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Search for "nucleophilic addition" in Full Text gives 275 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process
- Muthumani Muthu,
- Rakkappan Vishnu Priya,
- Abdulrahman I. Almansour,
- Raju Suresh Kumar and
- Raju Ranjith Kumar
Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269
- condensation–nucleophilic addition to carbonyl–Michael addition–N-cyclization–elimination–air oxidation sequence to afford structurally intriguing indole–cycloalkyl[b]pyridine-3-carbonitrile hybrid heterocycles in excellent yields. Keywords: cycloalkyl[b]pyridine-3-carbonitrile; cyclododecanone; 3-(1H-indol-3
- –cycloalkyl[b]pyridine-3-carbonitrile hybrid heterocycles have been achieved through a facile one-pot four-component strategy. This reaction occurred through a six-step tandem Hantzsch-like process involving Knoevenagel–Michael–nucleophilic addition–intramolecular cyclization–elimination–oxidative
Graphical Abstract
Figure 1: Examples of biologically important cycloalkyl-fused pyridines.
Scheme 1: Synthesis of 3-oxopropanenitriles 3.
Scheme 2: Proposed mechanism for the formation of 7f.
Scheme 3: Synthesis of indole–cyclododeca[b]pyridine-3-carbonitriles 7 and 14.
Figure 2: Axial chirality due to restricted C–C bond rotation (representative cases).
Figure 3: ORTEP diagram of 12r.
Scheme 4: Synthesis of indole–cycloalkyl[b]pyridine-3-carbonitrile hybrids 15–18.
Figure 4: ORTEP diagram of 16f.
Hydroarylations by cobalt-catalyzed C–H activation
- Rajagopal Santhoshkumar and
- Chien-Hong Cheng
Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202
- undergoes oxidative addition with arylpyridine to generate I1. Then, elimination of neopentane (R–H) by reductive elimination gives cobaltacycle I2. Nucleophilic addition of I2 to imines, followed by transmetallation with a Grignard reagent and protonation provide the desired hydroarylation product 57. In
- addition to imines, aziridines were also amenable to the cobalt-catalyzed hydroarylation reaction (Scheme 36) [96]. Treatment of 2-phenylpyridines 3 with varies aryl-substituted aziridines gave 1,1-diarylethane derivatives 58 in a highly regioselective manner. It is noteworthy that nucleophilic addition
Graphical Abstract
Scheme 1: Cobalt-catalyzed C–H carbonylation.
Scheme 2: Hydroarylation by C–H activation.
Scheme 3: Pathways for cobalt-catalyzed hydroarylations.
Scheme 4: Co-catalyzed hydroarylation of alkynes with azobenzenes.
Scheme 5: Co-catalyzed hydroarylation of alkynes with 2-arylpyridines.
Scheme 6: Co-catalyzed addition of azoles to alkynes.
Scheme 7: Co-catalyzed addition of indoles to alkynes.
Scheme 8: Co-catalyzed hydroarylation of alkynes with imines.
Scheme 9: A plausible pathway for Co-catalyzed hydroarylation of alkynes.
Scheme 10: Co-catalyzed anti-selective C–H addition to alkynes.
Scheme 11: Co(III)-catalyzed hydroarylation of alkynes with indoles.
Scheme 12: Co(III)-catalyzed branch-selective hydroarylation of alkynes.
Scheme 13: Co(III)-catalyzed hydroarylation of terminal alkynes with arenes.
Scheme 14: Co(III)-catalyzed hydroarylation of alkynes with amides.
Scheme 15: Co(III)-catalyzed C–H alkenylation of arenes.
Scheme 16: Co-catalyzed alkylation of substituted benzamides with alkenes.
Scheme 17: Co-catalyzed switchable hydroarylation of styrenes with 2-aryl pyridines.
Scheme 18: Co-catalyzed linear-selective hydroarylation of alkenes with imines.
Scheme 19: Co-catalyzed linearly-selective hydroarylation of alkenes with N–H imines.
Scheme 20: Co-catalyzed branched-selective hydroarylation of alkenes with imines.
Scheme 21: Mechanism of Co-catalyzed hydroarylation of alkenes.
Scheme 22: Co-catalyzed intramolecular hydroarylation of indoles.
Scheme 23: Co-catalyzed asymmetric hydroarylation of alkenes with indoles.
Scheme 24: Co-catalyzed hydroarylation of alkenes with heteroarenes.
