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Search for "divergent" in Full Text gives 103 result(s) in Beilstein Journal of Organic Chemistry.
Switchable molecular tweezers: design and applications
- Pablo Msellem,
- Maksym Dekthiarenko,
- Nihal Hadj Seyd and
- Guillaume Vives
Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45
Graphical Abstract
Figure 1: Principle of switchable molecular tweezers.
Figure 2: Principle of pH-switchable molecular tweezers 1 [19].
Figure 3: a) pH-Switchable tweezers 2 substituted with alkyl chains as switchable lipids. b) Schematic depict...
Figure 4: Modification of spectral properties of 3 by controlled induction of Pt–Pt interactions.
Figure 5: Conformational switching of di(hydroxyphenyl)pyrimidine-based tweezer 4 upon alkylation or fluoride...
Figure 6: Hydrazone-based pH-responsive tweezers 5 for mesogenic modulation.
Figure 7: pH-Switchable molecular tweezers 6 bearing acridinium moieties.
Figure 8: a) Terpyridine and pyridine-hydrazone-pyridine analogs molecular tweezers and b) extended pyridine ...
Figure 9: Terpyridine-based molecular tweezers with M–salphen arms and their field of application. Figure 9 was adapt...
Figure 10: a) Terpyridine-based molecular tweezers for diphosphate recognition [48]; b) bishelicene chiroptical te...
Figure 11: Terpyridine-based molecular tweezers with allosteric cooperative binding.
Figure 12: Terpyridine-based molecular tweezers presenting closed by default conformation.
Figure 13: Pyridine-pyrimidine-pyridine-based molecular tweezers.
Figure 14: Coordination-responsive molecular tweezers based on nitrogen-containing ligands.
Figure 15: Molecular tweezers exploiting the remote bipyridine or pyridine binding to trigger the conformation...
Figure 16: Bipyridine-based molecular tweezers exploiting the direct s-trans to s-cis-switching for a) anion b...
Figure 17: a) Podand-based molecular tweezers [66,67]. b) Application of tweezers 32 for the catalytic allosteric reg...
Figure 18: Anion-triggered molecular tweezers based on calix[4]pyrrole.
Figure 19: Anion-triggered molecular tweezers.
Figure 20: a) Principle of the weak link approach (WLA) developed by Mirkin and its application to b) symmetri...
Figure 21: Molecular tweezers as allosteric catalyst in asymmetric epoxide opening [80].
Figure 22: Allosteric regulation of catalytic activity in ring-opening polymerization with double tweezers 41.
Figure 23: a) Conformational switching of 42 by intramolecular –S–S– bridge formation. b) Shift of conformatio...
Figure 24: a) Redox-active glycoluril-TTF tweezers 44. b) Mechanism of stepwise oxidation of said tweezers wit...
Figure 25: Mechanism of formation of the mixed-valence dimers of tweezers 45.
Figure 26: Mechanism of carbohydrate liberation upon redox-mediated conformation switching of 46.
Figure 27: a) The encapsulation properties of 47 as well as the DCTNF release process from its host–guest comp...
Figure 28: Redox-active bipyridinium-based tweezers. a) With a ferrocenyl hinge 49, b) with a propyl hinge 50 ...
Figure 29: Redox-active calix[4]arene porphyrin molecular tweezers.
Figure 30: a) Mechanism of the three orthogonal stimuli. b) Cubic scheme showing the eight different states of ...
Figure 31: Redox-controlled molecular gripper based on a diquinone resorcin[4]arene.
Figure 32: a) Shinkai's butterfly tweezers and their different host–guest properties depending on the isomer. ...
Figure 33: Cyclam-tethered tweezers and their different host–guest complexes depending on their configuration.
Figure 34: Azobenzene-based catalytic tweezers.
Figure 35: Photoswitchable PIEZO channel mimic.
Figure 36: Stilbene-based porphyrin tweezers for fullerene recognition.
Figure 37: Stiff-stilbene-based tweezers with urea or thiourea functional units for a) anion binding, b) anion...
Figure 38: Feringa’s photoswitchable organocatalyst (a) and different catalyzed reactions with that system (b)....
Figure 39: a) Irie and Takeshita’s thioindigo-based molecular tweezers. b) Family of hemithioindigo-based mole...
Figure 40: Dithienylethylene crown ether-bearing molecular tweezers reported by Irie and co-workers.
Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination
- Ruichen Lan,
- Brock Yager,
- Yoonsun Jee,
- Cynthia S. Day and
- Amanda C. Jones
Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43
- with alkene but also the urea carbonyl. The Bronsted acidity of the urea would be increased by coordination to gold, and if such coordination is key to enabling reactivity, this would confirm the higher reactivity of urea 1a. The divergent behavior of sulfonamide 1d does not find an easy explanation
Graphical Abstract
Scheme 1: Proposed mechanism and observation of alkylgold intermediates.
Figure 1: First order alkene decay for urea alkene 1a (0.05 M) hydroamination with [JPhosAu(NCCH3)]SbF6 (5, 2...
Figure 2: Cooperative effect of mixed CD2Cl2/MeOH on alkene 1a → 3a conversion with catalyst 5 (2.5 mol %). E...
Figure 3: Different additive impact on rate of 1a → 3a depending upon catalyst and co-solvent. The data for J...
Figure 4: (a) Schematic for synthesis of [L–Au–L]SbF6 where L = JPhos. (b) Perspective drawing of the cation ...
Figure 5: (a) kobs for reaction of urea 1a (0.05 M) in DCM with catalyst 5 and titrated CH3OH/CH3OD. Data for...
Figure 6: Rate of urea 1a (0.05 M) hydroamination with JPhosAu(NCCH3)SbF6 (2.5 mol %) in CH2Cl2 with 5, 25, a...
Figure 7: Observed rates for the reaction of carbamate 1b (0.03–0.24 M) with JackiephosAuNTf2 (0.0013 M, 6a) ...
Figure 8: Influence of catalyst 5 concentration on rate of 1a (0.05 M in CH2Cl2 with 0, 10 μL MeOH). Error ba...
Scheme 2: Proposed alternate mechanism.
Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin
- Jon Lundstrøm,
- Emilie Gillon,
- Valérie Chazalet,
- Nicole Kerekes,
- Antonio Di Maio,
- Ten Feizi,
- Yan Liu,
- Annabelle Varrot and
- Daniel Bojar
Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31
- , by extension, common folds [12]. Still, shared binding specificity does not always follow from structural similarity, exemplified by divergent evolution within lectin families as well as independent emergence of similar binding patterns [13]. Many of the most commonly used lectins for the
Graphical Abstract
Figure 1: Characterizing a new lectin from the melon Cucumis melo. (a) Evolutionary relationships of common R...
