Search for "methylation" in Full Text gives 270 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66
Graphical Abstract
Figure 1: Structure of lumateperone.
Scheme 1: First synthetic route leading to lumateperone (1).
Scheme 2: Alternate synthesis of lumateperone.
Scheme 3: Alternate synthetic approaches leading to racemic lumateperone ((±)-1)).
Scheme 4: Planned new synthesis of key intermediate (±)-9a.
Scheme 5: New synthesis of key intermediate (±)-9a.
Scheme 6: Trifluoroacetylation of tetrahydroquinoxaline (37).
Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61
Graphical Abstract
Scheme 1: Photochemical transformations of 3-hydroxypyran-4-one derivatives.
Scheme 2: Synthesis and study of the photochemical behavior of compound 16.
Scheme 3: Photoreaction of compound 12a.
Figure 1: 1H NMR monitoring of the photoreaction of compound 12a under UV irradiation (365 nm) in DMSO-d6 sol...
Scheme 4: Proposed mechanism for the photoreaction of compound 11a.
Scheme 5: Synthesis of compounds 15a–l. Reaction conditions: 1) 12a–l (0.5 mmol), AcOH (25 mL), UV irradiatio...
Figure 2: The X-ray crystal structure of compound 15a.
Scheme 6: Synthesis of compounds 15m–o. Reaction conditions: 1) 12m–o (0.5 mmol), AcOH (25 mL), UV irradiatio...
Figure 3: The X-ray crystal structure of compound 15m.
Scheme 7: Synthesis of compound 18.
Figure 4: The X-ray crystal structure of compound 18.
Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53
Graphical Abstract
Figure 1: Molecular structures of (R)-BINOL (left) and (S)-BINOL (right).
Figure 2: Synthesis of Sauvage´s [2]catenanes (S,S)-5 and (S,S)-6 containing two BINOL units by the passive m...
Figure 3: Synthesis of Saito´s [2]rotaxane (R)-10 from a BINOL-based macrocycle by the active metal template ...
Figure 4: Synthesis of Stoddart´s [2]rotaxane (rac)-14 by an ammonium crown ether template.
Figure 5: Synthesis of Stoddart´s BINOL-containing [2]catenanes 18/20/22/24 by π–π recognition.
Figure 6: Synthesis of Takata´s rotaxanes featuring chiral centers on the axle: a) rotaxane (R,R,R/S)-27 obta...
Figure 7: Takata´s chiral polyacetylenes 32/33 featuring BINOL-based [2]rotaxane side chains.
Figure 8: Synthesis of Takata´s chiral thiazolium [2]rotaxanes (R)-35a/b and (R)-38.
Figure 9: Results for the asymmetric benzoin condensation of benzaldehyde (39) with catalysts (R)-35a/b and (R...
Figure 10: Synthesis of Takata´s pyridine-based [2]rotaxane (R)-42.
Figure 11: The asymmetric desymmetrization reaction of meso-1,2-diols with rotaxane (R)-42.
Figure 12: Synthesis of Niemeyer´s axially chiral [2]catenane (S,S)-47.
Figure 13: Results for the enantioselective transfer hydrogenation of 2-phenylquinoline with catalysts (S,S)-47...
Figure 14: Synthesis of Niemeyer´s chiral [2]rotaxanes (S)-56/57.
Figure 15: Results for the enantioselective Michael addition with different rotaxane catalysts (S)-56a/56b/57a/...
Figure 16: Synthesis of Beer´s [2]rotaxanes 64a/b for anion recognition.
Figure 17: Association constants of different anions (used as the Bu4N+ salts) to the [2]rotaxanes (S)-64a/b a...
Figure 18: Synthesis of Beer´s [3]rotaxane (S)-68.
Figure 19: Association constants of different anions (used as the Bu4N+-salts) to the [2]rotaxane (S)-68 and a...
Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43
Graphical Abstract
Figure 1: Natural bioactive naphthoquinones.
Figure 2: Chemical structures of vitamins K.
Figure 3: Redox cycle of menadione.
Scheme 1: Selected approaches for menadione synthesis using silver(I) as a catalyst.
Scheme 2: Methylation approaches for the preparation of menadione from 1,4-naphthoquinone using tert-butyl hy...
Scheme 3: Methylation approach of 1,4-naphthoquinone using i) rhodium complexes/methylboronic acid and ii) bi...
Scheme 4: Synthesis of menadione (10) from itaconic acid.
Scheme 5: Menadione synthesis via Diels–Alder reaction.
Scheme 6: Synthesis of menadione (10) using p-cresol as a synthetic precursor.
Scheme 7: Synthesis of menadione (10) via demethoxycarbonylating annulation of methyl methacrylate.
Scheme 8: Furan 34 used as a diene in a Diels–Alder reaction for the synthesis of menadione (10).
Scheme 9: o-Toluidine as a dienophile in a Diels–Alder reaction for the synthesis of menadione (10).
Scheme 10: Representation of electrochemical synthesis of menadione.
Figure 4: Reaction sites and reaction types of menadione as substrate.
Scheme 11: DBU-catalyzed epoxidation of menadione (10).
Scheme 12: Phase-transfer catalysis for the epoxidation of menadione.
Scheme 13: Menadione epoxidation using a hydroperoxide derived from (+)-norcamphor.
Scheme 14: Enantioselective Diels–Alder reaction for the synthesis of asymmetric quinone 50 catalyzed by a chi...
Scheme 15: Optimized reaction conditions for the synthesis of anthra[9,1-bc]pyranone.
Scheme 16: Synthesis of anthra[9,1-bc]furanone, anthra[9,1-bc]pyridine, and anthra[9,1-bc]pyrrole derivatives.
Scheme 17: Synthesis of derivatives employing protected trienes.
Scheme 18: Synthesis of cyclobutene derivatives of menadione.
Scheme 19: Menadione reduction reactions using sodium hydrosulfite.
Scheme 20: Green methodology for menadiol synthesis and pegylation.
Scheme 21: Menadione reduction by 5,6-O-isopropylidene-ʟ-ascorbic acid under UV light irradiation.
Scheme 22: Selected approaches of menadione hydroacetylation to diacetylated menadiol.
Scheme 23: Thiele–Winter reaction catalyzed by Bi(OTf)3.
Scheme 24: Carbonyl condensation of menadione using resorcinol and a hydrazone derivative.
Scheme 25: Condensation reaction of menadione with thiosemicarbazide.
Scheme 26: Condensation reaction of menadione with acylhydrazides.
Scheme 27: Menadione derivatives functionalized with organochalcogens.
Scheme 28: Synthesis of selenium-menadione conjugates derived from chloromethylated menadione 84.
Scheme 29: Menadione alkylation by the Kochi–Anderson method.
Scheme 30: Menadione alkylation by diacids.
Scheme 31: Menadione alkylation by heterocycles-substituted carboxylic acids.
Scheme 32: Menadione alkylation by bromoalkyl-substituted carboxylic acids.
Scheme 33: Menadione alkylation by complex carboxylic acids.
Scheme 34: Kochi–Anderson method variations for the menadione alkylation via oxidative decarboxylation of carb...
Scheme 35: Copper-catalyzed menadione alkylation via free radicals.
Scheme 36: Nickel-catalyzed menadione cyanoalkylation.
Scheme 37: Iron-catalyzed alkylation of menadione.
Scheme 38: Selected approaches to menadione alkylation.
Scheme 39: Menadione acylation by photo-Friedel–Crafts acylation reported by Waske and co-workers.
