulfanylation and fluoride elimination. B) Mechanism of the pentafluorosulfanylation ...
Figure 31: A) α-Alkoxypentafluorosulfanylation (top) and selected examples from the substrate scope (bottom). ...
Figure 32: A) Oxidative amination of arenes with azoles catalyzed by N-Ph PTZ. B) Selected examples from the s...
Figure 33: A) C(sp3)–H bond activation by HAT via chloride oxidation by *N-Ph PTZ•+. B) Proposed mechanism for...
Figure 34: A) Recycling e-PRC C–H azolation of electron-rich arenes with pyrazoles using Mes-Acr+ as a photoca...
Figure 35: A) Radical ion e-PRC direct oxidation of unactivated arenes using TAC+ as an electro-activated phot...
Figure 36: A) Radical ion e-PRC direct oxidation of unactivated arenes using TPA as an electro-activated photo...
Figure 37: Proposed mechanism (top) and mode of preassembly (bottom).
Figure 38: A) Possible preassemblies of reactive (left) vs unreactive (right) arenes. B) Calculated spin densi...
Figure 39: A) Recycling e-PRC C(sp2 )–H acetoxylation of arenes using DDQ as a photocatalyst. B) Proposed cata...
Figure 40: Gram scale hydroxylation of benzene in a recirculated flow setup.
Figure 41: A) Radical ion e-PRC vicinal diamination of alkylarenes using TAC+ as an electro-activated photocat...
Figure 42: A) Sequential oxygenation of multiple adjacent C–H bonds under radical ion e-PRC using TAC+ as an e...
Figure 43: A) Enantioselective recycling e-PRC cyanation of benzylic C–H bonds using ADQS as photocatalyst. B)...
Figure 44: Proposed tandem mechanism by Xu and co-workers.
Figure 45: A) Enantioselective recycling e-PRC decarboxylative cyanation using Cu(acac)2, Ce(OTf)3 and a box l...
Figure 46: A) Enantioselective recycling e-PRC benzylic cyanation using Cu(MeCN)4BF4, box ligand and anthraqui...
Figure 47: A) Radical ion e-PRC acetoxyhydroxylation of aryl olefins using TAC+ as an electro-activated photoc...
Figure 48: Selected examples from the substrate scope.
Figure 49: Photoelectrochemical acetoxyhydroxylation in a recirculated flow setup.
Figure 50: A) Radical ion e-PRC aminooxygenation of aryl olefins using TAC+ as an electro-activated photocatal...
Figure 51: A) Recycling e-PRC C–H alkylation of heteroarenes with organic trifluoroborates using Mes-Acr+ as p...
Figure 52: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using CeCl3·7H2O as catalyst. B) ...
Figure 53: A) Recycling e-PRC decarboxylative C–H alkylation of heteroarenes using Fe(NH4)2(SO4)2·6H2O as cata...
Figure 54: A) Recycling e-PRC C–H alkylation of heteroarenes with alkyl oxalates and 4CzIPN as photocatalyst. ...
Figure 55: A) Recycling e-PRC decarboxylative C–H carbamoylation of heteroarenes using 4CzIPN as photocatalyst...
Figure 56: A) Photoelectrochemical HAT-mediated hydrocarbon activation via the chlorine radical. B) Proposed m...
Figure 57: A) Selected examples from the substrate scope. B) Gram and decagram scale semi-continuous flow PEC ...
Figure 58: A) Photoelectrochemical HAT-mediated dehydrogenative coupling of benzothiazoles with aliphatic C–H ...
Figure 59: A) Photoelectrochemical HAT activation of ethers using electro-activated TAC+ as photocatalyst. B) ...
Figure 60: Selected examples from the substrate scope.
Figure 61: A) Photoelectrochemical HAT-mediated synthesis of alkylated benzimidazo-fused isoquinolinones using...
Figure 62: A) Decoupled photoelectrochemical cerium-catalyzed oxydichlorination of alkynes using CeCl3 as cata...
Figure 63: Proposed decoupled photoelectrochemical mechanism.
Figure 64: A) Decoupled photoelectrochemical ring-opening bromination of tertiary cycloalkanols using MgBr2 as...
Figure 65: A) Recycling e-PRC ring-opening functionalization of cycloalkanols using CeCl3 as catalyst. B) Prop...
Figure 66: Selected examples from the substrate scope of the PEC ring-opening functionalization.
Figure 67: A) Radical ion e-PRC reduction of chloro- and bromoarenes using DCA as catalyst and various accepto...
Figure 68: A) Screening of different phthalimide derivatives as catalyst for the e-PRC reduction of aryl halid...
Figure 69: Screening of different organic catalysts for the e-PRC reduction of trialkylanilium salts.
Figure 70: A) e-PRC reduction of phosphonated phenols and anilinium salts. B) Selected examples from the subst...
Figure 71: A) ConPET and e-PRC reduction of 4-bromobenzonitrile using a naphthalene diimide (NDI) precatalyst ...
Figure 72: A) Radical ion e-PRC reduction of phosphinated aliphatic alcohols with n-BuO-NpMI as catalyst. B) C...
Figure 73: Selected examples from the substrate scope.
Figure 74: A) Recycling e-PRC reductive dimerization of benzylic chlorides using a [Cu2] catalyst. B) Proposed...
Figure 75: A) Decoupled photoelectrochemical C–H alkylation of heteroarenes through deamination of Katritzky s...
Figure 76: Proposed mechanism by Chen and co-workers.
Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities
- Jorge de Lima Neto and
- Paulo Henrique Menezes
Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31
- . An o-phenolic coupling between two units of tyrosine furnishes the intermediate Int-1, which by deamination, selective reduction of one of the carboxylate groups, macrolactonization, and subsequent structural modifications would lead to the aforementioned combretastatins D (Scheme 1). The second
- carboxylic acid 20, which underwent protection with Troc-Cl and selective reduction in the presence of sodium borohydride to form the alcohol 21. After ester hydrolysis the desired seco-acid 22 was obtained in 82% yield. However, several attempts to achieve the macrolactonization of 22 using PPh3 and DEAD
Graphical Abstract
Figure 1: Structures of some members of the combretastatin D series, corniculatolides, and isocorniculatolide...
Scheme 1: Biosynthetic pathway proposed by Pettit and co-workers.
Scheme 2: Biosynthetic pathway towards corniculatolides or isocorniculatolides proposed by Ponnapalli and co-...
Scheme 3: Retrosynthetic approaches.
Scheme 4: Attempt of total synthesis of 2 by Boger and co-workers employing the Mitsunobu approach [27].
Scheme 5: Total synthesis of combretastatin D-2 (2) reported by Boger and co-workers employing an intramolecu...
Scheme 6: Formal synthesis of combretastatin D-2 (2) by Deshpande and co-workers using the Mitsunobu conditio...
Scheme 7: Total synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 8: Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36].
Scheme 9: Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41].
Scheme 10: Synthesis of fragment 57 by Couladouros and co-workers [43,45].
Scheme 11: Formal synthesis of compound 2 by Couladouros and co-workers [43,45].
Scheme 12: Synthesis of fragment 66 by Couladouros and co-workers [44,45].
Scheme 13: Synthesis of fragment 70 by Couladouros and co-workers [44,45].
Scheme 14: Synthesis of fragment 77 by Couladouros and co-workers [44,45].
Scheme 15: Synthesis of combretastatins 1 and 2 by Couladouros and co-workers [44,45].
Scheme 16: Formal synthesis of compound 2 by Gangakhedkar and co-workers [48].
Scheme 17: Synthesis of fragment 14 by Cousin and co-workers [50].
Scheme 18: Synthesis of fragment 91 by Cousin and co-workers [50].
Scheme 19: Formal synthesis of compound 2 by Cousin and co-workers [50].
Scheme 20: Synthesis of 2 diolide by Cousin and co-workers [50].
Scheme 21: Synthesis of combretastatin D-4 (4) by Nishiyama and co-workers [54].
Scheme 22: Synthesis of fragment 112 by Pettit and co-workers [55].
Scheme 23: Synthesis of fragment 114 by Pettit and co-workers [55].
Scheme 24: Attempt to the synthesis of compound 2 by Pettit and co-workers [55].
Scheme 25: Synthesis of combretastatin-D2 (2) starting from isovanilin (80) by Pettit and co-workers [55].
Scheme 26: Attempted synthesis of combretastatin-D2 (2) derivatives through an SNAr approach [55].
Scheme 27: Synthesis of combretastatin D-4 (4) by Pettit and co-workers [55].
Scheme 28: Synthesis of combretastatin D-2 (2) by Harras and co-workers [57].