Figure 2: Characterizing the binding specificity of CMA1. (a, b) Lectin produced in mammalian cells was analy...
Figure 3: Assessing and quantifying in-solution binding of CMA1. (a) Erythrocyte agglutination assay. Using r...
Figure 4: Structural insights into the binding mechanism of CMA1. (a, b) Overall representation of the N-term...
Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes
- Michio Yamada
Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13
Graphical Abstract
Scheme 1: Pathway of the [2 + 2] CA–RE reaction of an electron-rich alkyne with TCNE or TCNQ. EDG = electron-...
Scheme 2: Reaction pathway for DMA-appended acetylene and TCNEO.
Scheme 3: Pathway of the [2 + 2] CA–RE reaction between 1 and DCFs.
Scheme 4: Sequential double [2 + 2] CA–RE reactions between 1 and TCNE.
Scheme 5: Divergent chemical transformation pathways of TCBD 6.
Scheme 6: Synthesis of 12.
Scheme 7: [2 + 2] CA–RE reaction of 1 with 14. TCE = 1,1,2,2-tetrachloroethane.
Scheme 8: Autocatalytic model proposed by Nielsen et al.
Scheme 9: Synthesis of anthracene-embedded TCBD compound 19.
Scheme 10: Sequence of the [2 + 2] CA–RE reaction between dibenzo-fused cyclooctyne or cyclooctadiyne and TCNE...
Scheme 11: [2 + 2] CA–RE reaction between the CPP derivatives and TCNE. THF = tetrahydrofuran.
Scheme 12: [2 + 2] CA–RE reaction between ethynylfullerenes 31 and TCNE and subsequent thermal rearrangement.
Scheme 13: Pathway of the [2 + 2] CA–RE reaction between TCNE and 34, followed by additional skeletal transfor...
Scheme 14: Synthesis scheme for heterocycle 38 from the reaction between TCNE and 1 in water and a surfactant.
Scheme 15: Synthesis scheme of the CDA product 41.
Scheme 16: Synthesis of rotaxanes 44 and 46 via the [2 + 2] CA–RE reaction.
Scheme 17: Synthesis of a CuI bisphenanthroline-based rotaxane 50.
Figure 1: Structures of the chiral push–pull chromophores 51–56.
Figure 2: Structures of the axially chiral TCBD 57 and DCNQ 58 bearing a C60 core.
Figure 3: Structures of the axially chiral SubPc–TCBD–aniline conjugates 59 and 60 and the subporphyrin–TCBD–...
Figure 4: Structures of 63 and the TCBD 64.
Figure 5: Structures of the fluorophore-containing TCBDs 65–67.
Figure 6: Structures of the fluorophore-containing TCBDs 68–72.
Figure 7: Structures of the urea-containing TCBDs 73–75.
Figure 8: Structures of the fullerene–TCBD and DCNQ conjugates 76–79 and their reference compounds 80–83.
Figure 9: Structures of the ZnPc–TCBD–aniline conjugates 84 and 85.
Figure 10: Structures of the ZnP–PCBD and TCBD conjugates 86–88.
Figure 11: Structures of the porphyrin-based donor–acceptor conjugates (89–104).
Figure 12: Structures of the porphyrin–PTZ or DMA conjugates 105–112.
Figure 13: Structures of the BODIPY–Acceptor–TPA or PTZ conjugates 113–116.
Figure 14: Structures of the corrole–TCBD conjugates 117 and 118.
Figure 15: Structure of the dendritic TCBD 119.
Figure 16: Structures of the TCBDs 120–126.
Figure 17: Structures of the precursor 127 and TCBDs 128–130.
Figure 18: Structures of 131–134 utilized for BHJ OSCs.
Radical chemistry in polymer science: an overview and recent advances
- Zixiao Wang,
- Feichen Cui,
- Yang Sui and
- Jiajun Yan
Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116
- inextricably linked to organic chemistry. However, the two fields took divergent paths over the past century. Many emergent radical chemistries in the organic chemistry community has not yet found a place in the polymer science. We believe this gap will narrow with a broader use of chemical informatics tools
Graphical Abstract
Scheme 1: Oxidation of catechol and subsequent cross-linking. Scheme 1 redrawn from [3].
Scheme 2: (A) Structure of typical urushiol in Chinese lacquer, and (B) schematic process of laccase-catalyze...
Scheme 3: A) Primary amino acid sequence of mfp-1, mfp-3, and mfp-5 (Y: DOPA, K: lysine). B) Scheme showing e...
Scheme 4: Activation–deactivation equilibrium in nitroxide-mediated polymerizations. Bicomponent initiating s...
Scheme 5: Mechanism of a transition metal complex-mediated ATRP. Scheme 5 redrawn from [14].
Scheme 6: Mechanism of RAFT polymerization. Scheme 6 redrawn from [68].
Scheme 7: Degenerative transfer (a) and reversible termination (b) mechanism of OMRP. Scheme 7 redrawn from [70].
Scheme 8: Simplified mechanism of a RITP. Scheme 8 redrawn from [21].
Scheme 9: (A) Structures of π-conjugated conductive polymers. (B) Examples of conductive polymer synthesis vi...
Scheme 10: Possible regiochemical couplings in PATs. Scheme 10 redrawn from [79].
Scheme 11: General thiol-ene photopolymerization process. Scheme 11 redrawn from [81].
Scheme 12: (a) Three generations of Grubbs catalysts. (b) Proposed mechanism for photo-ROMP via a reductive qu...
Scheme 13: Pyrylium and thiopyrylium salts studied by Boydston et al. Scheme 13 redrawn from [91].
Scheme 14: A general illustration of post-polymerization modification by thiol–ene chemistry.
Scheme 15: Introduction of functionalities by nitroxide radical coupling of HO-TEMPO derivatives.
Scheme 16: Chemical reaction process scheme of DCP-induced crosslinking of LDPE. Scheme 16 redrawn from [126].
Scheme 17: A probable mechanism of radical-induced hydrosilylation.
Scheme 18: Polymer surface modification by homolytic dediazonation of diazonium salts.
Scheme 19: Photoinduced polymer surface modification or surface grafting using benzophenone.
Scheme 20: Depolymerization mechanism of common photoresists. (a) A possible mechanism of radiation decomposit...
Scheme 21: Proposed mechanisms of photooxidative depolymerization of polystyrene. (a) Scheme 21a was reprinted with perm...
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
- applied cell potential. These divergent reactivity features make the two techniques totally complementary, allowing the exploration of a large portion of SET-driven organic transformations using at least one of them at a time. Since ‘radical ion’ conPET/e-PRC are proposed to involve the same radical ion
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.
Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update
- Anup Biswas
Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72
- stereocenter bearing primary amine and trifluoromethyl functionalities associated with appreciable enantiocontrol. The substrate scope was investigated by the variation of sterically and electronically divergent aryl substituents in the ketimines but the enantioselectivity was markedly lowered with sterically
- output of the reaction furnishing the products with moderate to excellent enantioselectivities. Electronically and sterically divergent functionalities in the benzene ring of 49 expanded the substrate scope whereas variation of 115 was very much limited (Scheme 27) [57]. In 2021, Wang and co-workers
- nitrogen and ring nitrogen of 49 were screened under optimal reaction conditions where Cbz and benzyl were the best protecting groups in terms of enantioselectivities. A product library was prepared by varying sterically and electronic divergent functionalities in the carbocyclic rings of both reactants
Graphical Abstract
Scheme 1: First organocatalyzed asymmetric aza-Friedel–Crafts reaction.
Scheme 2: Aza-Friedel–Crafts reaction between indoles and cyclic ketimines.
Scheme 3: Aza-Friedel–Crafts reaction utilizing trifluoromethyldihydrobenzoazepinoindoles as electrophiles.
Scheme 4: Aza-Friedel–Crafts reaction utilizing cyclic N-sulfimines as electrophiles.
Scheme 5: Aza-Friedel–Crafts reaction involving N-unprotected imino ester as electrophile.
Scheme 6: Aza-Friedel–Crafts and lactonization cascade.
Scheme 7: One-pot oxidation and aza-Friedel–Crafts reaction.
Scheme 8: C1 and C2-symmetric phosphoric acids as catalysts.
Scheme 9: Aza-Friedel–Crafts reaction using Nps-iminophosphonates as electrophiles.
Scheme 10: Aza-Friedel–Crafts reaction between indole and α-iminophosphonate.
Scheme 11: [2.2]-Paracyclophane-derived chiral phosphoric acids as catalyst.
Scheme 12: Aza-Friedel–Crafts reaction through ring opening of sulfamidates.
Scheme 13: Isoquinoline-1,3(2H,4H)-dione scaffolds as electrophiles.
Scheme 14: Functionalization of the carbocyclic ring of substituted indoles.
Scheme 15: Aza-Friedel–Crafts reaction between unprotected imines and aza-heterocycles.
Scheme 16: Anilines and α-naphthols as potential nucleophiles.
Scheme 17: Solvent-controlled regioselective aza-Friedel–Crafts reaction.
Scheme 18: Generating central and axial chirality via aza-Friedel–Crafts reaction.
Scheme 19: Reaction between indoles and racemic 2,3-dihydroisoxazol-3-ol derivatives.
Scheme 20: Exploiting 5-aminoisoxazoles as nucleophiles.
Scheme 21: Reaction between unsubstituted indoles and 3-alkynylated 3-hydroxy-1-oxoisoindolines.
Scheme 22: Synthesis of unnatural amino acids bearing an aza-quaternary stereocenter.
Scheme 23: Atroposelective aza-Friedel–Crafts reaction.
Scheme 24: Coupling of 5-aminopyrazole and 3H-indol-3-ones.
Scheme 25: Pyrophosphoric acid-catalyzed aza-Friedel–Crafts reaction on phenols.
Scheme 26: Squaramide-assisted aza-Friedel–Crafts reaction.
Scheme 27: Thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 28: Squaramide-catalyzed reaction between β-naphthols and benzothiazolimines.
Scheme 29: Thiourea-catalyzed reaction between β-naphthol and isatin-derived ketamine.
Scheme 30: Quinine-derived molecule as catalyst.
Scheme 31: Cinchona alkaloid as catalyst.
Scheme 32: aza-Friedel–Crafts reaction by phase transfer catalyst.
Scheme 33: Disulfonamide-catalyzed reaction.
Scheme 34: Heterogenous thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 35: Total synthesis of (+)-gracilamine.
Scheme 36: Total synthesis of (−)-fumimycin.
Strategies in the synthesis of dibenzo[b,f]heteropines
- David I. H. Maier,
- Barend C. B. Bezuidenhoudt and
- Charlene Marais
Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51
- final Mizoroki–Heck reaction will be discussed in the following section. The Buchwald group [59] reported a ligand-controlled divergent synthesis involving intramolecular cyclisation, allowing for the formation of several heterocycles, including dibenzo[b,f]azepines 89, in two steps. Screening of
Graphical Abstract
Figure 1: Dibenzo[b,f]azepine (1a), -oxepine (1b) and -thiepine (1c) as examples of dibenzo[b,f]heteropines (1...
Figure 2: Selected pharmaceuticals with the dibenzo[b,f]azepine skeleton.
Figure 3: Examples of 10,11-dihydrodibenzo[b,f]azepine-based ligands.
Figure 4: The dibenzo[b,f]azepine moiety in dyes with properties suitable for the use in organic light emitti...
Figure 5: Selective bioactive natural products (13–18) containing the dibenzo[b,f]oxepine scaffold and Novart...
Scheme 1: Retrosynthetic approach to 5H-dibenzo[b,f]azepine (1a) from nitrotoluene (22).
Scheme 2: Oxidative coupling of o-nitrotoluene (22) and reduction of 2,2'-dinitrobibenzyl (21) to form 2,2'-d...
Scheme 3: Synthesis of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a) via amine condensation.
Scheme 4: Catalytic reduction of 10,11-dihydro-5H-dibenzo[b,f]azepine (2a).
Scheme 5: The Wagner–Meerwein rearrangement of acridin-9-ylmethanol (23) into 5H-dibenzo[b,f]azepine (1a).
Scheme 6: Oxidative ring expansion of 2-(9-xanthenyl)malonates 24.
Scheme 7: Ring expansion via C–H functionalisation.
Scheme 8: The synthesis of fluorinated 5H-dibenzo[b,f]azepine 38 from isatin (32).
Scheme 9: The synthesis of substituted dibenzo[b,f]azepines 43 from indoles 39.
Scheme 10: Retrosynthetic pathways to dibenzo[b,f]azepines via Buchwald–Hartwig amination.
Scheme 11: Synthesis of dibenzo[b,f]oxepine 54 and -azepine 55 derivatives via (i) Heck reaction and (ii) Buch...
Scheme 12: Double Buchwald–Hartwig amination and thioetherification in the synthesis of tricyclic azepines 60 ...
Scheme 13: Double Buchwald–Hartwig amination towards substituted dibenzoazepines 62.