Scheme 40: Menadione acylation by Westwood procedure.
Scheme 41: Synthesis of 3-benzoylmenadione via metal-free TBAI/TBHP system.
Scheme 42: Michael-type addition of amines to menadione reported by Kallmayer.
Scheme 43: Synthesis of amino-menadione derivatives using polyalkylamines.
Scheme 44: Selected examples for the synthesis of different amino-substituted menadione derivatives.
Scheme 45: Selected examples of Michael-type addition of complex amines to menadione (10).
Scheme 46: Addition of different natural α-amino acids to menadione.
Scheme 47: Michael-type addition of amines to menadione using silica-supported perchloric acid.
Scheme 48: Indolylnaphthoquinone or indolylnaphthalene-1,4-diol synthesis reported by Yadav et al.
Scheme 49: Indolylnaphthoquinone synthesis reported by Tanoue and co-workers.
Scheme 50: Indolylnaphthoquinone synthesis from menadione by Escobeto-González and co-workers.
Scheme 51: Synthesis of menadione analogues functionalized with thiols.
Scheme 52: Synthesis of menadione-derived symmetrical derivatives through reaction with dithiols.
Scheme 53: Mercaptoalkyl acids as nucleophiles in Michael-type addition reaction to menadione.
Scheme 54: Reactions of menadione (10) with cysteine derivatives for the synthesis of quinoproteins.
Scheme 55: Synthesis of menadione-glutathione conjugate 152 by Michael-type addition.
Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40
Graphical Abstract
Figure 1: Chemical structures of amamistatins (1–5) and a putative biosynthetic shunt product (6) isolated in...
Figure 2: 1H,1H COSY and selected 1H,13C HMBC correlations in compounds 1 and 6.
Figure 3: MS–MS fragmentation of amamistatins (1–5).
Figure 4: Proposed biosynthesis of amamistatins isolated in this study.
Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3
Graphical Abstract
Figure 1: Selected examples of natural products and drugs possessing the indane scaffold.
Scheme 1: Known strategies and conceptual advance of this contribution.
Figure 2: Selected examples of bioactive spirobarbiturates.
Figure 3: The screened organocatalysts.
Scheme 2: Substrate scope of 2-isothiocyanato-1-indanones. The reactions were carried out with 1 (0.12 mmol), ...
Scheme 3: Substrate scope of barbiturate-based olefins. The reactions were carried out with 1a (0.12 mmol), 2...
Figure 4: X-ray crystal structure of 3ae (displacement ellipsoids are drawn at the 50% probability level).
Scheme 4: Gram-scale synthesis of 3ah.
Scheme 5: Further transformation of 3ah.
Scheme 6: One-pot three-component reaction.
Scheme 7: Proposed reaction mechanism.
Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206
Graphical Abstract
Figure 1: Some antitumor agents containing the 4-anilinoquinazoline moiety.
Scheme 1: Examples of N-arylation reactions using 4-chloroquinazolines as substrates.
Scheme 2: Synthesis of verubulin analog.
Scheme 3: Synthesis of 4-chloro-6-halo-2-phenylquinazolines 8a and 8b. Conditions: a) NBS, CH3CN, 30 min, 25 ...
Scheme 4: N-Arylation reactions using ortho-, meta-, and para-substituted primary anilines of type 14 followe...
Scheme 5: N-Arylation reactions using 4-chloroquinazoline (16) and 4-chloro-2-methylquinazoline (17) to achie...
Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172
Graphical Abstract
Figure 1: Generalized α-ketol or α-iminol rearrangement.
Figure 2: Nickel(II)-catalyzed enantioselective rearrangement of ketol 3 to form the ring-expanded and chiral...
Figure 3: Enantioselective ring expansion of β-hydroxy-α-dicarbonyl 6 catalyzed by a chiral copper-bisoxazoli...
Figure 4: Enantioselective rearrangement of ketols 9 and 12 and hydroxyaldimine 14 catalyzed by Al(III) or Sc...
Figure 5: Asymmetric rearrangement of α,α-dialkyl-α-siloxyaldehydes 16 to α-siloxyketones 17 catalyzed by chi...
Figure 6: BF3-promoted diastereospecific rearrangement of α-ketol 21 to difluoroalkoxyborane 22.
Figure 7: In the presence of a gold catalyst and water in 1,4-dioxane, 1-alkynylbutanol derivatives undergo t...
Figure 8: The diastereospecific α-ketol rearrangement of 32 to 33, part of the total synthesis of periconiano...
Figure 9: Two α-ketol rearrangements, one catalyzed by silica gel on 38 and the other by NaOMe on both 38 and ...
Figure 10: α-Ketol rearrangement of triumphalone (41) to isotriumphalone (42) via ring contraction.
Figure 11: Tandem reaction of strophasterol A synthetic intermediate 43 to 44 through a vinylogous α-ketol rea...
Figure 12: Tandem reaction consisting of a Diels–Alder cycloaddition followed by an α-ketol rearrangement, par...
Figure 13: Single-pot reaction consisting of Claisen and α-ketol rearrangements, part of the total synthesis o...
Figure 14: Enzyme-catalyzed α-ketol rearrangements. a) Ketol-acid reductoisomerase (KAR) catalyzes the rearran...
Figure 15: The conversion of asperfloroid (73) to asperflotone (72), featuring the ring-expanding α-ketol rear...
Figure 16: Hypothetical interconversion of natural products prekinamycin (76) and isoprekinamycin (77) and che...
Figure 17: Proposed biosynthetic pathway converting acylphloroglucinol (87) to isolated elodeoidins A–H 92–96....
Figure 18: α-Iminol rearrangements catalyzed by VANOL Zr (99). The rearrangement can be conducted with preform...
Figure 19: α-Iminol rearrangements catalyzed by silica gel and montmorillonite K 10. a) For 102a (102 with R =...
Figure 20: Synthesis of tryptamines 110 via a ring-contracting α‑iminol rearrangement. A mechanism for the fin...
Figure 21: Tandem synthesis of functionalized α-amino cyclopentanones 119 from heteroarenes 115 and cyclobutan...
Figure 22: Four eburnane-type alkaloid natural products 122–125 were synthesized from common intermediate 127,...
Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147
Graphical Abstract
Scheme 1: Chemical structures of queuine (Q base) and the hypermodified nucleoside queuosine (Q), the natural...
Scheme 2: Synthesis of compound 1 (m6preQ0) by cyclocondensation using a 4-methoxypyrimidine derivative resul...
Scheme 3: Synthesis of compound 3 following known procedures [31-33].
Scheme 4: The five-step synthesis of m6preQ1 2 from compound 3 required derivatization to make the intermedia...
Scheme 5: The synthesis of e6preQ1 (2a) and bn6preQ1 (2b) was performed in analogy to the route outlined in Scheme 4 ...
Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143
Graphical Abstract
Scheme 1: Nickel-catalyzed cross-coupling versus C‒H activation.
Figure 1: Oxidative and reductive quenching cycles of a photocatalyst. [PC] = photocatalyst, A = acceptor, D ...
Scheme 2: Photoredox nickel-catalyzed C(sp3)–H arylation of dimethylaniline (1a).
Scheme 3: Photoredox nickel-catalyzed arylation of α-amino, α-oxy and benzylic C(sp3)‒H bonds with aryl bromi...
Figure 2: Proposed catalytic cycle for the photoredox-mediated HAT and nickel catalysis enabled C(sp3)‒H aryl...
Scheme 4: Photoredox arylation of α-amino C(sp3)‒H bonds with aryl iodides.