Scheme 29: Synthesis of combretastatin D-4 (4) by Harras and co-workers [57].
Scheme 30: Formal synthesis of combretastatin D-1 (1) by Harras and co-workers [57].
Scheme 31: Synthesis of 11-O-methylcorniculatolide A (5) by Raut and co-workers [69].
Scheme 32: Synthesis of isocorniculatolide A (7) and O-methylated isocorniculatolide A 8 by Raut and co-worker...
Scheme 33: Synthesis of isocorniculatolide B (10) and hydroxyisocorniculatolide B 175 by Kim and co-workers [71].
Scheme 34: Synthesis of compound 9, 178, and 11 by Kim and co-workers [71].
Scheme 35: Synthesis of combretastatin D-2 prodrug salts [55].
Figure 2: ED50 values of the combretastatin D family against murine P388 lymphocytic leukemia cell line (appr...
Figure 3: IC50 of compounds against α-glucosidase [19].
Site-selective reactions mediated by molecular containers
- Rui Wang and
- Yang Yu
Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35
- Except for controlled cycloadditions, the site-selective reduction is also difficile to achieve. It mainly depends on the oxidative difference between the potential reactive sites and the careful picking of reductive reagents. Once the oxidative properties of these sites are similar to each other, it is
- mode, the molecular container selectively binds with and shields a certain part of the guest molecule and leaves the remaining part exposed to the reaction medium. This methodology was firstly applied to the site-selective reduction reaction mediated by a cyclodextrin host. In 1991, the Takahashi group
- could be regarded as a protective group by shielding the internal alkenyl site. In 2016, the Rebek group achieved the site-selective reduction of an α,ω-diazide compound by trimethylphosphine (PMe3) in aqueous solution with a cavitand host as the protecting group for one of the azide sites (Figure 5
Graphical Abstract
Figure 1: Site-selective Diels–Alder reaction of anthracene and phthalimide mediated by aqueous organopalladi...
Figure 2: Site-selective Diels–Alder and [2 + 2]-photoaddition reactions between naphthalene and phthalimide ...
Figure 3: Cage host A-mediated selective 1,4-radical addition of o-quinone 10.
Figure 4: Cyclodextrin-mediated site-selective reductions.
Figure 5: Selective reduction of an α,ω-diazide compound mediated by water-soluble cavitand D.
Figure 6: Selective radical reduction of α,ω-dihalides mediated by water-soluble cavitands E and F.
Figure 7: Site-selective hydrogenation of polyenols mediated by supramolecular encapsulated rhodium catalyst.
Figure 8: Site-selective oxidation of steroids using cyclodextrin as the anchoring template.
Figure 9: Site-selective oxidations of linear diterpenoids with the help of cage host A.
Figure 10: Site-selective monoepoxidation of α,ω-dienes mediated by the water-soluble cavitand host E.
Figure 11: Site-selective ring-opening reaction of epoxides mediated by cavitand I with an inwardly directed c...
Figure 12: Site-selective nucleophilic substitution reaction of allylic chlorides mediated by cage host J.
Figure 13: Site-selective monohydrolysis of α,ω-difunctional compounds using deep water-soluble cavitands.
Total synthesis of ent-pavettamine
- Memory Zimuwandeyi,
- Manuel A. Fernandes,
- Amanda L. Rousseau and
- Moira L. Bode
Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99
- yield. The first step involved esterification of malic acid using methanol, followed by selective reduction of the resulting dimethyl ester using borane dimethyl sulfide (BMS) yielding diol 5 (Scheme 2) [1][14][15]. The step achieved chemo-differentiation of the carboxyl groups present in 3 whilst
Graphical Abstract
Figure 1: Structure of pavettamine 1 and its enantiomer 2.
Scheme 1: Established route for the synthesis of intermediate 4 [1].
Scheme 2: Alternative route. Reaction conditions: a) TrCl, pyridine, rt, overnight, 100%; b) DMAP, imidazole,...
Figure 2: Crystal structure of compound 9.
Scheme 3: Sequence showing the source of compound 9.
Scheme 4: Stereoselective reduction of intermediate 8 as key step towards intermediate 4. Reaction conditions...
Figure 3: Single crystal X-ray structure of compound 4.
Scheme 5: Synthesis of the C5 fragments from intermediate 4. Reaction conditions: a) i) TFAA, collidine, 0 °C...
Scheme 6: Synthesis of ent-pavettamine as the TFA salt 28. Reaction conditions: a) IBX, DMSO, rt, overnight, ...
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.
All-carbon [3 + 2] cycloaddition in natural product synthesis
- Zhuo Wang and
- Junyang Liu
Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251
- ) via Tu’s protocol [64]. The synthesis of sinensilactam A (20) commenced with a three-step synthesis from ketoeseter 131 to give enone 132 [59] (Scheme 9C). Selective reduction of the ketone moiety of 132 was accomplished under Luche’s conditions [65] in the presence of calcium chloride [63] to produce
Graphical Abstract
Figure 1: Highly-substituted five-membered carbocycle in biologically significant natural products.
Figure 2: Natural product synthesis featuring the all-carbon [3 + 2] cycloaddition. (Quaternary carbon center...
Scheme 1: Representative natural product syntheses that feature the all-carbon [3 + 2] cyclization as the key...
Scheme 2: (A) An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition with allenyl diazo compound 38...
Scheme 3: (A) Palladium-catalyzed intermolecular carboxylative TMM cycloaddition [36]. (B) The proposed mechanism....
Scheme 4: Natural product syntheses that make use of palladium-catalyzed intermolecular [3 + 2] cycloaddition...
Scheme 5: (A) Phosphine-catalyzed [3 + 2] cycloaddition [17]. (B) The proposed mechanism.
Scheme 6: Lu’s [3 + 2] cycloaddition in natural product synthesis. (A) Synthesis of longeracinphyllin A (10) [41]...
Scheme 7: (A) Phosphine-catalyzed [3 + 2] annulation of unsymmetric isoindigo 100 with allene in the preparat...
Scheme 8: (A) Rhodium-catalyzed intracmolecular [3 + 2] cycloaddition [49]. (B) The proposed catalytic cycle of t...
Scheme 9: Total synthesis of natural products reported by Yang and co-workers applying rhodium-catalyzed intr...
Scheme 10: (A) Platinum(II)-catalyzed intermolecular [3 + 2] cycloaddition of propargyl ether 139 and n-butyl ...
Scheme 11: (A) Platinum-catalyzed intramolecular [3 + 2] cycloaddition of propargylic ketal derivative 142 to ...
Scheme 12: (A) Synthesis of phyllocladanol (21) features a Lewis acid-catalyzed formal intramolecular [3 + 2] ...
Scheme 13: The recent advances of [3 + 2] annulation in natural product synthesis. (A) The preparation of melo...
Recent developments in enantioselective photocatalysis
- Callum Prentice,
- James Morrisson,
- Andrew D. Smith and
- Eli Zysman-Colman
Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197
Graphical Abstract
Scheme 1: Amine/photoredox-catalysed α-alkylation of aldehydes with alkyl bromides bearing electron-withdrawi...
Scheme 2: Amine/HAT/photoredox-catalysed α-functionalisation of aldehydes using alkenes.
Scheme 3: Amine/cobalt/photoredox-catalysed α-functionalisation of ketones and THIQs.
Scheme 4: Amine/photoredox-catalysed α-functionalisation of aldehydes or ketones with imines. (a) Using keton...
Scheme 5: Bifunctional amine/photoredox-catalysed enantioselective α-functionalisation of aldehydes.
Scheme 6: Bifunctional amine/photoredox-catalysed α-functionalisation of aldehydes using amine catalysts via ...
Scheme 7: Amine/photoredox-catalysed RCA of iminium ion intermediates. (a) Synthesis of quaternary stereocent...
Scheme 8: Bifunctional amine/photoredox-catalysed RCA of enones in a radical chain reaction initiated by an i...
Scheme 9: Bifunctional amine/photoredox-catalysed RCA reactions of iminium ions with different radical precur...
Scheme 10: Bifunctional amine/photoredox-catalysed radical cascade reactions between enones and alkenes with a...
Scheme 11: Amine/photocatalysed photocycloadditions of iminium ion intermediates. (a) External photocatalyst u...
Scheme 12: Amine/photoredox-catalysed addition of acrolein (94) to iminium ions.
Scheme 13: Dual NHC/photoredox-catalysed acylation of THIQs.
Scheme 14: NHC/photocatalysed spirocyclisation via photoisomerisation of an extended Breslow intermediate.
Scheme 15: CPA/photoredox-catalysed aza-pinacol cyclisation.