Scheme 25: Co(III)-catalyzed hydroarylation of activated alkenes with 2-phenyl pyridines.
Scheme 26: Co(III)-catalyzed C–H alkylation of arenes.
Scheme 27: Co(III)-catalyzed C2-alkylation of indoles.
Scheme 28: Co(III)-catalyzed switchable hydroarylation of alkyl alkenes with indoles.
Scheme 29: Co(III)-catalyzed C2-allylation of indoles.
Scheme 30: Co(III)-catalyzed ortho C–H alkylation of arenes with maleimides.
Scheme 31: Co(III)-catalyzed hydroarylation of maleimides with arenes.
Scheme 32: Co(III)-catalyzed hydroarylation of allenes with arenes.
Scheme 33: Co-catalyzed hydroarylative cyclization of enynes with carbonyl compounds.
Scheme 34: Mechanism for the Co-catalyzed hydroarylative cyclization of enynes with carbonyl compounds.
Scheme 35: Co-catalyzed addition of 2-arylpyridines to aromatic aldimines.
Scheme 36: Co-catalyzed addition of 2-arylpyridines to aziridines.
Scheme 37: Co(III)-catalyzed hydroarylation of imines with arenes.
Scheme 38: Co(III)-catalyzed addition of arenes to ketenimines.
Scheme 39: Co(III)-catalyzed three-component coupling.
Scheme 40: Co(III)-catalyzed hydroarylation of aldehydes.
Scheme 41: Co(III)-catalyzed addition of arenes to isocyanates.
Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases
- Maroš Bella,
- Sergej Šesták,
- Ján Moncoľ,
- Miroslav Koóš and
- Monika Poláková
Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189
- be achieved via nucleophilic addition of MeMgBr to an aldehyde obtained by the oxidation of alcohol 7. Despite this fact, we did not manage the preparation of the aldehyde by the oxidation of alcohol 7 probably due to its instability [33]. However, similar aldehyde 17 bearing a Cbz protecting group
Graphical Abstract
Figure 1: Structures of GMIIb inhibitors.
Scheme 1: Synthesis of pyrrolidines 2a and 3a.
Scheme 2: Synthesis of pyrrolidines 2b,c and 3b,c.
Scheme 3: Synthesis of pyrrolidines 4.
Scheme 4: Synthesis of pyrrolidines 5.
Figure 2: Molecular structure (OLEX2 drawing with adjacent ChemDraw image) of compound 20. Atomic displacemen...
Studies towards the synthesis of hyperireflexolide A
- G. Hari Mangeswara Rao
Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185
- of the proposed synthetic sequence. Future studies will include the stereoselective epoxidation of 11 followed by opening of the epoxide and lactonization or 1,4-nucleophilic addition to the α,β-unsaturated ketone 11 followed by epoxidation of the resulted enolate with subsequent lactonization to
Graphical Abstract
Figure 1: Hyperireflexolide A.
Scheme 1: Retrosynthetic strategy.
Scheme 2: Hydrolysis of dimethyl ketal 5.
Scheme 3: Alkylation of γ-lactone-fused β-ketoester 6.
Scheme 4: Synthesis of α,β-unsaturated ketone 11.
Functionalization of graphene: does the organic chemistry matter?
- Artur Kasprzak,
- Agnieszka Zuchowska and
- Magdalena Poplawska
Beilstein J. Org. Chem. 2018, 14, 2018–2026, doi:10.3762/bjoc.14.177
- ], the approach to the synthesis of the material has not been given in some cases; in other words, the researchers have not always discussed whether the process is based on the non-covalent adsorption of the reactant or whether it follows the nucleophilic addition to GO’s epoxides. On the basis of the
Graphical Abstract
Figure 1: Partial structure [7,8] of the (a) graphene oxide (GO) and (b) reduced graphene oxide (RGO).
Figure 2: Mechanism of the amidation/esterification-type reactions with the GO/RGO using carbodiimide and N-h...
Figure 3: Mechanism of the Steglich esterification with the GO/RGO: (a) acid–base reaction of the carboxyl gr...
Figure 4: Mechanism of the epoxide ring opening reaction with the GO/RGO.
Figure 5: Generation of the free amine (nucleophile) from the corresponding amine hydrohalide using an acid–b...
Figure 6: Mechanism of amidation/esterification-type reactions with the GO/RGO using 1,1’-carbonyldiimidazole...