Figure 3: Proposed mechanism for photoredox nickel-catalyzed α-amino C‒H arylation with aryl iodides.
Scheme 5: Nickel-catalyzed α-oxy C(sp3)−H arylation of cyclic and acyclic ethers.
Figure 4: Proposed catalytic cycle for the C(sp3)−H arylation of cyclic and acyclic ethers.
Scheme 6: Photochemical nickel-catalyzed C–H arylation of ethers.
Figure 5: Proposed catalytic cycle for the nickel-catalyzed arylation of ethers with aryl bromides.
Scheme 7: Nickel-catalyzed α-amino C(sp3)‒H arylation with aryl tosylates.
Scheme 8: Arylation of α-amino C(sp3)‒H bonds by in situ generated aryl tosylates from phenols.
Scheme 9: Formylation of aryl chlorides through redox-neutral 2-functionalization of 1,3-dioxolane (13).
Scheme 10: Photochemical C(sp3)–H arylation via a dual polyoxometalate HAT and nickel catalytic manifold.
Figure 6: Proposed mechanism for C(sp3)–H arylation through dual polyoxometalate HAT and nickel catalytic man...
Scheme 11: Photochemical nickel-catalyzed α-hydroxy C‒H arylation.
Scheme 12: Photochemical synthesis of fluoxetine (21).
Scheme 13: Photochemical nickel-catalyzed allylic C(sp3)‒H arylation with aryl bromides.
Figure 7: Proposed mechanism for the photochemical nickel-catalyzed allylic C(sp3)‒H arylation with aryl brom...
Scheme 14: Photochemical C(sp3)‒H arylation by the synergy of ketone HAT catalysis and nickel catalysis.
Figure 8: Proposed mechanism for photochemical C(sp3)‒H arylation by the synergy of ketone HAT catalysis and ...
Scheme 15: Benzophenone- and nickel-catalyzed photoredox benzylic C–H arylation.
Scheme 16: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)–H arylation.
Scheme 17: Photoredox and nickel-catalyzed enantioselective benzylic C–H arylation.
Figure 9: Proposed mechanism for the photoredox and nickel-catalyzed enantioselective benzylic C–H arylation.
Scheme 18: Photoredox nickel-catalyzed α-(sp3)‒H arylation of secondary benzamides with aryl bromides.
Scheme 19: Enantioselective sp3 α-arylation of benzamides.
Scheme 20: Nickel-catalyzed decarboxylative vinylation/C‒H arylation of cyclic oxalates.
Figure 10: Proposed mechanism for the nickel-catalyzed decarboxylative vinylation/C‒H arylation of cyclic oxal...
Scheme 21: C(sp3)−H arylation of bioactive molecules using mpg-CN photocatalysis and nickel catalysis.
Figure 11: Proposed mechanism for the mpg-CN/nickel photocatalytic C(sp3)–H arylation.
Scheme 22: Nickel-catalyzed synthesis of 1,1-diarylalkanes from alkyl bromides and aryl bromides.
Figure 12: Proposed mechanism for photoredox nickel-catalyzed C(sp3)–H alkylation via polarity-matched HAT.
Scheme 23: Photoredox nickel-catalyzed C(sp3)‒H alkylation via polarity-matched HAT.
Scheme 24: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)‒H alkylation of ethers.
Scheme 25: Benzaldehyde- and nickel-catalyzed photoredox C(sp3)‒H alkylation of amides and thioethers.
Scheme 26: Photoredox and nickel-catalyzed C(sp3)‒H alkylation of benzamides with alkyl bromides.
Scheme 27: CzIPN and nickel-catalyzed C(sp3)‒H alkylation of ethers with alkyl bromides.
Figure 13: Proposed mechanism for the CzIPN and nickel-catalyzed C(sp3)‒H alkylation of ethers.
Scheme 28: Nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides and acid chlorides using trimethy...
Figure 14: Proposed catalytic cycle for the nickel/photoredox-catalyzed methylation of (hetero)aryl chlorides ...
Scheme 29: Photochemical nickel-catalyzed C(sp3)–H methylations.
Scheme 30: Photoredox nickel catalysis-enabled alkylation of unactivated C(sp3)–H bonds with alkyl bromides.
Scheme 31: Photochemical C(sp3)–H alkenylation with alkenyl tosylates.
Scheme 32: Photoredox nickel-catalyzed hydroalkylation of internal alkynes.
Figure 15: Proposed mechanism for the photoredox nickel-catalyzed hydroalkylation of internal alkynes.
Scheme 33: Photoredox nickel-catalyzed hydroalkylation of activated alkynes with C(sp3)−H bonds.
Scheme 34: Allylation of unactivated C(sp3)−H bonds with allylic chlorides.
Scheme 35: Photochemical nickel-catalyzed α-amino C(sp3)–H allylation of secondary amides with trifluoromethyl...
Scheme 36: Photoredox δ C(sp3)‒H allylation of secondary amides with trifluoromethylated alkenes.
Scheme 37: Photoredox nickel-catalyzed acylation of α-amino C(sp3)‒H bonds of N-arylamines.
Figure 16: Proposed mechanism for the photoredox nickel-catalyzed acylation of α-amino C(sp3)–H bonds of N-ary...
Scheme 38: Photocatalytic α‑acylation of ethers with acid chlorides.
Figure 17: Proposed mechanism for the photocatalytic α‑acylation of ethers with acid chlorides.
Scheme 39: Photoredox and nickel-catalyzed C(sp3)‒H esterification with chloroformates.
Scheme 40: Photoredox nickel-catalyzed dehydrogenative coupling of benzylic and aldehydic C–H bonds.
Figure 18: Proposed reaction pathway for the photoredox nickel-catalyzed dehydrogenative coupling of benzylic ...
Scheme 41: Photoredox nickel-catalyzed enantioselective acylation of α-amino C(sp3)–H bonds with carboxylic ac...
Scheme 42: Nickel-catalyzed C(sp3)‒H acylation with N-acylsuccinimides.
Figure 19: Proposed mechanism for the nickel-catalyzed C(sp3)–H acylation with N-acylsuccinimides.
Scheme 43: Nickel-catalyzed benzylic C–H functionalization with acid chlorides 45.
Scheme 44: Photoredox nickel-catalyzed benzylic C–H acylation with N-acylsuccinimides 84.
Scheme 45: Photoredox nickel-catalyzed acylation of indoles 86 with α-oxoacids 87.
Scheme 46: Nickel-catalyzed aldehyde C–H functionalization.
Figure 20: Proposed catalytic cycle for the photoredox nickel-catalyzed aldehyde C–H functionalization.
Scheme 47: Photoredox carboxylation of methylbenzenes with CO2.
Figure 21: Proposed mechanism for the photoredox carboxylation of methylbenzenes with CO2.
Scheme 48: Decatungstate photo-HAT and nickel catalysis enabled alkene difunctionalization.
Figure 22: Proposed catalytic cycle for the decatungstate photo-HAT and nickel catalysis enabled alkene difunc...
Scheme 49: Diaryl ketone HAT catalysis and nickel catalysis enabled dicarbofunctionalization of alkenes.
Figure 23: Proposed catalytic mechanism for the diaryl ketone HAT catalysis and nickel catalysis enabled dicar...
Scheme 50: Overview of photoredox nickel-catalyzed C–H functionalizations.
Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129
Graphical Abstract
Figure 1: Overview of the methods available for the synthesis of polysaccharides. For each method, advantages...
Figure 2: Overview of the classes of polysaccharides discussed in this review. Each section deals with polysa...