Scheme 16: CPA/photoredox-catalysed Minisci-type reaction between azaarenes and α-amino radicals.
Scheme 17: CPA/photoredox-catalysed radical additions to azaarenes. (a) α-Amino radical or ketyl radical addit...
Scheme 18: CPA/photoredox-catalysed reduction of azaarene-derived substrates. (a) Reduction of ketones. (b) Ex...
Scheme 19: CPA/photoredox-catalysed radical coupling reactions of α-amino radicals with α-carbonyl radicals. (...
Scheme 20: CPA/photoredox-catalysed Povarov reaction.
Scheme 21: CPA/photoredox-catalysed reactions with imines. (a) Decarboxylative imine generation followed by Po...
Scheme 22: Bifunctional CPA/photocatalysed [2 + 2] photocycloadditions.
Scheme 23: PTC/photocatalysed oxygenation of 1-indanone-derived β-keto esters.
Scheme 24: PTC/photoredox-catalysed perfluoroalkylation of 1-indanone-derived β-keto esters via a radical chai...
Scheme 25: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolon...
Scheme 26: Bifunctional hydrogen bonding/photocatalysed intramolecular RCA cyclisation of a quinolone.
Scheme 27: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolon...
Scheme 28: Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloaddition reactions. (a) First use of...
Scheme 29: Bifunctional hydrogen bonding/photocatalysed deracemisation of allenes.
Scheme 30: Bifunctional hydrogen bonding/photocatalysed deracemisation reactions. (a) Deracemisation of sulfox...
Scheme 31: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloaddition of coumarins....
Scheme 32: Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloadditions of quinolones. (a) Intramo...
Scheme 33: Hydrogen bonding/photocatalysed formal arylation of benzofuranones.
Scheme 34: Hydrogen bonding/photoredox-catalysed dehalogenative protonation of α,α-chlorofluoro ketones.
Scheme 35: Hydrogen bonding/photoredox-catalysed reductions. (a) Reduction of 1,2-diketones. (b) Reduction of ...
Scheme 36: Hydrogen bonding/HAT/photocatalysed deracemisation of cyclic ureas.
Scheme 37: Hydrogen bonding/HAT/photoredox-catalysed synthesis of cyclic sulfonamides.
Scheme 38: Hydrogen bonding/photoredox-catalysed reaction between imines and indoles.
Scheme 39: Chiral cation/photoredox-catalysed radical coupling of two α-amino radicals.
Scheme 40: Chiral phosphate/photoredox-catalysed hydroetherfication of alkenols.
Scheme 41: Chiral phosphate/photoredox-catalysed synthesis of pyrroloindolines.
Scheme 42: Chiral anion/photoredox-catalysed radical cation Diels–Alder reaction.
Scheme 43: Lewis acid/photoredox-catalysed cycloadditions of carbonyls. (a) Formal [2 + 2] cycloaddition of en...
Scheme 44: Lewis acid/photoredox-catalysed RCA reaction using a scandium Lewis acid between α-amino radicals a...
Scheme 45: Lewis acid/photoredox-catalysed RCA reaction using a copper Lewis acid between α-amino radicals and...
Scheme 46: Lewis acid/photoredox-catalysed synthesis of 1,2-amino alcohols from aldehydes and nitrones using a...
Scheme 47: Lewis acid/photocatalysed [2 + 2] photocycloadditions of enones and alkenes.
Scheme 48: Meggers’s chiral-at-metal catalysts.
Scheme 49: Lewis acid/photoredox-catalysed α-functionalisation of ketones with alkyl bromides bearing electron...
Scheme 50: Bifunctional Lewis acid/photoredox-catalysed radical coupling reaction using α-chloroketones and α-...
Scheme 51: Lewis acid/photocatalysed RCA of enones. (a) Using aldehydes as acyl radical precursors. (b) Other ...
Scheme 52: Bifunctional Lewis acid/photocatalysis for a photocycloaddition of enones.
Scheme 53: Lewis acid/photoredox-catalysed RCA reactions of enones using DHPs as radical precursors.
Scheme 54: Lewis acid/photoredox-catalysed functionalisation of β-ketoesters. (a) Hydroxylation reaction catal...
Scheme 55: Bifunctional copper-photocatalysed alkylation of imines.
Scheme 56: Copper/photocatalysed alkylation of imines. (a) Bifunctional copper catalysis using α-silyl amines....
Scheme 57: Bifunctional Lewis acid/photocatalysed intramolecular [2 + 2] photocycloaddition.
Scheme 58: Bifunctional Lewis acid/photocatalysed [2 + 2] photocycloadditions (a) Intramolecular cycloaddition...
Scheme 59: Bifunctional Lewis acid/photocatalysed rearrangement of 2,4-dieneones.
Scheme 60: Lewis acid/photocatalysed [2 + 2] cycloadditions of cinnamate esters and styrenes.
Scheme 61: Nickel/photoredox-catalysed arylation of α-amino acids using aryl bromides.
Scheme 62: Nickel/photoredox catalysis. (a) Desymmetrisation of cyclic meso-anhydrides using benzyl trifluorob...
Scheme 63: Nickel/photoredox catalysis for the acyl-carbamoylation of alkenes with aldehydes using TBADT as a ...
Scheme 64: Bifunctional copper/photoredox-catalysed C–N coupling between α-chloro amides and carbazoles or ind...
Scheme 65: Bifunctional copper/photoredox-catalysed difunctionalisation of alkenes with alkynes and alkyl or a...
Scheme 66: Copper/photoredox-catalysed decarboxylative cyanation of benzyl phthalimide esters.
Scheme 67: Copper/photoredox-catalysed cyanation reactions using TMSCN. (a) Propargylic cyanation (b) Ring ope...
Scheme 68: Palladium/photoredox-catalysed allylic alkylation reactions. (a) Using alkyl DHPs as radical precur...
Scheme 69: Manganese/photoredox-catalysed epoxidation of terminal alkenes.
Scheme 70: Chromium/photoredox-catalysed allylation of aldehydes.
Scheme 71: Enzyme/photoredox-catalysed dehalogenation of halolactones.
Scheme 72: Enzyme/photoredox-catalysed dehalogenative cyclisation.
Scheme 73: Enzyme/photoredox-catalysed reduction of cyclic imines.
Scheme 74: Enzyme/photocatalysed enantioselective reduction of electron-deficient alkenes as mixtures of (E)/(Z...
Scheme 75: Enzyme/photoredox catalysis. (a) Deacetoxylation of cyclic ketones. (b) Reduction of heteroaromatic...
Scheme 76: Enzyme/photoredox-catalysed synthesis of indole-3-ones from 2-arylindoles.
Scheme 77: Enzyme/HAT/photoredox catalysis for the DKR of primary amines.
Scheme 78: Bifunctional enzyme/photoredox-catalysed benzylic C–H hydroxylation of trifluoromethylated arenes.
Syntheses of spliceostatins and thailanstatins: a review
- William A. Donaldson
Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166
- 22 to generate the secondary alcohol 23. The acylation of 23, followed by the treatment with Jones’ reagent effected the THP deprotection as well as an overoxidation to give 13. The syn-selective reduction of 13 was accomplished with a balloon worth of pressure of H2 in the presence of the Lindlar
Graphical Abstract
Figure 1: Structures of spliceostatins/thailanstatins.
Scheme 1: Synthetic routes to protected (2Z,4S)-4-hydroxy-2-butenoic acid fragments.
Scheme 2: Kitahara synthesis of the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran.
Scheme 3: Koide synthesis of (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran.
Scheme 4: Nicolaou synthesis of the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran.
Scheme 5: Jacobsen synthesis of the (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran.
Scheme 6: Unproductive attempt to generate the (all-cis)-tetrahydropyranone 50.
Scheme 7: Ghosh synthesis of the C-7–C-14 (all-cis)-tetrahydropyran segment.
Scheme 8: Ghosh’s alternative route to the (all-cis)-tetrahydropyranone 50.
Scheme 9: Alternative synthesis of the dihydro-3-pyrone 58.
Scheme 10: Kitahara’s 1st-generation synthesis of the C-1–C-6 fragment of FR901464 (1).
Scheme 11: Kitahara 1st-generation synthesis of the C-1–C-6 fragment of FR901464 (1).
Scheme 12: Nimura/Arisawa synthesis of the C-1-phenyl segment.
Scheme 13: Ghosh synthesis of the C-1–C-6 fragment of FR901464 (1) from (R)-glyceraldehyde acetonide.
Scheme 14: Jacobsen synthesis of the C-1–C-7 segment of FR901464 (1).