Scheme 14: Double Buchwald–Hartwig amination towards 10,11-dihydro-5H-dibenzo[b,f]azepine derivatives 71.
Scheme 15: One-pot Suzuki coupling–Buchwald–Hartwig amination.
Scheme 16: One-pot Rh/Pd-catalysed synthesis of dihydropyridobenzazepines.
Scheme 17: A retrosynthetic pathway to dibenzo[b,f]azepines via Mizoroki–Heck reaction.
Scheme 18: One-pot domino Pd-catalyzed Mizoroki–Heck–Buchwald–Hartwig synthesis of dibenzo[b,f]azepines.
Scheme 19: Dibenzo[b,f]thiapine and -oxepine synthesis via SNAr (thio)etherification, Wittig methylenation and...
Scheme 20: A retrosynthetic pathway to dibenzo[b,f]oxepines via Ullmann coupling.
Scheme 21: Ullmann-type coupling in dibenzo[b,f]oxepine synthesis.
Scheme 22: Wittig reaction and Ullmann coupling as key steps in dihydrobenz[b,f]oxepine synthesis.
Scheme 23: Pd-catalysed dibenzo[b,f]azepine synthesis via norbornene azepine intermediate 109.
Scheme 24: A simple representation of olefin metathesis resulting in transalkylidenation.
Scheme 25: Ring-closing metathesis as key step in the synthesis of dibenzo[b,f]heteropines.
Scheme 26: Alkyne–aldehyde metathesis in the synthesis of dibenzo[b,f]heteropines.
Scheme 27: Hydroarylation of 9-(2-alkynylphenyl)-9H-carbazole derivatives.
Scheme 28: Oxidative coupling of bisphonium ylide intermediate to give pacharin (13).
Scheme 29: Preparation of 10,11-dihydrodibenzo[b,f]heteropines via intramolecular Wurtz reaction.
Scheme 30: Phenol deprotonation and intramolecular etherification in the synthesis of bauhinoxepine J.
Figure 6: Functionalisation of dibenzo[b,f]azepine.
Scheme 31: Palladium-catalysed N-arylation of dibenzo[b,f]azepine.
Scheme 32: Cu- and Ni-catalysed N-arylation.
Scheme 33: N-Alkylation of dibenzo[b,f]azepine (1a) and dihydrodibenzo[b,f]azepine (2a).
Scheme 34: Preparation of methoxyiminosilbene.
Scheme 35: Synthesis of oxcarbazepine (153) from methoxy iminostilbene 151.
Scheme 36: Ring functionalisation of dihydrodibenzo[b,f]azepine.
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
- ) [69]. Through a divergent synthetic route, employing as main steps the formation of the diaryl ether through SNAr-type reactions and the macrolide formation using the Mitsunobu reaction, Kim and co-workers [71] synthesized isocorniculatolide B and corniculatolides B and C for further evaluation of
- synthesis of combretastatin D-2 (2) by Rychnovsky and Hwang [36]. Divergent synthesis of (±)-1 form combretastatin D-2 (2) by Rychnovsky and Hwang [36]. Enantioselective synthesis of 1 by Rychnovsky and Hwang employing Jacobsen catalyst [41]. Synthesis of fragment 57 by Couladouros and co-workers [43][45
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].
Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade
- Qian-Ci Gao,
- Yi-Fei Li,
- Jun Xuan and
- Xiao-Qiang Hu
Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10
- recently, the same group developed an efficient Rh(III)-catalyzed C–H cross-coupling of enaminones with diazodicarbonyls for the divergent construction of isocoumarins and naphthalenes [27]. Moreover, Loh et al. disclosed a Rh-catalyzed formal [4 + 2] cycloaddition of enaminones with diazocarbonyls [28
Graphical Abstract
Scheme 1: Significance of isocoumarins (a), classic methods for the synthesis of isocoumarins (b) and reactio...
Scheme 2: Scope of enaminones.
Scheme 3: Scope of iodonium ylides.
Scheme 4: Gram-scale reaction (a) and synthetic transformation (b).
Scheme 5: Proposed mechanism.
Improving the accuracy of 31P NMR chemical shift calculations by use of scaling methods
- William H. Hersh and
- Tsz-Yeung Chan
Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4
- in our hands, in some cases giving widely divergent chemical shifts for the two chemically equivalent phosphorus atoms, which could potentially exacerbate any deviations from the experimental chemical shifts. Since derivatives with methyl (1a) and butyl substitution on PA were reported and had
Graphical Abstract
Figure 1: Training set of tri- and tetracoordinate phosphorus compounds; chemical shifts are in ppm, referenc...
Figure 2: (a) Plot of experimental vs calculated chemical shifts of tri- and tetracoordinate phosphorus compo...
Figure 3: Plot of experimental vs calculated chemical shifts of training set compounds reported by Latypov et...
Figure 4: “Large” compounds selected for 31P NMR calculation by Latypov [37].
Figure 5: Stereoisomers and unusual phosphorus compounds used for chemical shift calculations.
Figure 6: Phosphorus-catalyzed oxygen transfer reaction intermediates.
Figure 7: Phosphirane reactions.
Figure 8: (a) Plot of experimental vs scaled chemical shifts derived from the tri- and tetracoordinate phosph...
Combining the best of both worlds: radical-based divergent total synthesis
- Kyriaki Gennaiou,
- Antonios Kelesidis,
- Maria Kourgiantaki and
- Alexandros L. Zografos
Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1
- of atom economy and protecting-group-free synthesis dominating the field of total synthesis. In this new era, total synthesis is moving towards natural efficacy by utilizing both the biosynthetic knowledge of divergent synthesis and the latest developments in radical chemistry. This contemporary
- ” [8]. And this is where divergent total synthesis might help. Divergent total synthesis is an old but yet underdeveloped strategy, utilizing the conceptual advantages of biosynthetic routes that allow multi-target natural product synthesis through a unified synthetic plan [9][10]. Based on the logic
- of divergent synthesis, common synthetic scaffolds, which are regarded as the points of diversity of the synthetic plan, lie at the heart of retrosynthetic design. Radical disconnections on common scaffolds, in accordance to the trends of green chemistry [11] and the concepts of atom economy [12] and
Graphical Abstract
Scheme 1: The power of radical retrosynthesis and the tactic of divergent total synthesis.
Figure 1: Evolution of radical chemistry for organic synthesis.
Scheme 2: Divergent total synthesis of α-pyrone-diterpenoids (Baran).
Scheme 3: Divergent synthesis of pyrone diterpenoids by merged chemoenzymatic and radical synthesis (part I, ...
Scheme 4: Divergent synthesis of pyrone diterpenoids by merged chemoenzymatic and radical synthesis (part II,...