Scheme 1: Enzymatic and chemical polymerization approaches provide cellulose oligomers with a non-uniform dis...
Scheme 2: AGA of a collection of cellulose analogues obtained using BBs 6–9. Specifically placed modification...
Figure 3: Chemical structure of the different branches G, X, L, F commonly found in XGs. Names are given foll...
Scheme 3: AGA of XG analogues with defined side chains. The AGA cycle includes coupling (TMSOTf), Fmoc deprot...
Figure 4: Synthetic strategies and issues associated to the formation of the β(1–3) linkage.
Scheme 4: Convergent synthesis of β(1–3)-glucans using a regioselective glycosylation strategy.
Scheme 5: DMF-mediated 1,2-cis glycosylation. A) General mechanism and B) examples of α-glucans prepared usin...
Scheme 6: Synergistic glycosylation strategy employing a nucleophilic modulation strategy (TMSI and Ph3PO) in...
Scheme 7: Different approaches to produce xylans. A) Polymerization techniques including ROP, and B) enzymati...
Scheme 8: A) Synthesis of arabinofuranosyl-decorated xylan oligosaccharides using AGA. Representative compoun...
Scheme 9: Chemoenzymatic synthesis of COS utilizing a lysozyme-catalyzed transglycosylation reaction followed...
Scheme 10: Synthesis of COS using an orthogonal glycosylation strategy based on the use of two different LGs.
Scheme 11: Orthogonal N-PGs permitted the synthesis of COS with different PA.
Scheme 12: AGA of well-defined COS with different PA using two orthogonally protected BBs. The AGA cycle inclu...
Scheme 13: A) AGA of β(1–6)-N-acetylglucosamine hexasaccharide and dodecasaccharide. AGA includes cycles of co...
Figure 5: ‘Double-faced’ chemistry exemplified for ᴅ-Man and ʟ-Rha. Constructing β-Man linkages is considerab...
Figure 6: Implementation of a capping step after each glycosylation cycle for the AGA of a 50mer oligomannosi...
Scheme 14: AGA enabled the synthesis of a linear α(1–6)-mannoside 100mer 93 within 188 h and with an average s...
Scheme 15: The 151mer branched polymannoside was synthesized by a [30 + 30 + 30 + 30 + 31] fragment coupling. ...
Figure 7: PG stereocontrol strategy to obtain β-mannosides. A) The mechanism of the β-mannosylation reaction ...
Scheme 16: A) Mechanism of 1,2-cis stereoselective glycosylation using ManA donors. Once the ManA donor is act...
Figure 8: A) The preferred 4H3 conformation of the gulosyl oxocarbenium ion favors the attack of the alcohol ...
Scheme 17: AGA of type I rhamnans up to 16mer using disaccharide BB 115 and CNPiv PG. The AGA cycle includes c...
Figure 9: Key BBs for the synthesis of the O-antigen of Bacteroides vulgatus up to a 128mer (A) and the CPS o...
Figure 10: Examples of type I and type II galactans synthesized to date.
Figure 11: A) The DTBS PG stabilizes the 3H4 conformation of the Gal oxocarbenium ion favoring the attack of t...
Figure 12: Homogalacturonan oligosaccharides synthesized to date. Access to different patterns of methyl-ester...
Figure 13: GlfT2 from Mycobacterium tuberculosis catalyzes the sequential addition of UPD-Galf donor to a grow...
Figure 14: The poor reactivity of acceptor 137 hindered a stepwise synthesis of the linear galactan backbone a...
Scheme 18: AGA of a linear β(1–5) and β(1–6)-linked galactan 20mer. The AGA cycle includes coupling (NIS/TfOH)...
Figure 15: The 92mer arabinogalactan was synthesized using a [31 + 31 + 30] fragment coupling between a 31mer ...
Scheme 19: Synthesis of the branched arabinofuranose fragment using a six component one-pot synthesis. i) TTBP...
Figure 16: A) Chemical structure and SNFG of the representative disaccharide units forming the GAG backbones, ...
Figure 17: Synthetic challenges associated to the H/HS synthesis.
Scheme 20: Degradation of natural heparin and heparosan generated valuable disaccharides 150 and 151 that can ...
Scheme 21: A) The one-step conversion of cyanohydrin 156 to ʟ-iduronamide 157 represent the key step for the s...
Scheme 22: A) Chemoenzymatic synthesis of heparin structures, using different types of UDP activated natural a...
Scheme 23: Synthesis of the longest synthetic CS chain 181 (24mer) using donor 179 and acceptor 180 in an iter...
Scheme 24: AGA of a collection of HA with different lengths. The AGA cycle includes coupling (TfOH) and Lev de...
Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126
Graphical Abstract
Scheme 1: Schematic overview of transition metals studied in C–H activation processes.
Scheme 2: (A) Known biological activities related to benzimidazole-based compounds; (B and C) an example of a...
Scheme 3: (A) Known biological activities related to quinoline-based compounds; (B and C) an example of a sca...
Scheme 4: (A) Known biological activities related to sulfur-containing compounds; (B and C) an example of a s...
Scheme 5: (A) Known biological activities related to aminoindane derivatives; (B and C) an example of a scand...
Scheme 6: (A) Known biological activities related to norbornane derivatives; (B and C) an example of a scandi...
Scheme 7: (A) Known biological activities related to aniline derivatives; (B and C) an example of a titanium-...
Scheme 8: (A) Known biological activities related to cyclohexylamine derivatives; (B) an example of an intram...
Scheme 9: (A) Known biologically active benzophenone derivatives; (B and C) photocatalytic oxidation of benzy...
Scheme 10: (A) Known bioactive fluorine-containing compounds; (B and C) vanadium-mediated C(sp3)–H fluorinatio...
Scheme 11: (A) Known biologically active Lythraceae alkaloids; (B) synthesis of (±)-decinine (30).
Scheme 12: (A) Synthesis of (R)- and (S)-boehmeriasin (31); (B) synthesis of phenanthroindolizidines by vanadi...
Scheme 13: (A) Known bioactive BINOL derivatives; (B and C) vanadium-mediated oxidative coupling of 2-naphthol...
Scheme 14: (A) Known antiplasmodial imidazopyridazines; (B) practical synthesis of 41.
Scheme 15: (A) Gold-catalyzed drug-release mechanism using 2-alkynylbenzamides; (B and C) chromium-mediated al...
Scheme 16: (A) Examples of anti-inflammatory benzaldehyde derivatives; (B and C) chromium-mediated difunctiona...
Scheme 17: (A and B) Manganese-catalyzed chemoselective intramolecular C(sp3)–H amination; (C) late-stage modi...
Scheme 18: (A and B) Manganese-catalyzed C(sp3)–H amination; (C) late-stage modification of a leelamine deriva...
Scheme 19: (A) Known bioactive compounds containing substituted N-heterocycles; (B and C) manganese-catalyzed ...
Scheme 20: (A) Known indoles that present GPR40 full agonist activity; (B and C) manganese-catalyzed C–H alkyl...
Scheme 21: (A) Examples of known biaryl-containing drugs; (B and C) manganese-catalyzed C–H arylation through ...
Scheme 22: (A) Known zidovudine derivatives with potent anti-HIV properties; (B and C) manganese-catalyzed C–H...
Scheme 23: (A and B) Manganese-catalyzed C–H organic photo-electrosynthesis; (C) late-stage modification.
Scheme 24: (A) Example of a known antibacterial silylated dendrimer; (B and C) manganese-catalyzed C–H silylat...