Scheme 15: Koide synthesis of the C-1–C-7 segment of FR901464 (1).
Scheme 16: Ghosh synthesis of the C-1–C-5 segment 102 of thailanstatin A (7).
Scheme 17: Nicolaou synthesis of the C-1–C-9 segments of spliceostatin D (9) and thailanstatins A (7) and B (5...
Scheme 18: Ghosh synthesis of the C-1–C-6 segment 115 of spliceostatin E (10).
Scheme 19: Fragment coupling via Wittig and modified Julia olefinations by Kitahara.
Scheme 20: Fragment coupling via cross-metathesis by Koide.
Scheme 21: The Ghosh synthesis of spliceostatin A (4), FR901464 (1), spliceostatin E (10), and thailanstatin m...
Scheme 22: Arisawa synthesis of a C-1-phenyl analog of FR901464 (1).
Scheme 23: Jacobsen fragment coupling by a Pd-catalyzed Negishi coupling.
Scheme 24: Nicolaou syntheses of thailanstatin A and B (7 and 5) and spliceostatin D (9) via a Pd-catalyzed Su...
Scheme 25: The Ghosh synthesis of spliceostatin G (11) via Suzuki–Miyaura coupling.
Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes
- Andreas H. Heindl and
- Hermann A. Wegner
Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4
- . The azobenzene building block 8, with an unsubstituted phenyl ring and two orthogonal nitrogen substituents in the 3- and 5-position (Scheme 3), was prepared. The synthesis commenced with the acetylation of 3,5-dinitroaniline (4) in 95% yield, followed by the selective reduction of one nitro group
Graphical Abstract
Figure 1: 1,3,5-Tris(arylazo)benzenes as individually switchable multistate photoswitches: previous [11,12] and pres...
Scheme 1: Synthetic strategy towards 1,3,5-tris(arylazo)benzenes 3 based on consecutive Baeyer–Mills reaction...
Scheme 2: Preparation of tris(arylazo)benzenes 3 by Pd-catalyzed cross-coupling reactions of N-Boc-arylhydraz...
Scheme 3: Synthesis of azobenzene building block 8.
Scheme 4: Synthesis of 1,3-bis(4-methoxyphenylazo)-5-phenylazobenzene (14).
Scheme 5: Synthesis of unsymmetrical tris(arylazo)benzenes 3a/3b using Pd-catalyzed coupling reactions and Cu...
Scheme 6: Coupling reactions of 15 with the corresponding arylhydrazides to access monocoupled (16a/16b) and ...
Figure 2: a) UV–vis spectra of tris(arylazo)benzenes 3a/3b in ethanol. b) Reversible photoisomerization of 3a...
A review of the total syntheses of triptolide
- Xiang Zhang,
- Zaozao Xiao and
- Hongtao Xu
Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194
- construction of the butenolide (D-ring) and iii) the installation of the three successive epoxides (C-ring). In future syntheses the following issues should be considered: i) avoiding the isomerization of the C-5 chiral center; ii) development of a new method for the β-selective reduction of the C-14 carbonyl
Graphical Abstract
Figure 1: Structures of triptolide (1), triptonide (2), tripdiolide (3), 16-hydroxytriptolide (4), triptrioli...
Figure 2: Syntheses of triptolide.
Scheme 1: Berchtold’s synthesis of triptolide.
Scheme 2: Li’s formal synthesis of triptolide.
Scheme 3: van Tamelen’s asymmetric synthesis of triptonide and triptolide.
Scheme 4: Van Tamelen’s (method II) formal synthesis of triptolide.
Scheme 5: Sherburn’s formal synthesis of triptolide.
Scheme 6: van Tamelen’s biogenetic type total synthesis of triptolide.
Scheme 7: Yang’s total synthesis of triptolide.
Scheme 8: Key intermediates or transformations of routes J–N.
N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds
- Iwona E. Głowacka,
- Aleksandra Trocha,
- Andrzej E. Wróblewski and
- Dorota G. Piotrowska
Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168
- aziridine esters 70 which were subjected to a selective reduction of the nitro group to afford the major pyrrolidine-2-one (2R,4'R,1''S)-71 after chromatographic purification [65]. The reduction of the amide bond gave (2R,3'R,1''S)-72 thus providing a cyclic part of (3S,3'R)-68. The transformation of the
Graphical Abstract
Figure 1: Examples of three-carbon chirons.
Figure 2: Structures of derivatives of N-(1-phenylethyl)aziridine-2-carboxylic acid 5–8.
Figure 3: Synthetic equivalency of aziridine aldehydes 6.
Scheme 1: Synthesis of N-(1-phenylethyl)aziridine-2-carboxylates 5. Reagents and conditions: a) TEA, toluene,...
Scheme 2: Absolute configuration at C2 in (2S,1'S)-5a. Reagents and conditions: a) 20% HClO4, 80 °C, 30 h the...
Scheme 3: Major synthetic strategies for a 2-ketoaziridine scaffold [R* = (R)- or (S)-1-phenylethyl; R′ = Alk...
Scheme 4: Synthesis of cyanide (2S,1'S)-13. Reagents and conditions: a) NH3, EtOH/H2O, rt, 72 h; b) Ph3P, CCl4...
Scheme 5: Synthesis of key intermediates (R)-16 and (R)-17 for (R,R)-formoterol (14) and (R)-tamsulosin (15)....
Scheme 6: Synthesis of mitotic kinesin inhibitors (2R/S,1'R)-23. Reagents and conditions: a) H2, Pd(OH)2, EtO...
Scheme 7: Synthesis of (R)-mexiletine ((R)-24). Reagents and conditions: a) TsCl, TEA, DMAP, CH2Cl2, rt, 1 h;...
Scheme 8: Synthesis of (−)-cathinone ((S)-27). Reagents and conditions: a) PhMgBr, ether, 0 °C; b) H2, 10% Pd...
Scheme 9: Synthesis of N-Boc-norpseudoephedrine ((1S,2S)-(+)-29) and N-Boc-norephedrine ((1R,2S)-29). Reagent...
Scheme 10: Synthesis of (−)-ephedrine ((1R,2S)-31). Reagents and conditions: a) TfOMe, MeCN then NaBH3CN, rt; ...
Scheme 11: Synthesis of xestoaminol C ((2S,3R)-35), 3-epi-xestoaminol C ((2S,3S)-35) and N-Boc-spisulosine ((2S...
Scheme 12: Synthesis of ʟ-tryptophanol ((S)-41). Reagents and conditions: a) CDI, MeCN, rt, 1 h then TMSI, MeC...
Scheme 13: Synthesis of ʟ-homophenylalaninol ((S)-42). Reagents and conditions: a) NaH, THF, 0 °C to −78 °C, 1...
Scheme 14: Synthesis of ᴅ-homo(4-octylphenyl)alaninol ((R)-47) and a sphingolipid analogue (R)-48. Reagents an...
Scheme 15: Synthesis of florfenicol ((1R,2S)-49). Reagents and conditions: a) (S)-1-phenylethylamine, TEA, MeO...
Scheme 16: Synthesis of natural tyroscherin ((2S,3R,6E,8R,10R)-55). Reagents and conditions: a) I(CH2)3OTIPS, t...
Scheme 17: Syntheses of (−)-hygrine (S)-61, (−)-hygroline (2S,2'S)-62 and (−)-pseudohygroline (2S,2'R)-62. Rea...
Scheme 18: Synthesis of pyrrolidine (3S,3'R)-68, a fragment of the fluoroquinolone antibiotic PF-00951966. Rea...
Scheme 19: Synthesis of sphingolipid analogues (R)-76. Reagents and conditions: a) BnBr, Mg, THF, reflux, 6 h;...
Scheme 20: Synthesis of ᴅ-threo-PDMP (1R,2R)-81. Reagents and conditions: a) TMSCl, NaI, MeCN, rt, 1 h 50 min,...
Scheme 21: Synthesis of the sphingolipid analogue SG-14 (2S,3S)-84. Reagents and conditions: a) LiAlH4, THF, 0...
Scheme 22: Synthesis of the sphingolipid analogue SG-12 (2S,3R)-88. Reagents and conditions: a) 1-(bromomethyl...
Scheme 23: Synthesis of sphingosine-1-phosphate analogues DS-SG-44 and DS-SG-45 (2S,3R)-89a and (2S,3R)-89a. R...
Scheme 24: Synthesis of N-Boc-safingol ((2S,3S)-95) and N-Boc-ᴅ-erythro-sphinganine ((2S,3R)-95). Reagents and...
Scheme 25: Synthesis of ceramide analogues (2S,3R)-96. Reagents and conditions: a) NaBH4, ZnCl2, MeOH, −78 °C,...