Figure 7: Mechanism of the covalent functionalization of graphene-family material applying diazonium salts ch...
Cobalt-catalyzed nucleophilic addition of the allylic C(sp3)–H bond of simple alkenes to ketones
- Tsuyoshi Mita,
- Masashi Uchiyama,
- Kenichi Michigami and
- Yoshihiro Sato
Beilstein J. Org. Chem. 2018, 14, 2012–2017, doi:10.3762/bjoc.14.176
- regeneration of I. Alkoxide VI is converted to homoallylic alcohol 3aa by usual work-up. Conclusion In conclusion, we have successfully developed a cobalt-catalyzed nucleophilic addition of the C(sp3)–H bond of simple alkenes to ketones. This novel transformation could realize perfect branch selectivity for
Graphical Abstract
Figure 1: Precedent examples of catalytic allylic C(sp3)–H additions to carbonyl electrophiles.
Figure 2: Substrate scope for acetophenone derivatives. aPreparative scale synthesis using 1 mmol of 2a.
Figure 3: Substrate scope for α-olefins.
Figure 4: A possible catalytic cycle.
β-Hydroxy sulfides and their syntheses
- Mokgethwa B. Marakalala,
- Edwin M. Mmutlane and
- Henok H. Kinfe
Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143
- group from succinimide 103 to the chiral pre-catalyst 104 to generate the active species 110 (Scheme 40). Reaction of the alkene with the active species 110 results to the formation of the thiiranium intermediate 111, which then undergoes a stereoselective nucleophilic addition to provide the thioethers
Graphical Abstract
Figure 1: Some sulfur-containing natural products.
Figure 2: Some natural products incorporating β-hydroxy sulfide moieties.
Figure 3: Some synthetic β-hydroxy sulfides of clinical value.
Scheme 1: Alumina-mediated synthesis of β-hydroxy sulfides, ethers, amines and selenides from epoxides.
Scheme 2: β-Hydroxy sulfide syntheses by ring opening of epoxides under different Lewis and Brønsted acid and...
Scheme 3: n-Bu3P-catalyzed thiolysis of epoxides and aziridines to provide the corresponding β-hydroxy and β-...
Scheme 4: Zinc(II) chloride-mediated thiolysis of epoxides.
Scheme 5: Thiolysis of epoxides and one-pot oxidation to β-hydroxy sulfoxides under microwave irradiation.
Scheme 6: Gallium triflate-catalyzed ring opening of epoxides and one-pot oxidation.
Scheme 7: Thiolysis of epoxides and one-pot oxidation to β-hydroxy sulfoxides using Ga(OTf)3 as a catalyst.
Scheme 8: Ring opening of epoxide using ionic liquids under solvent-free conditions.
Scheme 9: N-Bromosuccinimide-catalyzed ring opening of epoxides.
Scheme 10: LiNTf2-mediated epoxide opening by thiophenol.
Scheme 11: Asymmetric ring-opening of cyclohexene oxide with various thiols catalyzed by zinc L-tartrate.
Scheme 12: Catalytic asymmetric ring opening of symmetrical epoxides with t-BuSH catalyzed by (R)-GaLB (43) wi...
Scheme 13: Asymmetric ring opening of meso-epoxides by p-xylenedithiol catalyzed by a (S,S)-(salen)Cr complex.
Scheme 14: Desymmetrization of meso-epoxide with thiophenol derivatives.
Scheme 15: Enantioselective ring-opening reaction of meso-epoxides with ArSH catalyzed by a C2-symmetric chira...
Scheme 16: Enantioselective ring-opening reaction of stilbene oxides with ArSH catalyzed by a C2-symmetric chi...
Scheme 17: Asymmetric desymmetrization of meso-epoxides using BINOL-based Brønsted acid catalysts.
Scheme 18: Lithium-BINOL-phosphate-catalyzed desymmetrization of meso-epoxides with aromatic thiols.
Scheme 19: Ring-opening reactions of cyclohexene oxide with thiols by using CPs 1-Eu and 2-Tb.
Scheme 20: CBS-oxazaborolidine-catalyzed borane reduction of β-keto sulfides.
Scheme 21: Preparation of β-hydroxy sulfides via connectivity.
Scheme 22: Baker’s yeast-catalyzed reduction of sulfenylated β-ketoesters.
Scheme 23: Sodium-mediated ring opening of epoxides.
Scheme 24: Disulfide bond cleavage-epoxide opening assisted by tetrathiomolybdate.