Scheme 25: (A and B) Fe-based small molecule catalyst applied for selective aliphatic C–H oxidations; (C) late...
Scheme 26: (A) Examples of naturally occurring gracilioethers; (B) the first total synthesis of gracilioether ...
Scheme 27: (A and B) Selective aliphatic C–H oxidation of amino acids; (C) late-stage modification of proline-...
Scheme 28: (A) Examples of Illicium sesquiterpenes; (B) first chemical synthesis of (+)-pseudoanisatin (80) in...
Scheme 29: (A and B) Fe-catalyzed deuteration; (C) late-stage modification of pharmaceuticals.
Scheme 30: (A and B) Biomimetic Fe-catalyzed aerobic oxidation of methylarenes to benzaldehydes (PMHS, polymet...
Scheme 31: (A) Known tetrahydroquinolines with potential biological activities; (B and C) redox-selective Fe c...
Scheme 32: (A) Known drugs containing a benzofuran unit; (B and C) Fe/Cu-catalyzed tandem O-arylation to acces...
Scheme 33: (A) Known azaindolines that act as M4 muscarinic acetylcholine receptor agonists; (B and C) intramo...
Scheme 34: (A) Known indolinones with anticholinesterase activity; (B and C) oxidative C(sp3)–H cross coupling...
Scheme 35: (A and B) Cobalt-catalyzed C–H alkenylation of C-3-peptide-containing indoles; (C) derivatization b...
Scheme 36: (A) Cobalt-Cp*-catalyzed C–H methylation of known drugs; (B and C) scope of the o-methylated deriva...
Scheme 37: (A) Known lasalocid A analogues; (B and C) three-component cobalt-catalyzed C–H bond addition; (D) ...
Scheme 38: (A and B) Cobalt-catalyzed C(sp2)–H amidation of thiostrepton.
Scheme 39: (A) Known 4H-benzo[d][1,3]oxazin-4-one derivatives with hypolipidemic activity; (B and C) cobalt-ca...
Scheme 40: (A and B) Cobalt-catalyzed C–H arylation of pyrrole derivatives; (C) application for the synthesis ...
Scheme 41: (A) Known 2-phenoxypyridine derivatives with potent herbicidal activity; (B and C) cobalt-catalyzed...
Scheme 42: (A) Natural cinnamic acid derivatives; (B and C) cobalt-catalyzed C–H carboxylation of terminal alk...
Scheme 43: (A and B) Cobalt-catalyzed C–H borylation; (C) application to the synthesis of flurbiprofen.
Scheme 44: (A) Benzothiazoles known to present anticonvulsant activities; (B and C) cobalt/ruthenium-catalyzed...
Scheme 45: (A and B) Cobalt-catalyzed oxygenation of methylene groups towards ketone synthesis; (C) synthesis ...
Scheme 46: (A) Known anticancer tetralone derivatives; (B and C) cobalt-catalyzed C–H difluoroalkylation of ar...
Scheme 47: (A and B) Cobalt-catalyzed C–H thiolation; (C) application in the synthesis of quetiapine (153).
Scheme 48: (A) Known benzoxazole derivatives with anticancer, antifungal, and antibacterial activities; (B and...
Scheme 49: (A and B) Cobalt-catalyzed C–H carbonylation of naphthylamides; (C) BET inhibitors 158 and 159 tota...
Scheme 50: (A) Known bioactive pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives; (B and C) cobalt-catalyzed C–H ...
Scheme 51: (A) Known antibacterial cyclic sulfonamides; (B and C) cobalt-catalyzed C–H amination of propargyli...
Scheme 52: (A and B) Cobalt-catalyzed intramolecular 1,5-C(sp3)–H amination; (C) late-stage functionalization ...
Scheme 53: (A and B) Cobalt-catalyzed C–H/C–H cross-coupling between benzamides and oximes; (C) late-state syn...
Scheme 54: (A) Known anticancer natural isoquinoline derivatives; (B and C) cobalt-catalyzed C(sp2)–H annulati...
Scheme 55: (A) Enantioselective intramolecular nickel-catalyzed C–H activation; (B) bioactive obtained motifs;...
Scheme 56: (A and B) Nickel-catalyzed α-C(sp3)–H arylation of ketones; (C) application of the method using kno...
Scheme 57: (A and B) Nickel-catalyzed C(sp3)–H acylation of pyrrolidine derivatives; (C) exploring the use of ...
Scheme 58: (A) Nickel-catalyzed C(sp3)–H arylation of dioxolane; (B) library of products obtained from biologi...
Scheme 59: (A) Intramolecular enantioselective nickel-catalyzed C–H cycloalkylation; (B) product examples, inc...
Scheme 60: (A and B) Nickel-catalyzed C–H deoxy-arylation of azole derivatives; (C) late-stage functionalizati...
Scheme 61: (A and B) Nickel-catalyzed decarbonylative C–H arylation of azole derivatives; (C) application of t...
Scheme 62: (A and B) Another important example of nickel-catalyzed C–H arylation of azole derivatives; (C) app...
Scheme 63: (A and B) Another notable example of a nickel-catalyzed C–H arylation of azole derivatives; (C) lat...
Scheme 64: (A and B) Nickel-based metalorganic framework (MOF-74-Ni)-catalyzed C–H arylation of azole derivati...
Scheme 65: (A) Known commercially available benzothiophene-based drugs; (B and C) nickel-catalyzed C–H arylati...
Scheme 66: (A) Known natural tetrahydrofuran-containing substances; (B and C) nickel-catalyzed photoredox C(sp3...
Scheme 67: (A and B) Another notable example of a nickel-catalyzed photoredox C(sp3)–H alkylation/arylation; (...
Scheme 68: (A) Electrochemical/nickel-catalyzed C–H alkoxylation; (B) achieved scope, including three using na...
Scheme 69: (A) Enantioselective photoredox/nickel catalyzed C(sp3)–H arylation; (B) achieved scope, including ...
Scheme 70: (A) Known commercially available trifluoromethylated drugs; (B and C) nickel-catalyzed C–H trifluor...
Scheme 71: (A and B) Stereoselective nickel-catalyzed C–H difluoroalkylation; (C) late-stage functionalization...
Scheme 72: (A) Cu-mediated ortho-amination of oxalamides; (B) achieved scope, including derivatives obtained f...
Scheme 73: (A) Electro-oxidative copper-mediated amination of 8-aminoquinoline-derived amides; (B) achieved sc...
Scheme 74: (A and B) Cu(I)-mediated C–H amination with oximes; (C) derivatization using telmisartan (241) as s...
Scheme 75: (A and B) Cu-mediated amination of aryl amides using ammonia; (C) late-stage modification of proben...
Scheme 76: (A and B) Synthesis of purine nucleoside analogues using copper-mediated C(sp2)–H activation.
Scheme 77: (A) Copper-mediated annulation of acrylamide; (B) achieved scope, including the synthesis of the co...
Scheme 78: (A) Known bioactive compounds containing a naphthyl aryl ether motif; (B and C) copper-mediated eth...
Scheme 79: (A and B) Cu-mediated alkylation of N-oxide-heteroarenes; (C) late-stage modification.
Scheme 80: (A) Cu-mediated cross-dehydrogenative coupling of polyfluoroarenes and alkanes; (B) scope from know...
Scheme 81: (A) Known anticancer acrylonitrile compounds; (B and C) Copper-mediated cyanation of unactivated al...
Scheme 82: (A) Cu-mediated radiofluorination of 8-aminoquinoline-derived aryl amides; (B) achieved scope, incl...