Scheme 26: Synthesis of orthogonally protected serinols, (S)-101 and (R)-102. Reagents and conditions: a) BnBr...
Scheme 27: Synthesis of N-acetyl-3-phenylserinol ((1R,2R)-105). Reagents and conditions: a) AcOH, CH2Cl2, refl...
Scheme 28: Synthesis of (S)-linezolid (S)-107. Reagents and conditions: a) LiAlH4, THF, 0 °C to reflux; b) Boc2...
Scheme 29: Synthesis of (2S,3S,4R)-2-aminooctadecane-1,3,4-triol (ᴅ-ribo-phytosphingosine) (2S,3S,4R)-110. Rea...
Scheme 30: Syntheses of ᴅ-phenylalanine (R)-116. Reagents and conditions: a) AcOH, CH2Cl2, reflux, 4 h; b) MsC...
Scheme 31: Synthesis of N-Boc-ᴅ-3,3-diphenylalanine ((R)-122). Reagents and conditions: a) PhMgBr, THF, −78 °C...
Scheme 32: Synthesis of ethyl N,N’-di-Boc-ʟ-2,3-diaminopropanoate ((S)-125). Reagents and conditions: a) NaN3,...
Scheme 33: Synthesis of the bicyclic amino acid (S)-(+)-127. Reagents and conditions: a) BF3·OEt2, THF, 60 °C,...
Scheme 34: Synthesis of lacosamide, (R)-2-acetamido-N-benzyl-3-methoxypropanamide (R)-130. Reagents and condit...
Scheme 35: Synthesis of N-Boc-norfuranomycin ((2S,2'R)-133). Reagents and conditions: a) H2C=CHCH2I, NaH, THF,...
Scheme 36: Synthesis of MeBmt (2S,3R,4R,6E)-139. Reagents and conditions: a) diisopropyl (S,S)-tartrate (E)-cr...
Scheme 37: Synthesis of (+)-polyoxamic acid (2S,3S,4S)-144. Reagents and conditions: a) AD-mix-α, MeSO2NH2, t-...
Scheme 38: Synthesis of the protected 3-hydroxy-ʟ-glutamic acid (2S,3R)-148. Reagents and conditions: a) LiHMD...
Scheme 39: Synthesis of (+)-isoserine (R)-152. Reagents and conditions: a) AcCl, MeCN, rt, 0.5 h then Na2CO3, ...
Scheme 40: Synthesis of (3R,4S)-N3-Boc-3,4-diaminopentanoic acid (3R,4S)-155. Reagents and conditions: a) Ph3P...
Scheme 41: Synthesis of methyl (2S,3S,4S)-4-(dimethylamino)-2,3-dihydroxy-5-methoxypentanoate (2S,3S,4S)-159. ...
Scheme 42: Syntheses of methyl (3S,4S) 4,5-di-N-Boc-amino-3-hydroxypentanoate ((3S,4S)-164), methyl (3S,4S)-4-N...
Scheme 43: Syntheses of (3R,5S)-5-(aminomethyl)-3-(4-methoxyphenyl)dihydrofuran-2(3H)-one ((3R,5S)-168). Reage...
Scheme 44: Syntheses of a series of imidazolin-2-one dipeptides 175–177 (for R' and R'' see text). Reagents an...
Scheme 45: Syntheses of (2S,3S)-N-Boc-3-hydroxy-2-hydroxymethylpyrrolidine ((2S,3S)-179). Reagents and conditi...
Scheme 46: Syntheses of enantiomers of 1,4-dideoxy-1,4-imino-ʟ- and -ᴅ-lyxitols (2S,3R,4S)-182 and (2R,3S,4R)-...
Scheme 47: Synthesis of 1,4-dideoxy-1,4-imino-ʟ-ribitol (2S,3S,4R)-182. Reagents and conditions: a) AcOH, CH2Cl...
Scheme 48: Syntheses of 1,4-dideoxy-1,4-imino-ᴅ-arabinitol (2R,3R,4R)-182 and 1,4-dideoxy-1,4-imino-ᴅ-xylitol ...
Scheme 49: Syntheses of natural 2,5-imino-2,5,6-trideoxy-ʟ-gulo-heptitol ((2S,3R,4R,5R)-184) and its C4 epimer...
Scheme 50: Syntheses of (−)-dihydropinidine ((2S,6R)-187a) (R = C3H7) and (2S,6R)-isosolenopsins (2S,6R)-187b ...
Scheme 51: Syntheses of (+)-deoxocassine ((2S,3S,6R)-190a, R = C12H25) and (+)-spectaline ((2S,3S,6R)-190b, R ...
Scheme 52: Synthesis of (−)-microgrewiapine A ((2S,3R,6S)-194a) and (+)-microcosamine A ((2S,3R,6S)-194b). Rea...
Scheme 53: Syntheses of ʟ-1-deoxynojirimycin ((2S,3S,4S,5R)-200), ʟ-1-deoxymannojirimycin ((2S,3S,4S,5S)-200) ...
Scheme 54: Syntheses of 1-deoxy-ᴅ-galacto-homonojirimycin (2R,3S,4R,5S)-211. Reagents and conditions: a) MeONH...
Scheme 55: Syntheses of 7a-epi-hyacinthacine A1 (1S,2R,3R,7aS)-220. Reagents and conditions: a) TfOTBDMS, 2,6-...
Scheme 56: Syntheses of 8-deoxyhyacinthacine A1 ((1S,2R,3R,7aR)-221). Reagents and conditions: a) H2, Pd/C, PT...
Scheme 57: Syntheses of (+)-lentiginosine ((1S,2S,8aS)-227). Reagents and conditions: a) (EtO)2P(O)CH2COOEt, L...
Scheme 58: Syntheses of 8-epi-swainsonine (1S,2R,8S,8aR)-231. Reagents and conditions: a) Ph3P=CHCOOMe, MeOH, ...
Scheme 59: Synthesis of a protected vinylpiperidine (2S,3R)-237, a key intermediate in the synthesis of (−)-sw...
Scheme 60: Synthesis of a modified carbapenem 245. Reagents and conditions: a) AcOEt, LiHMDS, THF, −78 °C, 1.5...
Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes
- Guillaume Ernouf,
- Jean-Louis Brayer,
- Christophe Meyer and
- Janine Cossy
Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29
- )-1f. Selective reduction of phosphine oxide (E)-3f. Attempted thermal [2,3]-sigmatropic rearrangement of phosphinite 6a. Computed activation barriers and free enthalpies. [2,3]-Sigmatropic rearrangement of phosphinites 6a–j. Proposed mechanism for the Lewis base-catalyzed rearrangement of phosphinites
Graphical Abstract
Scheme 1: Representative strategies for the formation of alkylidenecyclopropanes from cyclopropenes and scope...
Scheme 2: [2,3]-Sigmatropic rearrangement of phosphinites 2a–h.
Scheme 3: [2,3]-Sigmatropic rearrangement of a phosphinite derived from enantioenriched cyclopropenylcarbinol...
Scheme 4: Selective reduction of phosphine oxide (E)-3f.
Scheme 5: Attempted thermal [2,3]-sigmatropic rearrangement of phosphinite 6a.
Scheme 6: Computed activation barriers and free enthalpies.
Scheme 7: [2,3]-Sigmatropic rearrangement of phosphinites 6a–j.
Scheme 8: Proposed mechanism for the Lewis base-catalyzed rearrangement of phosphinites 6.
Scheme 9: [3,3]-Sigmatropic rearrangement of tertiary cyclopropenylcarbinyl acetates 10a–c.
Scheme 10: [3,3]-Sigmatropic rearrangement of secondary cyclopropenylcarbinyl esters 10d–h.
Scheme 11: [3,3]-Sigmatropic rearrangement of trichoroacetimidates 12a–i.
Scheme 12: Reaction of trichloroacetamide 13f with pyrrolidine.
Scheme 13: Catalytic hydrogenation of (arylmethylene)cyclopropropane 13f.
Scheme 14: Instability of trichloroacetimidates 21a–c derived from cyclopropenylcarbinols 20a–c.
Scheme 15: [3,3]-Sigmatropic rearrangement of cyanate 27 generated from cyclopropenylcarbinyl carbamate 26.
Scheme 16: Synthesis of alkylidene(aminocyclopropane) derivatives 30–37 from carbamate 26.
Scheme 17: Scope of the dehydration–[3,3]-sigmatropic rearrangement sequence of cyclopropenylcarbinyl carbamat...
Scheme 18: Formation of trifluoroacetamide 50 from carbamate 49.