Scheme 25: Proposed reaction mechanism of disulfide bond cleavage-epoxide opening assisted by tetrathiomolybda...
Scheme 26: Cyclodextrin-catalyzed difunctionalization of alkenes.
Scheme 27: Zinc-catalyzed synthesis of β-hydroxy sulfides from disulfides and alkenes.
Scheme 28: tert-Butyl hydroperoxide-catalyzed hydroxysulfurization of alkenes.
Scheme 29: Proposed mechanism of the radical hydroxysulfurization.
Scheme 30: Rongalite-mediated synthesis of β-hydroxy sulfides from styrenes and disulfides.
Scheme 31: Proposed mechanism of Rongalite-mediated synthesis of β-hydroxy sulfides from styrenes and disulfid...
Scheme 32: Copper(II)-catalyzed synthesis of β-hydroxy sulfides 15e,f from alkenes and basic disulfides.
Scheme 33: CuI-catalyzed acetoxysulfenylation of alkenes.
Scheme 34: CuI-catalyzed acetoxysulfenylation reaction mechanism.
Scheme 35: One-pot oxidative 1,2-acetoxysulfenylation of Baylis–Hillman products.
Scheme 36: Proposed mechanism for the oxidative 1,2-acetoxysulfination of Baylis–Hillman products.
Scheme 37: 1,2-Acetoxysulfenylation of alkenes using DIB/KI.
Scheme 38: Proposed reaction mechanism of the diacetoxyiodobenzene (DIB) and KI-mediated 1,2-acetoxysulfenylat...
Scheme 39: Catalytic asymmetric thiofunctionalization of unactivated alkenes.
Scheme 40: Proposed catalytic cycle for asymmetric sulfenofunctionalization.
Scheme 41: Synthesis of thiosugars using intramolecular thiol-ene reaction.
Scheme 42: Synthesis of leukotriene C-1 by Corey et al.: (a) N-(trifluoroacetyl)glutathione dimethyl ester (3 ...
Scheme 43: Synthesis of pteriatoxins with epoxide thiolysis to attain β-hydroxy sulfides. Reagents: (a) (1) K2...
Scheme 44: Synthesis of peptides containing a β-hydroxy sulfide moiety.
Scheme 45: Synthesis of diltiazem (12) using biocatalytic resolution of an epoxide followed by thiolysis.
Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis
- Gwendal Grelier,
- Benjamin Darses and
- Philippe Dauban
Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128
- transformations involving stoichiometric amounts of λ3- or λ5-iodanes, thus, has been improved by designing tandem reactions that allows for incorporating the aryl motif into the products through a subsequent one-pot nucleophilic addition or catalytic coupling reaction. This review summarizes the main
- to the triple bond of 22 to give the intermediate 26, followed by the reductive elimination of the trivalent iodine motif to afford the palladium-vinylidene 27. This would undergo a nucleophilic addition of the imine and a subsequent proto-demetallation to give enamine 29. A series of rearrangements
Graphical Abstract
Scheme 1: Strategies to address the issue of sustainability with polyvalent organoiodine reagents.
Scheme 2: Functionalization of ketones and alkenes with IBX.
Scheme 3: Functionalization of pyrroles with DMP.
Scheme 4: Catalytic benzoyloxy-trifluoromethylation reported by Szabó.
Scheme 5: Catalytic benzoyloxy-trifluoromethylation reported by Mideoka.
Scheme 6: Catalytic 1,4-benzoyloxy-trifluoromethylation of dienes.
Scheme 7: Catalytic benzoyloxy-trifluoromethylation of allylamines.
Scheme 8: Catalytic benzoyloxy-trifluoromethylation of enynes.
Scheme 9: Catalytic benzoyloxy-trifluoromethylation of allenes.
Scheme 10: Alkynylation of N-(aryl)imines with EBX for the formation of furans.
Scheme 11: Catalytic benzoyloxy-alkynylation of diazo compounds.
Scheme 12: Catalytic asymmetric benzoyloxy-alkynylation of diazo compounds.
Scheme 13: Catalytic 1,2-benzoyloxy-azidation of alkenes.
Scheme 14: Catalytic 1,2-benzoyloxy-azidation of enamides.
Scheme 15: Catalytic 1,2-benzoyloxy-iodination of alkenes.
Scheme 16: Seminal study with cyclic diaryl-λ3-iodane.