Scheme 83: (A) Examples of natural β-carbolines; (B and C) an example of a zinc-catalyzed C–H functionalizatio...
Scheme 84: (A) Examples of anticancer α-aminophosphonic acid derivatives; (B and C) an example of a zinc-catal...
Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124
Graphical Abstract
Figure 1: Schematic overview of fungal interactions in the environment. Fungi can be found in essentially all...
Figure 2: Fungal derived bioactive natural compounds with ecological and/or economic relevance.
Figure 3: Gliotoxin biosynthetic gene cluster and it major biosynthetic transformations: Gliotoxin (5) is the...
Figure 4: Amoebicidal secondary metabolites trypacidin and fumagillin of Aspergillus fumigatus.
Figure 5: Intermediates of the DHN-melanin biosynthesis in Aspergillus fumigatus.
Figure 6: Intermediates and products of the fumigaclavine C biosynthesis.
Figure 7: Bioactive secondary metabolites of Aspergillus fumigatus.
Figure 8: Helvolic acid gene cluster of A. fumigatus.
Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122
Graphical Abstract
Scheme 1: Mn-catalyzed late-stage fluorination of sclareolide (1) and complex steroid 3.
Figure 1: Proposed reaction mechanism of C–H fluorination by a manganese porphyrin catalyst.
Scheme 2: Late-stage radiofluorination of biologically active complex molecules.
Figure 2: Proposed mechanism of C–H radiofluorination.
Scheme 3: Late-stage C–H azidation of bioactive molecules. a1.5 mol % of Mn(TMP)Cl (5) was used. bMethyl acet...
Figure 3: Proposed reaction mechanism of manganese-catalyzed C–H azidation.
Scheme 4: Mn-catalyzed late-stage C–H azidation of bioactive molecules via electrophotocatalysis. a2.5 mol % ...
Figure 4: Proposed reaction mechanism of electrophotocatalytic azidation.
Scheme 5: Manganaelectro-catalyzed late-stage azidation of bioactive molecules.
Figure 5: Proposed reaction pathway of manganaelectro-catalyzed late-stage C–H azidation.
Scheme 6: Mn-catalyzed late-stage amination of bioactive molecules. a3 Å MS were used. Protonation with HBF4⋅...
Figure 6: Proposed mechanism of manganese-catalyzed C–H amination.
Scheme 7: Mn-catalyzed C–H methylation of heterocyclic scaffolds commonly found in small-molecule drugs. aDAS...
Scheme 8: Examples of late-stage C–H methylation of bioactive molecules. aDAST activation. bFor insoluble sub...
Scheme 9: A) Mn-catalyzed late-stage C–H alkynylation of peptides. B) Intramolecular late-stage alkynylative ...
Figure 7: Proposed reaction mechanism of Mn(I)-catalyzed C–H alkynylation.
Scheme 10: Late-stage Mn-catalyzed C–H allylation of peptides and bioactive motifs.
Scheme 11: Intramolecular C–H allylative cyclic peptide formation.
Scheme 12: Late-stage C–H glycosylation of tryptophan analogues.
Scheme 13: Late-stage C–H glycosylation of tryptophan-containing peptides.
Scheme 14: Late-stage C–H alkenylation of tryptophan-containing peptides.
Scheme 15: A) Late-stage C–H macrocyclization of tryptophan-containing peptides and B) traceless removal of py...
Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119
Graphical Abstract
Figure 1: A systems glycobiology framework to link multi-OMICs data. a) Cell signaling proceeds to trigger TF...
Figure 2: Analysis workflow: ChiP-Seq provides evidence of TF binding to promoter regions with 0 ≤ RP ≤ 1, qu...
Figure 3: Summary of TFs enriched to glycosylation pathways for luminal and basal breast cancer: The TFs foun...
Figure 4: Luminal breast cancer signaling pathway enrichment and glycogene connections. a) TF-to-glycogene co...
Figure 5: Basal breast cancer signaling pathway enrichments and glycogene connections. a) TF-to-glycogene com...
Figure 6: Summary of TF–glycopathway enrichments across all cancer types: TF enrichments to glycopathways acr...
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.
Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86
Graphical Abstract
Scheme 1: General strategy for the enantioselective synthesis of N-containing heterocycles from N-tert-butane...
Scheme 2: Methodologies for condensation of aldehydes and ketones with tert-butanesulfinamides (1).
Scheme 3: Transition models for cis-aziridines and trans-aziridines.
Scheme 4: Mechanism for the reduction of N-tert-butanesulfinyl imines.
Scheme 5: Transition models for the addition of organomagnesium and organolithium compounds to N-tert-butanes...
Scheme 6: Synthesis of 2,2-dibromoaziridines 15 from aldimines 14 and bromoform, and proposed non-chelation-c...
Scheme 7: Diastereoselective synthesis of aziridines from tert-butanesulfinyl imines.
Scheme 8: Synthesis of vinylaziridines 22 from aldimines 14 and 1,3-dibromopropene 23, and proposed chelation...
Scheme 9: Synthesis of vinylaziridines 27 from aldimines 14 and α-bromoesters 26, and proposed transition sta...
Scheme 10: Synthesis of 2-chloroaziridines 28 from aldimines 14 and dichloromethane, and proposed transition s...
Scheme 11: Synthesis of cis-vinylaziridines 30 and 31 from aldimines 14 and bromomethylbutenolide 29.
Scheme 12: Synthesis of 2-chloro-2-aroylaziridines 36 and 32 from aldimines 14, arylnitriles 34, and silyldich...
Scheme 13: Synthesis of trifluoromethylaziridines 39 and proposed transition state of the aziridination.
Scheme 14: Synthesis of aziridines 42 and proposed state transition.
Scheme 15: Synthesis of 1-substituted 2-azaspiro[3.3]heptanes, 1-phenyl-2-azaspiro[3.4]octane and 1-phenyl-2-a...
Scheme 16: Synthesis of 1-substituted 2,6-diazaspiro[3.3]heptanes 48 from chiral imines 14 and 1-Boc-azetidine...
Scheme 17: Synthesis of β-lactams 52 from chiral imines 14 and dimethyl malonate (49).
Scheme 18: Synthesis of spiro-β-lactam 57 from chiral (RS)-N-tert-butanesulfinyl isatin ketimine 53 and ethyl ...
Scheme 19: Synthesis of β-lactam 60, a precursor of (−)-batzelladine D (61) and (−)-13-epi-batzelladine D (62)...
Scheme 20: Rhodium-catalyzed asymmetric synthesis of 3-substituted pyrrolidines 66 from chiral imine (RS)-63 a...
Scheme 21: Asymmetric synthesis of 1,3-disubstituted isoindolines 69 and 70 from chiral imine 67.
Scheme 22: Asymmetric synthesis of cis-2,5-disubstituted pyrrolidines 73 from chiral imine (RS)-71.
Scheme 23: Asymmetric synthesis of 3-hydroxy-5-substituted pyrrolidin-2-ones 77 from chiral imine (RS)-74.
Scheme 24: Asymmetric synthesis of 4-hydroxy-5-substituted pyrrolidin-2-ones 80 from chiral imines 79.
Scheme 25: Asymmetric synthesis of 3-pyrrolines 82 from chiral imines 14 and ethyl 4-bromocrotonate (81).
Scheme 26: Asymmetric synthesis of γ-amino esters 84, and tetramic acid derivative 86 from chiral imines (RS)-...
Scheme 27: Asymmetric synthesis of α-methylene-γ-butyrolactams 90 from chiral imines (Z,SS)-87 and ethyl 2-bro...