Scheme 19: Formation of alkylidene[(N-trifluoroacetylamino)cyclopropanes] 51–54.
Scheme 20: Diastereoselective hydrogenation of alkylidenecyclopropane 51.
Scheme 21: Ireland–Claisen rearrangement of cyclopropenylcarbinyl glycolates 56a–l.
Scheme 22: Synthesis and Ireland–Claisen rearrangement of glycolate 61 possessing gem-diester substitution at ...
Scheme 23: Synthesis of alkylidene(gem-difluorocyclopropanes) 66a–h, and 66k–n from propargyl glycolates 64a–n....
Scheme 24: Ireland–Claisen rearrangement of N,N-diBoc glycinates 67a and 67b.
Scheme 25: Diastereoselective hydrogenation of alkylidenecyclopropanes 58a and 74.
Scheme 26: Synthesis of functionalized gem-difluorocyclopropanes 76 and 77 from alkylidenecyclopropane 66a.
Scheme 27: Access to oxa- and azabicyclic compounds 78–80.
Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety
- Alex Frichert,
- Peter G. Jones and
- Thomas Lindel
Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222
- conversion to the diastereomer by oxidation and reduction. Conformational analysis of some of the resulting diols obtained under McMurry conditions was complicated by the presence of several conformers of similar energy. The pinacol coupling appears to start at the ketone, as indicated by the selective
- reduction of non-cyclizing cyclohexane systems that were synthesized from limonene oxide. The title compounds and their synthetic precursors are prone to aromatization on contact with air oxygen. Attempted synthesis of cyclohexene-containing eunicellane bicycles by elimination of water from tertiary alkynyl
Graphical Abstract
Figure 1: Bicyclic eunicellane-type diterpenes.
Figure 2: Synthetic eunicellane-type compounds with benzene partial structure.
Scheme 1: Access to ketoester 14 that did not cyclize to the ethyl vinyl ether under McMurry conditions.
Scheme 2: Synthesis of the 1,3-cyclohexadiene-containing eunicellane-type [8.4.0]bicycle 18 by McMurry coupli...
Figure 3: Preferred conformations of diastereomeric diols 18 and 19 including decisive NOESY correlations.
Scheme 3: Assembly of the envisaged cyclization precursor 27.
Scheme 4: Structure analysis of diastereomeric cyanohydrins 29 and 30.
Scheme 5: Formation of allenes 32 and 34 from sterically crowded propargylic alcohol 31.
Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I
- Pamarthi Gangadhar,
- Sayini Ramakrishna,
- Ponneri Venkateswarlu and
- Pabbaraja Srihari
Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206
- -selective reduction [25] of alkyne 20 was easily achieved with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) as a hydride-transfer reagent to furnish the corresponding (E)-allylic alcohol 23. A Swern oxidation of 23 provided the corresponding aldehyde which was subjected to an addition reaction with
Graphical Abstract
Figure 1: Proposed structures of a selection of diacetylenic polyol natural products.
Scheme 1: Retrosynthesis of strongylodiols H and I.
Scheme 2: Synthesis of alkyne 19 and iodo intermediate 21. Reagents and conditions: (a) n-BuLi, THF, −78 °C t...
Scheme 3: Stereoselective synthesis of (R)-25. Reagents and conditions: (a) CuCl, NH2OH·HCl, 30% n-BuNH2, Et2...
Figure 2: Absolute configuration analysis of alcohol 25. ∆δ = δS − δR for the (R)- and (S)-MTPA ester of alco...
Scheme 4: Synthesis of strongylodiol H (9). Reagents and conditions: (a) TBDPSCl, imidazole, CH2Cl2, 0 °C to ...
Figure 3: Previously proposed and revised structure of strongylodiol H (9).
Scheme 5: Synthesis of compound 25a. Reagents and conditions: (a) (R)-CBS catalyst, BH3·DMS, −50 °C, 16 h, 86...
Scheme 6: Synthesis of strongylodiol I (10a). Reagents and conditions: (a) (i) TBDPSCl, imidazole, CH2Cl2, 0 ...
Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions
- Nicole C. Neyt and
- Darren L. Riley
Beilstein J. Org. Chem. 2018, 14, 1529–1536, doi:10.3762/bjoc.14.129
- the selective reduction of aldehydes in the presence of ketones and has been demonstrated as a continuous process. Keywords: aldehyde reduction; flow chemistry; selective reduction; sodium dithionite; Introduction Flow chemistry and continuous processing has been acknowledged by the American
- sodium dithionite under basic conditions and the expansion of the approach to allow the selective reduction of aldehydes in the presence of ketones. Results and Discussion Batch-based reduction of aldehydes and ketones The reduction of simple aldehydes and ketones (Table 1, Scheme 1) were envisaged and
- cases the yields were considered to be too low to be of use even though in certain examples (Table 1, entries 1.15 and 1.17) the productivity was arguably moderately better (2.4 and 2.0 times, respectively) than that of the analogous batch processes. Selective reduction of aldehydes in the presence of
Graphical Abstract
Scheme 1: Sodium dithionite-mediated reductions under basic conditions.
Figure 1: Uniqsis FlowSyn Stainless Steel Flow reactor.
Figure 2: Flow reactor configuration for the reduction of aldehydes and ketones.
Figure 3: NMR spectra showing the optimisation of the dithionite reduction for the reduction of benzaldehyde.
Figure 4: Selective reduction of an aldehyde in the presence of a ketone.
Figure 5: Flow reactor set-up for the continuous reduction of aldehydes.
A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols
- Anna Czarnecka,
- Emilia Kowalska,
- Agnieszka Bodzioch,
- Joanna Skalik,
- Marek Koprowski,
- Krzysztof Owsianik and
- Piotr Bałczewski
Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105
- % yields and is recommended for the substrates containing sulfur atoms, for which transition metal-induced reactions fail. Keywords: diarylmethanes; diarylmethanols; 1,3-dithiane; selective reduction; sodium cyanoborohydride; zinc iodide; Introduction In last decades, diarylmethanes, such as I–IV and
- , and their reduction to the corresponding ortho-1,3-dithianylaryl(aryl)methanes. Attempts of the OH removal in ortho-1,3-dithianyl- 6b and ortho-1,3-dioxanylaryl(aryl)methanols 9 using the Pd-catalyzed hydrogenolysis reaction. A selective reduction of ortho-1,3-dithianylaryl(aryl)methanols to ortho-1,3
Graphical Abstract
Figure 1: Structures of biologically active diarylmethanes and commercially available pharmaceuticals based o...
Scheme 1: Various synthetic approaches to diarylmethanols (literature review and this work).
Scheme 2: A general strategy for the synthesis of ortho-1,3-dithianylaryl(aryl)methanols 5 and 6, and their r...
Scheme 3: Attempts of the OH removal in ortho-1,3-dithianyl- 6b and ortho-1,3-dioxanylaryl(aryl)methanols 9 u...
The chemistry and biology of mycolactones
- Matthias Gehringer and
- Karl-Heinz Altmann
Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159
- literature-known aldehyde (R)-17, which defined the configuration of the C19 stereocenter (mycolactone numbering, see Figure 1). Aldehyde (R)-17 can be easily prepared from commercially available methyl (R)-3-hydroxybutyrate ((R)-47, see Scheme 4) in two steps, namely TBS protection followed by selective
- reduction with DIBAL-H [125]. Aldehyde (R)-17 was submitted to an asymmetric Brown crotylation reaction [126][127] to establish the C16 and C17 stereocenters. Of note, all four possible C16,C17-diastereomers of 18 were prepared (not shown) by using different combinations of (E)- or (Z)-butene and either
Graphical Abstract
Figure 1: Initial proposal for the core macrolactone structure (left) and the established complete structure ...
Figure 2: Mycolactone congeners and their origins.
Figure 3: Misassigned mycolactone E structure according to Small et al. [50] (11) and the correct structure (6) f...
Figure 4: Schematic illustration of Kishi’s improved mycolactone TLC detection method exploiting derivatizati...
Figure 5: Fluorescent probes derived from natural mycolactone A/B (1a,b) or its synthetic 8-desmethyl analogs...
Figure 6: Tool compounds used by Pluschke and co-workers for elucidating the molecular targets of mycolactone...
Figure 7: Synthetic strategies towards the extended mycolactone core. A) General strategies. B) Kishi’s appro...
Scheme 1: Kishi’s 1st generation approach towards the extended core structure of mycolactones. Reagents and c...
Scheme 2: Kishi’s 2nd generation approach towards the extended core structure of mycolactones. Reagents and c...
Scheme 3: Kishi’s 3rd generation approach towards the extended core structure of mycolactones. Reagents and c...