Scheme 5: Divergent synthesis of drimane-type hydroquinone meroterpenoids (Li).
Scheme 6: Divergent synthesis of natural products isolated from Dysidea avara (Lu).
Scheme 7: Divergent synthesis of kaurene-type terpenoids (Lei).
Scheme 8: Divergent synthesis of 6-oxabicyclo[3.2.1]octane meroterpenoids (Lou).
Scheme 9: Divergent synthesis of crinipellins by radical-mediated Dowd–Backwith rearrangement (Xie and Ding).
Scheme 10: Divergent total synthesis of Galbulimima alkaloids (Shenvi).
Scheme 11: Divergent synthesis of eburnane alkaloids (Qin).
Scheme 12: Divergent synthesis of Aspidosperma alkaloids (Boger).
Scheme 13: Photoredox based synthesis of (−)-FR901483 (160) and (+)-TAN1251C (162, Gaunt).
Scheme 14: Divergent synthesis of bipolamines (Maimone).
Scheme 15: Flow chemistry divergency between aporphine and morphinandione alkaloids (Felpin).
Scheme 16: Divergent synthesis of pyrroloazocine natural products (Echavarren).
Scheme 17: Using TEMPO to stabilize radicals for the divergent synthesis of pyrroloindoline natural products (...
Scheme 18: Radical pathway for preparation of lignans (Zhu).
Scheme 19: Divergent synthesis of DBCOD lignans (Lumb).
Synthesis of (−)-halichonic acid and (−)-halichonic acid B
- Keith P. Reber and
- Emma L. Niner
Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174
- derived from a common biosynthetic pathway starting from farnesyl pyrophosphate and glycine [5]. This prompted us to investigate a biomimetic synthesis in which the halichonic acids could be prepared from a common imine intermediate via divergent intramolecular aza-Prins cyclizations [8]. Herein, we
- acyclic conformational analysis. Three divergent mechanistic pathways can be formulated by considering the different conformers of protonated imine 7, namely iminium ions 12a–c (Scheme 3). In each case, the chair-like transition state of the intramolecular aza-Prins reaction is controlled by the C7
Graphical Abstract
Figure 1: Structures of halichonic acid ((+)-1) and halichonic acid B ((+)-2).
Scheme 1: Synthesis of (−)-7-amino-7,8-dihydrobisabolene (4) and its conversion to cyclization precursor 7.
Scheme 2: Synthesis of the halichonic acids via a key intramolecular aza-Prins cyclization.
Scheme 3: Proposed intermediates for the intramolecular aza-Prins reaction leading to the formation of ethyl ...
Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group
- Chuanhua Qu,
- Run Huang,
- Yong Li,
- Tong Liu,
- Yuan Chen and
- Guiting Song
Beilstein J. Org. Chem. 2021, 17, 2822–2831, doi:10.3762/bjoc.17.193
- 402160, China 10.3762/bjoc.17.193 Abstract Chemoselective sulfonylation and isonitrilation reactions for the divergent synthesis of valuable diarylmethyl sulfones and isonitrile diarylmethanes starting from easy-to-synthesize para-quinone methides (p-QMs) and commercially abundant p
Graphical Abstract
Figure 1: Selected bioactive compounds.
Scheme 1: The chemistry of TosMIC in the reactions with olefins.
Scheme 2: ZnI2-catalyzed C–S-bond cleavage of TosMIC for the synthesis of diarylmethyl sulfones 3a–m. Reactio...
Scheme 3: Cases encountered by other p-QMs examinations.
Figure 2: Crystal structure of diarylmethyl sulfone 3e.
Scheme 4: DBU-catalyzed 1,6-conjugate addition for the synthesis of isonitrile diarylmethanes 4a–h. Reaction ...
Scheme 5: Synthetic applications of the synthesized compound 3b.
Scheme 6: Mechanistic studies and proposed mechanism.
Direct C(sp3)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement
- Siyu Wang,
- Lianyou Zheng,
- Shutao Wang,
- Shulin Ning,
- Zhuoqi Zhang and
- Jinbao Xiang
Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167
- pyridylic C(sp3)–H bond (Scheme 1b). For examples, Tunge et al. developed a Pd-catalyzed intramolecular decarboxylative coupling of heterocyclic ally esters via a tandem allylation/Cope rearrangement strategy [18]; Hartwig and co-workers reported a stereo-divergent allylic substitution with azaarene
Graphical Abstract
Scheme 1: The benzylic C(sp3)–H allylic alkylation reactions of 2-alkylpyridines.
Scheme 2: Mechanistic hypothesis of the alkylation reaction of 2-alkylpyridines with MBH carbonates.
Scheme 3: Scope of MBH carbonates 2 with 2-picoline 1a. The reactions were performed using 1a (1.0 mmol, 2 eq...
Scheme 4: Scope of 2-alkylpyridine 1 with MBH carbonate 2a. The reactions were performed using 1 (1.0 mmol, 2...
Progress and challenges in the synthesis of sequence controlled polysaccharides
- Giulio Fittolani,
- Theodore Tyrikos-Ergas,
- Denisa Vargová,
- Manishkumar A. Chaube and
- Martina Delbianco
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...
On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets
- Renato L. Carvalho,
- Amanda S. de Miranda,
- Mateus P. Nunes,
- Roberto S. Gomes,
- Guilherme A. M. Jardim and
- Eufrânio N. da Silva Júnior
Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126
- efficient antibacterial compounds (Scheme 24A) [146]. In 2021, a divergent silylation of alkenes via a manganese-catalyzed C–H activation was reported by Xie et al. by using a ligand-tuned metalloradical reactivity strategy (Scheme 24B and C) [147]. Using Mn2(CO)10 as a catalyst precursor, the authors
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...
Control over size, shape, and photonics of self-assembled organic nanocrystals
- Chen Shahar,
- Yaron Tidhar,
- Yunmin Jung,
- Haim Weissman,
- Sidney R. Cohen,
- Ronit Bitton,
- Iddo Pinkas,
- Gilad Haran and
- Boris Rybtchinski
Beilstein J. Org. Chem. 2021, 17, 42–51, doi:10.3762/bjoc.17.5
- nanocrystals with a tunable aspect ratio. These systems are quite uniform and exhibit morphology-dependent photonics: strikingly, divergent exciton diffusion properties as a function of the shape. Results and Discussion Following our interest in the self-assembly of PDI derivatives, we employed compound 1, a
Graphical Abstract
Figure 1: Chemical structure of compound 1 and UV–vis spectra in an aggregating aqueous medium and in the dis...