Scheme 28: Asymmetric synthesis of methylenepyrrolidines 92 from chiral imines (RS)-14 and 2-(trimethysilylmet...
Scheme 29: Synthesis of dibenzoazaspirodecanes from cyclic N-tert-butanesulfinyl imines.
Scheme 30: Stereoselective synthesis of cyclopenta[c]proline derivatives 103 from β,γ-unsaturated α-amino acid...
Scheme 31: Stereoselective synthesis of alkaloids (−)-angustureine (107) and (−)-cuspareine (108).
Scheme 32: Stereoselective synthesis of alkaloids (−)-pelletierine (112) and (+)-coniine (117).
Scheme 33: Synthesis of piperidine alkaloids (+)-dihydropinidine (122a), (+)-isosolenopsin (122b) and (+)-isos...
Scheme 34: Stereoselective synthesis of the alkaloids(+)-sedamine (125) from chiral imine (SS)-119.
Scheme 35: Stereoselective synthesis of trans-5-hydroxy-6-substituted-2-piperidinones 127 and 129 from chiral ...
Scheme 36: Stereoselective synthesis of trans-5-hydroxy-6-substituted ethanone-2-piperidinones 132 from chiral...
Scheme 37: Stereoselective synthesis of trans-3-benzyl-5-hydroxy-6-substituted-2-piperidinones 136 from chiral...
Scheme 38: Stereoselective synthesis of trans-5-hydroxy-6-substituted 2-piperidinones 139 from chiral imine 138...
Scheme 39: Stereoselective synthesis of ʟ-hydroxypipecolic acid 145 from chiral imine 144.
Scheme 40: Synthesis of 1-substituted isoquinolones 147, 149 and 151.
Scheme 41: Stereoselective synthesis of 3-substituted dihydrobenzo[de]isoquinolinones 154.
Scheme 42: Enantioselective synthesis of alkaloids (S)-1-benzyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (...
Scheme 43: Enantioselective synthesis of alkaloids (−)-cermizine B (171) and (+)-serratezomine E (172) develop...
Scheme 44: Stereoselective synthesis of (+)-isosolepnosin (177) and (+)-solepnosin (178) from homoallylamine d...
Scheme 45: Stereoselective synthesis of tetrahydroquinoline derivatives 184, 185 and 187 from chiral imines (RS...
Scheme 46: Stereoselective synthesis of pyridobenzofuran and pyridoindole derivatives 193 from homopropargylam...
Scheme 47: Stereoselective synthesis of 2-substituted 1,2,5,6-tetrahydropyridines 196 from chiral imines (RS)-...
Scheme 48: Stereoselective synthesis of 2-substituted trans-2,6-disubstituted piperidine 199 from chiral imine...
Scheme 49: Stereoselective synthesis of cis-2,6-disubstituted piperidines 200, and alkaloid (+)-241D, from chi...
Scheme 50: Stereoselective synthesis of 6-substituted piperidines-2,5-diones 206 and 1,7-diazaspiro[4.5]decane...
Scheme 51: Stereoselective synthesis of spirocyclic oxindoles 210 from chiral imines (RS)-53.
Scheme 52: Stereoselective synthesis of azaspiro compound 213 from chiral imine 211.
Scheme 53: Stereoselective synthesis of tetrahydroisoquinoline derivatives from chiral imines (RS)-214.
Scheme 54: Stereoselective synthesis of (−)-crispine A 223 from chiral imine (RS)-214.
Scheme 55: Synthesis of (−)-harmicine (228) using tert-butanesulfinamide through haloamide cyclization.
Scheme 56: Stereoselective synthesis of tetraponerines T1–T8.
Scheme 57: Stereoselective synthesis of phenanthroindolizidines 246a and (−)-tylophorine (246b), and phenanthr...
Scheme 58: Stereoselective synthesis of indoline, tetrahydroquinoline and tetrahydrobenzazepine derivatives 253...
Scheme 59: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldimine (RS)-79.
Scheme 60: Stereoselective synthesis of (−)-epiquinamide (266) from chiral aldimine (SS)-261.
Scheme 61: Synthesis synthesis of (–)-hippodamine (273) and (+)-epi-hippodamine (272) using chiral sulfinyl am...
Scheme 62: Stereoselective synthesis of (+)-grandisine D (279) and (+)-amabiline (283).
Scheme 63: Stereoselective synthesis of (−)-epiquinamide (266) and (+)-swaisonine (291) from aldimine (SS)-126....
Scheme 64: Stereoselective synthesis of (+)-C(9a)-epi-epiquinamide (294).
Scheme 65: Stereoselective synthesis of (+)-lasubine II (298) from chiral aldimine (SS)-109.
Scheme 66: Stereoselective synthesis of (−)-epimyrtine (300a) and (−)-lasubine II (ent-302) from β-amino keton...
Scheme 67: Stereoselective synthesis of (−)-tabersonine (310), (−)-vincadifformine (311), and (−)-aspidospermi...
Scheme 68: Stereoselective synthesis of (+)-epohelmin A (258) and (+)-epohelmin B (260) from aldehyde 313 and ...
Scheme 69: Total synthesis of (+)-lysergic acid (323) from N-tert-butanesulfinamide (RS)-1.
Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81
Graphical Abstract
Figure 1: Structures and numbering of berberine (1a), berberrubine (1b) and 9-O-aryl-substituted berberine de...
Scheme 1: Synthesis of 10-O-arylated berberine derivatives 5a–e.
Scheme 2: Cu2+-catalyzed demethylation of berberrubine (1b).
Figure 2: Temperature dependent emission spectra of derivatives 5a and 5d (c = 10 µM, with 0.25% v/v DMSO) in...
Figure 3: Photometric titration of 5a (A) and 5d (B) (cLigand = 20 μM) with ct DNA (1) in BPE buffer (cNa+ = ...
Figure 4: Fluorimetric titration of 5a (A) and 5d (B, cLigand = 20 μM) with ct DNA (1) in BPE buffer (cNa+ = ...
Figure 5: CD and LD spectra of ct DNA (1 and 2, cDNA = 20 μM; in BPE buffer: 10 mM, pH 7.0; with 5% v/v DMSO)...
Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76
Graphical Abstract
Figure 1: Structures of the chemically modified oligonucleotides (A) N3' → P5' phosphoramidate linkage, (B) a...
Scheme 1: Synthesis of a N3' → P5' phosphoramidate linkage by solid-phase synthesis. (a) dichloroacetic acid;...
Figure 2: Crystal structures of (A) N3' → P5' phosphoramidate DNA (PDB ID 363D) [71] and (B) amide (AM1) RNA in c...
Scheme 2: Synthesis of a phosphorodithioate linkage by solid-phase synthesis. (a) detritylation; (b) tetrazol...
Figure 3: Close-up view of a key interaction between the PS2-modified antithrombin RNA aptamer and thrombin i...
Scheme 3: Synthesis of the (S)-GNA thymine phosphoramidite from (S)-glycidyl 4,4'-dimethoxytrityl ether. (a) ...
Figure 4: Surface models of the crystal structures of RNA dodecamers with single (A) (S)-GNA-T (PDB ID 5V1L) [54]...
Figure 5: Structures of 2'-O-alkyl modifications. (A) 2'-O-methoxy RNA (2'-OMe RNA), (B) 2'-O-(2-methoxyethyl...
Scheme 4: Synthesis of the 2'-OMe uridine from 3',5'-O-(tetraisopropyldisiloxane-1,3-diyl)uridine. (a) Benzoy...