Scheme 4: Negishi’s synthesis of the extended core structure of mycolactones. Reagents and conditions: a) (i) ...
Scheme 5: Burkart’s (incomplete) 1st generation approach towards the extended core structure of mycolactones....
Scheme 6: Burkart’s (incomplete) 1st, 2nd and 3rd generation approach towards the extended mycolactone core s...
Scheme 7: Altmann’s synthesis of alkyl iodide 91. Reagents and conditions: a) (i) PMB-trichloroacetimidate, T...
Scheme 8: Final steps of Altmann’s synthesis of the extended core structure of mycolactones. Reagents and con...
Scheme 9: Basic principles of the Aggarwal lithiation–borylation homologation process [185,186].
Scheme 10: Aggarwal’s synthesis of the C1–C11 fragment of the mycolactone core. Reagents and conditions: a) Cl...
Scheme 11: Aggarwal’s synthesis of the linear C1–C20 fragment of the mycolactone core. Reagents and conditions...
Figure 8: Synthetic strategies towards the mycolactone A/B lower side chain.
Scheme 12: Gurjar and Cherian’s synthesis of the C1’–C8’ fragment of the mycolactone A/B pentaenoate side chai...
Scheme 13: Gurjar and Cherian’s synthesis of the benzyl-protected mycolactone A/B pentaenoate side chain. Reag...
Scheme 14: Kishi’s synthesis of model compounds for elucidating the stereochemistry of the C7’–C16’ fragment o...
Scheme 15: Kishi’s synthesis of the mycolactone A/B pentaenoate side chain. (a) (i) NaH, (EtO)2P(O)CH2CO2Et, T...
Scheme 16: Feringa and Minnaard's incomplete synthesis of mycolactone A/B pentaenoate side chain. Reagents and...
Scheme 17: Altmann’s approach towards the mycolactone A/B pentaenoate side chain. Reagents and conditions: a) ...
Scheme 18: Negishi’s access to the C1’–C7’ fragment of mycolactone A. Reagents and conditions: a) (i) n-BuLi, ...
Scheme 19: Negishi’s approach to the C1’–C7’ fragment of mycolactone B. Reagents and conditions: a) (i) DIBAL-...
Scheme 20: Negishi’s synthesis of the C8’–C16’ fragment of mycolactone A/B. Reagents and conditions: a) 142, BF...
Scheme 21: Negishi’s assembly of the mycolactone A and B pentaenoate side chains. Reagents and conditions: a) ...
Scheme 22: Blanchard’s approach to the mycolactone A/B pentaenoate side chain. a) (i) Ph3P=C(Me)COOEt, CH2Cl2,...
Scheme 23: Kishi’s approach to the mycolactone C pentaenoate side chain exemplified for the 13’R,15’S-isomer 1...
Scheme 24: Altmann’s (unpublished) synthesis of the mycolactone C pentaenoate side chain. Reagents and conditi...
Scheme 25: Blanchard’s synthesis of the mycolactone C pentaenoate side chain. Reagents and conditions: a) (i) ...
Scheme 26: Kishi’s synthesis of the tetraenoate side chain of mycolactone F exemplified by enantiomer 165. Rea...
Scheme 27: Kishi’s synthesis of the mycolactone E tetraenoate side chain. Reagents and conditions: a) (i) CH2=...
Scheme 28: Wang and Dai’s synthesis of the mycolactone E tetraenoate side chain. Reagents and conditions: a) (...
Scheme 29: Kishi’s synthesis of the dithiane-protected tetraenoate side chain of the minor oxo-metabolite of m...
Scheme 30: Kishi’s synthesis of the mycolactone S1 and S2 pentaenoate side chains. Reagents and conditions: a)...
Scheme 31: Kishi’s 1st generation and Altmann’s total synthesis of mycolactone A/B (1a,b) and Negishi’s select...
Scheme 32: Kishi’s 2nd generation total synthesis of mycolactone A/B (1a,b). Reagents and conditions: a) 2,4,6...
Scheme 33: Blanchard’s synthesis of the 8-desmethylmycolactone core. Reagents and conditions: a) (i) TsCl, TEA...
Scheme 34: Altmann’s (partially unpublished) synthesis of the C20-hydroxylated mycolactone core. Reagents and ...
Scheme 35: Altmann’s and Blanchard’s approaches towards the 11-isopropyl-8-desmethylmycolactone core. Reagents...
Scheme 36: Blanchard’s synthesis of the saturated variant of the C11-isopropyl-8-desmethylmycolactone core. Re...
Scheme 37: Structure elucidation of photo-mycolactones generated from tetraenoate 224.
Scheme 38: Kishi’s synthesis of the linear precursor of the photo-mycolactone B1 lower side chain. Reagents an...
Scheme 39: Kishi’s synthesis of the photo-mycolactone B1 lower side chain. Reagents and conditions: a) LiTMP, ...
Scheme 40: Kishi’s synthesis of a stabilized lower mycolactone side chain. Reagents and conditions: a) (i) TBD...
Scheme 41: Blanchard’s variation of the C12’,C13’,C15’ stereocluster. Reagents and conditions: a) (i) DIBAL-H,...
Scheme 42: Blanchard’s synthesis of aromatic mycolactone polyenoate side chain analogs. Reagents and condition...
Scheme 43: Small’s partial synthesis of a BODIPY-labeled mycolactone derivative and Demangel’s partial synthes...
Scheme 44: Blanchard’s synthesis of the BODIPY-labeled 8-desmethylmycolactones. Reagents and conditions: a) (i...
Scheme 45: Altmann’s synthesis of biotinylated mycolactones. Reagents and conditions: a) (i) CDI, THF, rt, 2 d...
Figure 9: Kishi’s elongated n-butyl carbamoyl mycolactone A/B analog.
Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis
- Flavio Fanelli,
- Giovanna Parisi,
- Leonardo Degennaro and
- Renzo Luisi
Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51
- to handle hazardous components such as hydrazine and molecular oxygen, which represent alternative reagents for selective reduction of C=C double bonds. In fact, combination of hydrazine hydrate (N2H4·H2O) and O2 provide diimide (HN=NH) as reducing agent. Nevertheless, this strategy is rarely used in
- is compatible with sensitive functional groups such as silyl ether, halogenes, and benzyl groups. A very nice application of this approach was the highly selective reduction of artemisinic acid to dihydroartemisinic acid, which are of interest in the synthesis of the antimalarial drug artemisinin
Graphical Abstract
Figure 1: Microreactor technologies and flow chemistry for a sustainable chemistry.
Scheme 1: A flow microreactor system for the generation and trapping of highly unstable carbamoyllithium spec...
Scheme 2: Flow synthesis of functionalized α-ketoamides.
Scheme 3: Reactions of benzyllithiums.
Scheme 4: Trapping of benzyllithiums bearing carbonyl groups enabled by a flow microreactor. (Adapted with pe...
Scheme 5: External trapping of chloromethyllithium in a flow microreactor system.
Scheme 6: Scope for the direct tert-butoxycarbonylation using a flow microreactor system.
Scheme 7: Control of anionic Fries rearrangement reactions by using submillisecond residence time. (Adapted w...
Figure 2: Chip microreactor (CMR) fabricated with six layers of polyimide films. (Reproduced with permission ...
Scheme 8: Flow microreactor system for lithiation, borylation, Suzuki–Miyaura coupling and selected examples ...
Scheme 9: Experimental setup for the flow synthesis of 2-fluorobi(hetero)aryls by directed lithiation, zincat...
Scheme 10: Experimental setup for the coupling of fluoro-substituted pyridines. (Adapted with permission from [53]...
Scheme 11: Continuous flow process setup for the preparation of 11 (Reproduced with permission from [54], copyrigh...
Scheme 12: Continuous-flow photocatalytic oxidation of thiols to disulfides.
Scheme 13: Trifluoromethylation by continuous-flow photoredox catalysis.
Scheme 14: Flow photochemical synthesis of 6(5H)-phenanthridiones from 2-chlorobenzamides.
Scheme 15: Synthesis of biaryls 14a–g under photochemical flow conditions.
Scheme 16: Flow oxidation of hydrazones to diazo compounds.
Scheme 17: Synthetic use of flow-generated diazo compounds.
Scheme 18: Ley’s flow approach for the generation of diazo compounds.
Scheme 19: Iterative strategy for the sequential coupling of diazo compounds.
Scheme 20: Integrated synthesis of Bakuchiol precursor via flow-generated diazo compounds.
Scheme 21: Kappe’s continuous-flow reduction of olefines with diimide.
Scheme 22: Multi-injection setup for the reduction of artemisinic acid.