Figure 2: Transmission electron microscopy (TEM) images (left, zoomed-out and zoomed-in; 1 × 10−4 M solutions...
Figure 3: Cryo-TEM images of a 1 × 10−4 M solution of 1 (5% THF) and the corresponding molecular model as wel...
Figure 4: Cryo-TEM images of 1 × 10−4 M compound 1 in THF/water solutions after one minute of aging. A) 5% TH...
Figure 5: Transient kinetics at different laser powers probed at 755 nm (1 × 10−4 M solution at pH 10): A) 5%...
3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia
- Florian Mann,
- Daiane Szczerbowski,
- Lisa de Silva,
- Melanie McClure,
- Marianne Elias and
- Stefan Schulz
Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228
- diversification and species recognition. Yet despite growing interests in this tribe, chemical differentiation between taxa has garnered surprisingly little attention until now. Here we focus on the two closely related taxa, Ithomia salapia aquinia and I. s. derasa. The two subspecies have somewhat divergent wing
Graphical Abstract
Figure 1: Extended hairs (arrow) of the androconia of a male Ithomia salapia aquinia (Photo: Melanie McClure)....
Scheme 1: Pyrrolizidine alkaloid lycopsamine (1) and the putative pheromone compounds methyl hydroxydanaidoat...
Scheme 2: Biosynthetic formation of hedycaryol (7) and α-elemol (8).
Figure 2: Total ion current chromatogram of androconial extracts of male butterflies of the two subspecies I....
Figure 3: Proposed mass spectrometric formation of characteristic ions in prenyl and isoprenyl esters. Format...
Figure 4: Mass spectra and fragmentation of A: isoprenyl (3-methyl-3-butenyl) 9-octadenoate (9) and B: prenyl...
Figure 5: Mass spectra and fragmentation of A: isoprenyl 3-acetoxyoctadecanoate (11); B: isoprenyl (Z)-3-acet...
Scheme 3: Synthesis of isoprenyl 3-acetoxyoctadecanoate (11). a) IBX, EtOAc, 60 °C, 3.15 h, 99%; b) SnCl2, CH2...
Scheme 4: a) 48% HBraq, toluene, 24 h, 110 °C, 79%; b) IBX, EtOAc, 60 °C, 3.15 h, 90%; c) C5H11PPh3Br, LDA, T...
Figure 6: Separation of the enantiomers of methyl (Z)-3-hydroxy-13-octadecenoate (25) on a β-6-TBDMS hydrodex...
Scheme 5: Proposed biosynthetic pathway of fatty acids leading to the observed regioisomers of the isoprenyl ...
Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions
- Shrikant D. Tambe,
- Kwan Hong Min,
- Naeem Iqbal and
- Eun Jin Cho
Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114
- same starting material is a highly attractive divergent approach, though it represents significant synthetic challenges. Recent advances in visible-light photocatalysis, mediated by visible-light-absorbing photosensitizers, have allowed ready access to complex molecules in a controlled manner, where
- , which, in turn, prevents the generation of the α-amino radical C from Cy2NMe, resulting in the homocoupling of B to selectively form the symmetrical diamine product 3a. Conclusion We developed a divergent synthetic approach for the valuable 1,2-diamine motif from N-benzylidene-[1,1'-biphenyl]-2-amines
Graphical Abstract
Scheme 1: Photocatalytic transformations of imines.
Scheme 2: Substrate scope for the radical cross-couplings. Reaction conditions: 1 (0.3 mmol), under argon atm...
Scheme 3: Substrate scope for the homocoupling. Reaction conditions: 1 (0.3 mmol), under argon atmosphere, is...
Scheme 4: Reduction of the imine 1a to the amine 4a.
Scheme 5: Proposed mechanism.
Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole
- Carlos H. Escalante,
- Eder I. Martínez-Mora,
- Carlos Espinoza-Hicks,
- Alejandro A. Camacho-Dávila,
- Fernando R. Ramos-Morales,
- Francisco Delgado and
- Joaquín Tamariz
Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113
- Chihuahua, Circuito Universitario S/N, 31125 Chihuahua, Chih., Mexico Unidad de Servicios de Apoyo en Resolución Analítica, Universidad Veracruzana, Luis Castelazo Ayala S/N, 91190 Xalapa, Ver., Mexico 10.3762/bjoc.16.113 Abstract A highly regio-, chemo- and stereoselective divergent synthesis of isoindolo
Graphical Abstract
Figure 1: Fused aza-hetero polycyclic frames and natural pyrrolizine- and isoindole-containing alkaloids.
Scheme 1: Synthetic approaches for the preparation of pyrrolo-fused aza-hetero polycyclic frames.
Scheme 2: Preparation of 1,2-substituted pyrroles 8a–f and 8i,j.
Scheme 3: Diels–Alder cycloadditions of pyrroles 8a–j and 16a–b with maleimides 7b–c.
Figure 2: Structures of 9m (a) and 10m (b) as determined by single-crystal X-ray diffraction crystallography ...
Scheme 4: Pd(0)-catalyzed intramolecular Heck cross-coupling reaction of 2-vinylpyrroles 8c,d and 8g.
Scheme 5: Synthesis of 2-vinylpyrroles 8k,l and their Pd(0)-catalyzed intramolecular Heck cross-coupling to p...
Scheme 6: Diastereoselective Diels–Alder reaction of pyrrolo[2,1-a]isoindole 18a with 7c.
Scheme 7: Synthetic approach to the fused aza-heterocyclic pentacycle 12.
Figure 3: M06-2X/6-31+G(d,p) Optimized geometry for each of the SCs (a and d), TSs (b and e) and ADs (c and f...
Figure 4: M06-2X/6-31+G(d,p) Optimized geometry for each of the TSs of the Diels–Alder reactions of dienes 8b...
Figure 5: M06-2X/6-31+G(d,p) Optimized geometry of the endo SCs (a) and TSs (b) for the Diels–Alder reaction ...
Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules
- Valerian Dragutan,
- Ileana Dragutan,
- Albert Demonceau and
- Lionel Delaude
Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68
- metathesis (RCM) [67][68]. Starting from 3-cyanocyclohex-2-enone, the authors obtained a versatile intermediate able to provide the appropriate dienyne precursors (A–C, Scheme 4) by multicomponent Grignard addition-alkylations. Through divergent cyclizations involving a chemoselective enyne metathesis
Graphical Abstract
Scheme 1: Intramolecular (A) and intermolecular (B) enyne metathesis reactions.
Scheme 2: Ene–yne and yne–ene mechanisms for intramolecular enyne metathesis reactions.
Scheme 3: Metallacarbene mechanism in intermolecular enyne metathesis.