Scheme 5: Synthesis of the 2'-O-MOE uridine from uridine. (a) (PhO)2CO, NaHCO3, DMA, 100 °C; (b) Al(OCH2CH2OCH...
Figure 6: Structure of 2'-O-(2-methoxyethyl)-RNA (MOE-RNA). (A) View into the minor groove of an A-form DNA d...
Figure 7: Structures of locked nucleic acids (LNA)/bridged nucleic acids (BNA) modifications. (A) LNA/BNA, (B...
Scheme 6: Synthesis of the uridine LNA phosphoramidite. (a) i) NaH, BnBr, DMF, ii) acetic anhydride, pyridine...
Scheme 7: Synthesis of the 2'-fluoroarabinothymidine. (a) 30% HBr in acetic acid; (b) 2,4-bis-O-(trimethylsil...
Figure 8: Sugar puckers of arabinose (ANA) and arabinofluoro (FANA) nucleic acids compared with the puckers o...
Figure 9: Structures of C4'-modified nucleic acids. (A) 4'-methoxy, (B) 4'-(2-methoxyethoxy), (C) 2',4'-diflu...
Scheme 8: Synthesis of the 4'-F-rU phosphoramidite. (a) AgF, I2, dichloromethane, tetrahydrofuran; (b) NH3, m...
Scheme 9: Synthesis of the thymine FHNA phosphoramidite. (a) thymine, 1,8-diazabicyclo[5.4.0]undec-7-ene, ace...
Scheme 10: Synthesis of the thymine Ara-FHNA phosphoramidite. (a) i) trifluoromethanesulfonic anhydride, pyrid...
Figure 10: Crystal structures of (A) FHNA and (B) Ara-FHNA in modified A-form DNA decamers (PDB IDs 3Q61 and 3...
Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51
Graphical Abstract
Scheme 1: Volatile allyl sulfides. A) Compounds known from garlic oil, B) mechanism of formation from alliin (...
Scheme 2: Degradation of DMSP by marine bacteria. A) Hydrolysis or lysis to DMS, B) demethylation pathway lea...
Scheme 3: Synthesis of DMSP derivatives.
Figure 1: Sulfur volatiles released by agar plate cultures of marine bacteria fed with DAllSP or AllMSP.
Figure 2: Total ion chromatograms of CLSA extracts obtained from feeding experiments with DAllSP fed to A) P....
Scheme 4: Proposed mechanisms for the formation of sulfur volatiles from DAllSP and AllMSP.
Figure 3: EI mass spectrum and fragmentation pattern of the unknown volatiles A) methyl 3-(allyldisulfanyl)pr...
Scheme 5: Synthesis of A) methyl 3-(allyldisulfanyl)propanoate (26) and B) methyl 3-(methylsulfonyl)propanoat...
Figure 4: Total ion chromatograms of CLSA extracts obtained from the feeding experiments with AllMSP fed to A...
Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8
Graphical Abstract
Scheme 1: Synthetic routes towards perfluoroalkyl thioethers.
Scheme 2: Two-step synthesis of BT-SRF reagents from MBT.
Scheme 3: Plausible mechanism for the formation of thioether 3 and thionoester 4.
Scheme 4: Scope of the deoxygenative perfluoroalkylthiolation reaction using BT-SC2F5 and BT-SC3F7.
Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7
Graphical Abstract
Figure 1: The inthomycins A–C (1–3) and structurally closely related compounds.
Figure 2: Syntheses of inthomycins A–C (1–3).
Scheme 1: The first total synthesis of racemic inthomycin A (rac)-1 by Whiting.
Scheme 2: Moloney’s synthesis of the phenyl analogue of inthomycin C ((rac)-3).
Scheme 3: Moloney’s synthesis of phenyl analogues of inthomycins A (rac-1) and B (rac-2).
Scheme 4: The first total synthesis of inthomycin B (+)-2 by R. J. K. Taylor.
Scheme 5: R. J. K. Taylor’s total synthesis of racemic inthomycin A (rac)-1.
Scheme 6: The first total synthesis of inthomycin C ((+)-3) by R. J. K. Taylor.
Scheme 7: The first total synthesis of naturally occurring inthomycin C ((–)-3) by Ryu et al.
Scheme 8: Preparation of E,E-iododiene (+)-84 and Z,E- iododiene 85a.
Scheme 9: Hatakeyama’s total synthesis of inthomycin A (+)-1 and inthomycin B (+)-2.
Scheme 10: Hatakeyama’s total synthesis of inthomycin C ((–)-3).
Scheme 11: Maulide’s formal synthesis of racemic inthomycin C ((rac)-3).
Scheme 12: Hale’s synthesis of dienylstannane (+)-69 and enyne (+)-82b intermediates.
Scheme 13: Hale’s total synthesis of inthomycin C ((+)-3).
Scheme 14: Hale and Hatakeyama’s resynthesis of (3R)-inthomycin C (−)-3 Mosher esters.
Scheme 15: Reddy’s formal syntheses of inthomycin C (+)-3 and inthomycin C ((−)-3).
Scheme 16: Synthesis of the cross-metathesis precursors (rac)-118 and 121.
Scheme 17: Donohoe’s total synthesis of inthomycin C ((−)-3).
Scheme 18: Synthesis of dienylboronic ester (E,E)-128.
Scheme 19: Synthesis of the alkenyl iodides (Z)- and (E)-130.
Scheme 20: Burton’s total synthesis of inthomycin B ((+)-2).
Scheme 21: Burton’s total synthesis of inthomycin C ((−)-3).
Scheme 22: Burton’s total synthesis of inthomycin A ((+)-1).
Scheme 23: Synthesis of common intermediate (Z)-(+)-143a.
Scheme 24: Synthesis of (Z)-and (E)-selective fragments (+)-145a–c.
Scheme 25: Kim’s total synthesis of inthomycins A (+)-1 and B (+)-2.
Scheme 26: Completion of total synthesis of inthomycin C ((–)-3) by Kim.
Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251
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...
Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212
Graphical Abstract
Scheme 1: General scheme of the suggested synthesis of nucleosides employing the enzymatic phosphorolysis of ...
Figure 1: Phosphorolysis (5.0 mM K-phosphate buffer, pH 7.0; 23 °C) of Ara-U and thymidine (Thd) catalyzed by...
Scheme 2: Transarabinosylation of O6-methylguanine (OMG) employing Ara-U as a donor of the Ara-1Pi (1:1.5 mol...
Figure 2: Optimized conditions of phosphorolysis of Ara-U: 0.20 mmol of Ara-U in distilled water (30 mL) cont...
Scheme 3: Synthesis of nelarabine with intermediate preparation of crude Ara-1Pi.
Scheme 4: Synthesis of kinetin riboside with intermediate preparation of crude Rib-1Pi.
Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203
Graphical Abstract
Figure 1: Ligands targeting charged areas on protein surfaces discussed in this review. The protein shown as ...
Figure 2: 1H NMR titration of lysine with tweezers. All signals show chemical shift perturbations and differe...
Figure 3: 1H,15N-HSQC Titration of full-length hPin1 with supramolecular tweezers (original data). (a) Spectr...
Figure 4: Relative signal intensities can be used to identify ligand binding sites (schematic representation ...
Figure 5: Schematic 1H,15N-HSQC spectrum of tauF4 (chemical shifts from BMRB # 17945, [109]) with and without spec...
Figure 6: H2(C)N spectra specific for arginine (a) and lysine (b) residues of the hPin1-WW domain at differen...