Scheme 23: Flow reactor system for multistep synthesis of (S)-rolipram. Pumps are labelled a, b, c, d and e; L...
Figure 3: Reconfigurable modules and flowcharts for API synthesis. (Reproduced with permission from [85], copyrig...
Figure 4: Reconfigurable system for continuous production and formulation of APIs. (Reproduced with permissio...
Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs
- Arne Klinkebiel,
- Ole Beyer,
- Barbara Malawko and
- Ulrich Lüning
Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219
- monofunctionalized 1,3,5-triazines 16b and 16c carrying methyl ester groups at the end of each „arm“ (Figure 7). The yields of 90% (16b) and 73% (16c) correspond to 97% and 90% yield per coupling step, respectively. By selective reduction, the nitro-substituted triester 16b could be transferred into its amino
Graphical Abstract
Figure 1: Steric repulsion between ortho-hydrogen atoms in benzene-1,3,5-tribenzoic acid (BTB) leads to a non...
Figure 2: Mono-substituted TATB linkers 1b–d were successfully employed in the isoreticular syntheses of PCN-...
Figure 3: Retrosynthetic analysis for extended TATBs 2: triple Suzuki coupling between tribromotriazines 3 an...
Figure 4: Synthesis of unsymmetrically substituted 2,4,6-tris(bromoaryl)-1,3,5-triazines 3 from one equivalen...
Figure 5: Synthesis of 4-bromo-3-nitrobenzoyl chloride (5b). Conditions: a) HNO3/H2SO4, 3 h 0 °C, 2 h, room t...
Figure 6: Syntheses of 4-bromo-3-methoxybenzoyl chloride (5c). Conditions: a) Br2, EtOH/HOAc, 30 min, room te...
Figure 7: Triple Suzuki–Miyaura coupling between tribromotriazines 3 and boronic acid 15 and subsequent hydro...
Figure 8: Triple Suzuki coupling between tribromotriazines 3 and boronate 18. Conditions: a) 19a: Pd(PPh3)4, K...
Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives
- Yan Li,
- Xue Zhou,
- Guangfan Zheng and
- Qian Zhang
Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293
- investigate the synthetic value of our new aminooxygenation method. Then, the selective reduction of 3g was conducted (Scheme 3). The cleavage of the N–O bond in 3g readily occurred with Mo(CO)6/Et3N at 80 °C to give alcohol 4 [36] in 67% yield. Treatment of 3g with NH2NH2·H2O under mild conditions (25 °C) in
- (1.2 mmol, 4.0 equiv), 2 (0.3 mmol, 1.0 equiv), CuCl2 (10 mol %), DCM (2.0 mL), N2, 70 °C, 10.0 h. Isolated yields. Copper-catalyzed radical aminooxygenation reaction of styrenes. The plausible mechanism. Selective reduction of the aminooxygenation product. The optimization of reaction conditionsa
Graphical Abstract
Figure 1: Bioactive compounds containing 1,2-aminoalcohol motif.
Scheme 1: Copper-catalyzed radical aminooxygenation reaction of styrenes.
Figure 2: The copper-catalyzed three-component aminooxygenation of styrenes with NFSI and NHPI derivatives. R...
Scheme 2: The plausible mechanism.
Scheme 3: Selective reduction of the aminooxygenation product.
Catalytic asymmetric formal synthesis of beraprost
- Yusuke Kobayashi,
- Ryuta Kuramoto and
- Yoshiji Takemoto
Beilstein J. Org. Chem. 2015, 11, 2654–2660, doi:10.3762/bjoc.11.285
- , the proposed strategy offers an efficient construction of all stereocenters of tricyclic core 2, based on the initially established chiral stereocenter, as the configuration at the C1 and C2 positions of 2 would presumably be controlled by face-selective reduction of ketone 3. The Michael precursor 7
Graphical Abstract
Figure 1: Structure of PGI2 and beraprost (1).
Scheme 1: Retrosynthetic analysis of beraprost (1).
Scheme 2: Preparation of Michael precursors 7 and 8.
Scheme 3: First attempt at the synthesis of 2 from 6.
Scheme 4: Achievement of a formal synthesis of 2.
Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms
- Tatjana Huber,
- Lara Weisheit and
- Thomas Magauer
Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273
- oxolane bridge between C1 and C7. Hajos–Parrish diketone (107) [39] served as the starting material for the preparation of key intermediate 112. Selective reduction of the ketone and silylation of the resulting alcohol furnished enone 108. α-Carboxylation of the enone with magnesium methyl carbonate and a
Graphical Abstract
Figure 1: a) Structure of xenicin (1) and b) numbering of the xenicane skeleton according to Schmitz and van ...
Figure 2: Overview of selected Xenia diterpenoids according to the four subclasses [2-20]. The nine-membered carboc...
Figure 3: Representative members of the caryophyllenes, azamilides and Dictyota diterpenes.
Scheme 1: Proposed biosynthesis of Xenia diterpenoids (OPP = pyrophosphate, GGPP = geranylgeranyl pyrophospha...
Scheme 2: Direct synthesis of the nine-membered carbocycle as proposed by Schmitz and van der Helm (E = elect...
Scheme 3: The construction of E- or Z-cyclononenes.
Scheme 4: Total synthesis of racemic β-caryophyllene (22) by Corey.
Scheme 5: Total synthesis of racemic β-caryophyllene (22) by Oishi.
Scheme 6: Total synthesis of coraxeniolide A (10) by Leumann.
Scheme 7: Total synthesis of antheliolide A (18) by Corey.
Scheme 8: a) Synthesis of enantiomer 80, b) total syntheses of coraxeniolide A (10) and c) β-caryophyllene (22...
Scheme 9: Total synthesis of blumiolide C (11) by Altmann.
Scheme 10: Synthesis of a xeniolide F precursor by Hiersemann.
Scheme 11: Synthesis of the xenibellol (15) and the umbellacetal (114) core by Danishefsky.
Scheme 12: Proposed biosynthesis of plumisclerin A (118).
Scheme 13: Synthesis of the tricyclic core structure of plumisclerin A by Yao.
Scheme 14: Total synthesis of 4-hydroxydictyolactone (137) by Williams.
Scheme 15: Photoisomerization of 4-hydroxydictyolactone (137) to 4-hydroxycrenulide (138).
Scheme 16: The total synthesis of (+)-acetoxycrenulide (151) by Paquette.
Total synthesis of panicein A2
- Lili Yeung,
- Lisa I. Pilkington,
- Melissa M. Cadelis,
- Brent R. Copp and
- David Barker
Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215
- . to provide ketone 12 in 66% yield [8]. The selective reduction of the olefin in α,β-unsaturated ketone 12 was then attempted using the Raney nickel catalyst under hydrogen as previously reported [8]; unfortunately no product 13 was formed. Following this, a range of conditions were employed to reduce
Graphical Abstract
Figure 1: Members of the panicein family of aromatic sesquiterpenoids.
Figure 2: Proposed biogenesis of panicein A2 (5).
Figure 3: Retrosynthetic analysis of panicein A2 (5).
Scheme 1: Synthesis of ketone 13.
Scheme 2: Synthesis of propargyl ether 8 through formation of trifluoroacetate intermediate 17.
Scheme 3: Synthesis of propargyl ether 8 through carbonate 18.
Scheme 4: Synthesis of panicein A2 (5).
Synthesis of a tricyclic lactam via Beckmann rearrangement and ring-rearrangement metathesis as key steps
- Sambasivarao Kotha,
- Ongolu Ravikumar and
- Jadab Majhi
Beilstein J. Org. Chem. 2015, 11, 1503–1508, doi:10.3762/bjoc.11.163
- ]. Results and Discussion To begin with, the oxidation of dicyclopentadiene (5) in the presence of SeO2 gave 1α-dicyclopentadienol (6), which on treatment with pyridinium chlorochromate (PCC) [31] delivered the known tricyclic enone 4. Selective reduction of enone 4 with Zn in AcOH/EtOH under reflux
Graphical Abstract
Figure 1: Retrosynthetic analysis of tricyclic amide 1.
Scheme 1: Synthesis of tricyclic ketone 4.
Scheme 2: Beckmann rearrangement of oximes 8a and 8b.
Scheme 3: Beckmann rearrangement reaction in a single step.
Scheme 4: Synthesis of ring-rearrangement precursors.
Scheme 5: Synthesis of Beckmann rearrangement precursors.
Scheme 6: Beckmann rearrangement of oxime isomers 11a and 11b.
Figure 2: Molecular crystal structure of compound 11b.
Scheme 7: Synthesis of aza tricyclic compound 1 by RRM.