Scheme 4: The Oguri strategy for accessing artemisinin analogs 1a–c through enyne metathesis.
Scheme 5: Access to the tetracyclic core of nanolobatolide (2) via tandem enyne metathesis followed by an Eu(...
Scheme 6: Synthesis of (−)-amphidinolide E (3) using an intermolecular enyne metathesis as the key step.
Scheme 7: Synthesis of amphidinolide K (4) by an enyne metathesis route.
Scheme 8: Trost synthesis of des-epoxy-amphidinolide N (5) [72].
Scheme 9: Enyne metathesis between the propargylic derivative and the allylic alcohol in the synthesis of the...
Scheme 10: Synthetic route to amphidinolide N (6a).
Scheme 11: Synthesis of the stereoisomeric precursors of amphidinolide V (7a and 7b) through alkyne ring-closi...
Scheme 12: Synthesis of the anthramycin precursor 8 from ʟ-methionine by a tandem enyne metathesis–cross metat...
Scheme 13: Synthesis of (−)‐clavukerin A (9) and (−)‐isoclavukerin A (10) by an enyne metathesis route startin...
Scheme 14: Synthesis of (−)-isoguaiene (11) through an enyne metathesis as the key step.
Scheme 15: Synthesis of erogorgiaene (12) by a tandem enyne metathesis/cross metathesis sequence using the sec...
Scheme 16: Synthesis of (−)-galanthamine (13) from isovanilin by an enyne metathesis.
Scheme 17: Application of enyne metathesis for the synthesis of kempene diterpenes 14a–c.
Scheme 18: Synthesis of the alkaloid (+)-lycoflexine (15) through enyne metathesis.
Scheme 19: Synthesis of the AB subunits of manzamine A (16a) and E (16b) by enyne metathesis.
Scheme 20: Jung's synthesis of rhodexin A (17) by enyne metathesis/cross metathesis reactions.
Scheme 21: Total synthesis of (−)-flueggine A (18) and (+)-virosaine B (19) from Weinreb amide by enyne metath...
Scheme 22: Access to virgidivarine (20) and virgiboidine (21) by an enyne metathesis route.
Scheme 23: Enyne metathesis approach to (−)-zenkequinone B (22).
Scheme 24: Access to C-aryl glycoside 23 by an intermolecular enyne metathesis/Diels–Alder cycloaddition.
Scheme 25: Synthesis of spiro-C-aryl glycoside 24 by a tandem intramolecular enyne metathesis/Diels–Alder reac...
Scheme 26: Pathways to (−)-exiguolide (25) by Trost’s Ru-catalyzed enyne cross-coupling and cross-metathesis [94].
Recent advances in Cu-catalyzed C(sp3)–Si and C(sp3)–B bond formation
- Balaram S. Takale,
- Ruchita R. Thakore,
- Elham Etemadi-Davan and
- Bruce H. Lipshutz
Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67
- PhMe2Si moiety in a 1,4-manner to unsaturated nitro and cyano derivatives leading to adducts 209–218, each being obtained in high chemical yield and good enantioselectivity (Scheme 37). 1.5 Miscellaneous reactions The Tsuji group developed a mild method for the regio-divergent silacarboxylation of allenes
- cyclobutyl boronates in high yields and with excellent stereocontrol [101]. This work followed on the heels of earlier studies on the borylation of 2,6-disubstituted p-quinone methides en route to enantioenriched mono- and dibenzylic boronates [102]. An efficient regio-divergent method starting from a single
- adducts (e.g., 373 to form products, 374 and 375; Scheme 59) highlights the utility of this methodology [109]. Following Hoveyda’s report on enantioselective Cu-catalyzed conjugate additions of borylated butadiene, generated in situ, to enolates [110], Procter et al. described the regio-divergent
Graphical Abstract
Scheme 1: Pharmaceuticals possessing a silicon or boron atom.
Scheme 2: The first Cu-catalyzed C(sp3)–Si bond formation.
Scheme 3: Conversion of benzylic phosphate 6 to the corresponding silane.
Scheme 4: Conversion of alkyl triflates to alkylsilanes.
Scheme 5: Conversion of secondary alkyl triflates to alkylsilanes.
Scheme 6: Conversion of alkyl iodides to alkylsilanes.
Scheme 7: Trapping of intermediate radical through cascade reaction.
Scheme 8: Radical pathway for conversion of alkyl iodides to alkylsilanes.
Scheme 9: Conversion of alkyl ester of N-hydroxyphthalimide to alkylsilanes.
Scheme 10: Conversion of gem-dibromides to bis-silylalkanes.
Scheme 11: Conversion of imines to α-silylated amines (A) and the reaction pathway (B).
Scheme 12: Conversion of N-tosylimines to α-silylated amines.
Scheme 13: Screening of diamine ligands.
Scheme 14: Conversion of N-tert-butylsulfonylimines to α-silylated amines.
Scheme 15: Conversion of aldimines to nonracemic α-silylated amines.
Scheme 16: Conversion of N-tosylimines to α-silylated amines.
Scheme 17: Reaction pathway [A] and conversion of aldehydes to α-silylated alcohols [B].
Scheme 18: Conversion of aldehydes to benzhydryl silyl ethers.
Scheme 19: Conversion of ketones to 1,2-diols (A) and conversion of imines to 1,2-amino alcohols (B).
Scheme 20: Ligand screening (A) and conversion of aldehydes to α-silylated alcohols (B).
Scheme 21: Conversion of aldehydes to α-silylated alcohols.
Scheme 22: 1,4-Additions to α,β-unsaturated ketones.
Scheme 23: 1,4-Additions to unsaturated ketones to give β-silylated derivatives.
Scheme 24: Additions onto α,β-unsaturated lactones to give β-silylated lactones.
Scheme 25: Conversion of α,β-unsaturated to β-silylated lactams.
Scheme 26: Conversion of N-arylacrylamides to silylated oxindoles.
Scheme 27: Conversion of α,β-unsaturated carbonyl compounds to silylated tert-butylperoxides.
Scheme 28: Catalytic cycle for Cu(I) catalyzed α,β-unsaturated compounds.
Scheme 29: Conversion of p-quinone methides to benzylic silanes.
Scheme 30: Conversion of α,β-unsaturated ketimines to regio- and stereocontrolled allylic silanes.
Scheme 31: Conversion of α,β-unsaturated ketimines to enantioenriched allylic silanes.
Scheme 32: Regioselective conversion of dienedioates to allylic silanes.
Scheme 33: Conversion of alkenyl-substituted azaarenes to β-silylated adducts.
Scheme 34: Conversion of conjugated benzoxazoles to enantioenriched β-silylated adducts.