Scheme 17: Synthesis of alkylidenefluorenes from cyclic diaryl-λ3-iodanes.
Scheme 18: Synthesis of alkyne-substituted alkylidenefluorenes.
Scheme 19: Synthesis of phenanthrenes from cyclic diaryl-λ3-iodanes.
Scheme 20: Synthesis of dibenzocarbazoles from cyclic diaryl-λ3-iodanes.
Scheme 21: Synthesis of triazolophenantridines from cyclic diaryl-λ3-iodanes.
Scheme 22: Synthesis of functionalized benzoxazoles from cyclic diaryl-λ3-iodanes.
Scheme 23: Sequential difunctionalization of cyclic diaryl-λ3-iodanes.
Scheme 24: Double Suzuki–Miyaura coupling reaction of cyclic diaryl-λ3-iodanes.
Scheme 25: Synthesis of a δ-carboline from cyclic diaryl-λ3-iodane.
Scheme 26: Synthesis of N-(aryl)carbazoles from cyclic diaryl-λ3-iodanes.
Scheme 27: Synthesis of carbazoles from cyclic diaryl-λ3-iodanes.
Scheme 28: Synthesis of carbazoles and acridines from cyclic diaryl-λ3-iodanes.
Scheme 29: Synthesis of dibenzothiophenes from cyclic diaryl-λ3-iodanes.
Scheme 30: Synthesis of various sulfur heterocycles from cyclic diaryl-λ3-iodanes.
Scheme 31: Synthesis of dibenzothioheterocycles from cyclic diaryl-λ3-iodanes.
Scheme 32: Synthesis of dibenzosulfides and dibenzoselenides from cyclic diaryl-λ3-iodanes.
Scheme 33: Synthesis of dibenzosulfones from cyclic diaryl-λ3-iodanes.
Scheme 34: Seminal study with linear diaryl-λ3-iodanes.
Scheme 35: N-Arylation of benzotriazole with symmetrical diaryl-λ3-iodanes.
Scheme 36: Tandem catalytic C–H/N–H arylation of indoles with diaryl-λ3-iodanes.
Scheme 37: Tandem N-arylation/C(sp2)–H arylation with diaryl-λ3-iodanes.
Scheme 38: Catalytic intermolecular diarylation of anilines with diaryl-λ3-iodanes.
Scheme 39: Catalytic synthesis of diarylsulfides with diaryl-λ3-iodanes.
Scheme 40: α-Arylation of enolates using [bis(trifluoroacetoxy)iodo]arenes.
Scheme 41: Mechanism of the α-arylation using [bis(trifluoroacetoxy)iodo]arene.
Scheme 42: Catalytic nitrene additions mediated by [bis(acyloxy)iodo]arenes.
Scheme 43: Tandem of C(sp3)–H amination/sila-Sonogashira–Hagihara coupling.
Scheme 44: Tandem reaction using a λ3-iodane as an oxidant, a substrate and a coupling partner.
Scheme 45: Synthesis of 1,2-diarylated acrylamidines with ArI(OAc)2.
Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines
- Hélène Pellissier
Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114
- imines published since the beginning of 2015. Keywords: asymmetric synthesis; chiral 3-amino-2-oxindoles; chirality; isatin imines; nucleophilic addition; Introduction Chiral oxindoles represent an important class of products widely present in nature and exhibiting many biological activities. Among
Graphical Abstract
Scheme 1: Mannich reaction of N-Boc-isatin imines with ethyl nitroacetate (2) catalyzed by a cinchona alkaloi...
Scheme 2: Mannich reaction of N-Boc-isatin imines with 1,3-dicarbonyl compounds catalyzed by a cinchona alkal...
Scheme 3: Mannich reaction of N-alkoxycarbonylisatin imines with acetylacetone catalyzed by a cinchona alkalo...
Scheme 4: Mannich reaction of isatin-derived benzhydrylketimines with trimethylsiloxyfuran catalyzed by a pho...
Scheme 5: Mannich reaction of N-Boc-isatin imines with acetaldehyde catalyzed by a primary amine.
Scheme 6: Mannich reaction of N-Cbz-isatin imines with aldehydes catalyzed by L-diphenylprolinol trimethylsil...
Scheme 7: Addition of dimedone-derived enaminones to N-Boc-isatin imines catalyzed by a phosphoric acid.
Scheme 8: Addition of hydroxyfuran-2-one-derived enaminones to N-Boc-isatin imines catalyzed by a phosphoric ...