Scheme 35: Conversion of α,β-unsaturated carbonyl indoles to α-silylated N-alkylated indoles.
Scheme 36: Conversion of β-amidoacrylates to α-aminosilanes.
Scheme 37: Conversion of α,β-unsaturated ketones to enantioenriched β-silylated ketones, nitriles, and nitro d...
Scheme 38: Regio-divergent silacarboxylation of allenes.
Scheme 39: Silylation of diazocarbonyl compounds, (A) asymmetric and (B) racemic.
Scheme 40: Enantioselective hydrosilylation of alkenes.
Scheme 41: Conversion of 3-acylindoles to indolino-silanes.
Scheme 42: Proposed mechanism for the silylation of 3-acylindoles.
Scheme 43: Silyation of N-chlorosulfonamides.
Scheme 44: Conversion of acyl silanes to α-silyl alcohols.
Scheme 45: Conversion of N-tosylaziridines to β-silylated N-tosylamines.
Scheme 46: Conversion of N-tosylaziridines to silylated N-tosylamines.
Scheme 47: Conversion of 3,3-disubstituted cyclopropenes to silylated cyclopropanes.
Scheme 48: Conversion of conjugated enynes to 1,3-bis(silyl)propenes.
Scheme 49: Proposed sequence for the Cu-catalyzed borylation of substituted alkenes.
Scheme 50: Cu-catalyzed synthesis of nonracemic allylic boronates.
Scheme 51: Cu–NHC catalyzed synthesis of α-substituted allylboronates.
Scheme 52: Synthesis of α-chiral (γ-alkoxyallyl)boronates.
Scheme 53: Cu-mediated formation of nonracemic cis- or trans- 2-substituted cyclopropylboronates.
Scheme 54: Cu-catalyzed synthesis of γ,γ-gem-difluoroallylboronates.
Scheme 55: Cu-catalyzed hydrofunctionalization of internal alkenes and vinylarenes.
Scheme 56: Cu-catalyzed Markovnikov and anti-Markovnikov borylation of alkenes.
Scheme 57: Cu-catalyzed borylation/ortho-cyanation/Cope rearrangement.
Scheme 58: Borylfluoromethylation of alkenes.
Scheme 59: Cu-catalyzed synthesis of tertiary nonracemic alcohols.
Scheme 60: Synthesis of densely functionalized and synthetically versatile 1,2- or 4,3-borocyanated 1,3-butadi...
Scheme 61: Cu-catalyzed trifunctionalization of allenes.
Scheme 62: Cu-catalyzed selective arylborylation of arenes.
Scheme 63: Asymmetric borylative coupling between styrenes and imines.
Scheme 64: Regio-divergent aminoboration of unactivated terminal alkenes.
Scheme 65: Cu-catalyzed 1,4-borylation of α,β-unsaturated ketones.
Scheme 66: Cu-catalyzed protodeboronation of α,β-unsaturated ketones.
Scheme 67: Cu-catalyzed β-borylation of α,β-unsaturated imines.
Scheme 68: Cu-catalyzed synthesis of β-trifluoroborato carbonyl compounds.
Scheme 69: Asymmetric 1,4-borylation of α,β-unsaturated carbonyl compounds.
Scheme 70: Cu-catalyzed ACB and ACA reactions of α,β-unsaturated 2-acyl-N-methylimidazoles.
Scheme 71: Cu-catalyzed diborylation of aldehydes.
Scheme 72: Umpolung pathway for chiral, nonracemic tertiary alcohol synthesis (top) and proposed mechanism for...
Scheme 73: Cu-catalyzed synthesis of α-hydroxyboronates.
Scheme 74: Cu-catalyzed borylation of ketones.
Scheme 75: Cu-catalyzed borylation of unactivated alkyl halides.
Scheme 76: Cu-catalyzed borylation of allylic difluorides.
Scheme 77: Cu-catalyzed borylation of cyclic and acyclic alkyl halides.
Scheme 78: Cu-catalyzed borylation of unactivated alkyl chlorides and bromides.
Scheme 79: Cu-catalyzed decarboxylative borylation of carboxylic acids.
Scheme 80: Cu-catalyzed borylation of benzylic, allylic, and propargylic alcohols.
Combination of multicomponent KA2 and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones
- Riccardo Innocenti,
- Elena Lenci,
- Gloria Menchi and
- Andrea Trabocchi
Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23
- generate the maximum diversity and complexity from simple starting materials applying divergent synthetic strategies, such as the use of complexity-generating reactions and the build/couple/pair approach [17][18]. The application of multicomponent approaches has proven to be very useful as starting points
Graphical Abstract
Figure 1: Chemical structure of representative approved drugs containing a spirocyclic moiety.
Scheme 1: Synthetic strategies for accessing pyrrolocyclopentenone derivatives, including the novel couple/pa...
Scheme 2: Couple/pair approach using combined KA2 and Pauson–Khand multicomponent reactions.
Scheme 3: Follow-up chemistry on compound 5 taking advantage of the enone chemistry. Reaction conditions. (i)...
Figure 2: Top: Selected NOE contacts from NOESY 1D spectra of compound 36; bottom: low energy conformer of 36...
Figure 3: PCA plot resulting from the correlation between PC1 vs PC2, showing the positioning in the chemical...
Figure 4: PMI plot showing the skeletal diversity of compounds 3–39 (blue diamonds) with respect to the refer...
Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction
- Renata Kaczmarek,
- Dariusz Korczyński,
- James R. Green and
- Roman Dembinski
Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1
- confirmed that the Nicholas reaction can be carried out in a nucleoside presence, leading to a divergent synthesis of novel metallo-nucleosides enriched with alkene, arene, arylketo, and heterocyclic functions, in the deoxy and ribo series. Keywords: alkynes; 5-alkynyluridines; C–C-bond formation; dicobalt
- ]. Consequently, we aimed to develop methods that would synthetically extend the design of the metallo-nucleosides by introducing functionalized ligands in divergent synthesis. We decided to pursue the Nicholas reaction in the presence of the labile nucleoside unit, further modifying the already available
- -nucleosides, preserving the dicobalt hexacarbonyl unit. This methodology allows for access in a divergent fashion to a variety of modified nucleosides with potential biological activity, and was shown to be viable for both 2'-deoxy- and regular uridines. Experimental General and instrumentation. All NMR
Graphical Abstract
Scheme 1: Preparation of (2'-deoxy)-5-alkynyluridines 2 and 3, their dicobalt hexacarbonyl derivatives 4 and 5...
Figure 1: Structures of nucleosides 6 and 7, products of the Nicholas reaction.