Scheme 9: Zinc-catalyzed Mannich reaction of N-Boc-isatin imines with silyl ketene imines.
Scheme 10: Tin-catalyzed Mannich reaction of N-arylisatin imines with an alkenyl trichloroacetate.
Scheme 11: Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with acrolein catalyzed by β-isocupreidin...
Scheme 12: Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with acrolein (35) catalyzed by α-isocupr...
Scheme 13: Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with maleimides catalyzed by β-isocupreid...
Scheme 14: Aza-Morita–Baylis–Hillman reaction of N-Boc-isatin imines with nitroolefins catalyzed by a cinchona...
Scheme 15: Friedel–Crafts reactions of N-Boc-isatin imines with 1 and 2-naphthols catalyzed by a cinchona alka...
Scheme 16: Friedel–Crafts reactions of N-alkoxycarbonyl-isatin imines with 1 and 2-naphthols catalyzed by a ci...
Scheme 17: Friedel–Crafts reaction of N-Boc-isatin imines with 6-hydroxyquinolines catalyzed by a cinchona alk...
Scheme 18: Aza-Henry reaction of N-Boc-isatin imines with nitromethane catalyzed by a bifunctional guanidine.
Scheme 19: Domino addition/cyclization reaction of N-Boc-isatin imines with 1,4-dithiane-2,5-diol (53) catalyz...
Scheme 20: Nickel-catalyzed additions of methanol and cumene hydroperoxide to N-Boc-isatin imines.
Scheme 21: Palladium-catalyzed addition of arylboronic acids to N-tert-butylsulfonylisatin imines.
A survey of chiral hypervalent iodine reagents in asymmetric synthesis
- Soumen Ghosh,
- Suman Pradhan and
- Indranil Chatterjee
Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107
- aminoarylation of alkenes 53 to produce 54 (Scheme 11). The presence of a silyloxy group is essential to achieve high enantioselectivity in case of the oxyarylation [49]. The Lewis acid activates the hypervalent chiral iodine reagent and then adds to the alkene system. The nucleophilic addition of the internal
- oxy/amino group followed by the nucleophilic addition of the aryl group delivers the desired products 54. The key to success also lies on the enantiotopic face discrimination of the alkene by the lactate-based chiral iodine reagent. This difunctionalization strategy was further showcased by Muñiz et
Graphical Abstract
Scheme 1: An overview of different chiral iodine reagents or precursors thereof.
Scheme 2: Asymmetric oxidation of sulfides by chiral hypervalent iodine reagents.
Scheme 3: Oxidative dearomatization of naphthol derivatives by Kita et al.
Scheme 4: [4 + 2] Diels–Alder dimerization reported by Birman et al.
Scheme 5: m-CPBA guided catalytic oxidative naphthol dearomatization.
Scheme 6: Oxidative dearomatization of phenolic derivatives by Ishihara et al.
Scheme 7: Oxidative spirocyclization applying precatalyst 11 developed by Ciufolini et al.
Scheme 8: Asymmetric hydroxylative dearomatization.
Scheme 9: Enantioselective oxylactonization reported by Fujita et al.
Scheme 10: Dioxytosylation of styrene (47) by Wirth et al.
Scheme 11: Oxyarylation and aminoarylation of alkenes.
Scheme 12: Asymmetric diamination of alkenes.
Scheme 13: Stereoselective oxyamination of alkenes reported by Wirth et al.
Scheme 14: Enantioselective and regioselective aminofluorination by Nevado et al.
Scheme 15: Fluorinated difunctionalization reported by Jacobsen et al.
Scheme 16: Aryl rearrangement reported by Wirth et al.
Scheme 17: α-Arylation of β-ketoesters.
Scheme 18: Asymmetric α-oxytosylation of carbonyls.
Scheme 19: Asymmetric α-oxygenation and α-amination of carbonyls reported by Wirth et al.
Scheme 20: Asymmetric α-functionalization of ketophenols using chiral quaternary ammonium (hypo)iodite salt re...
Scheme 21: Oxidative Intramolecular coupling by Gong et al.
Scheme 22: α-Sulfonyl and α-phosphoryl oxylation of ketones reported by Masson et al.
Scheme 23: α-Fluorination of β-keto esters.
Scheme 24: Alkynylation of β-ketoesters and amides catalyzed by phase-transfer catalyst.
Scheme 25: Alkynylation of β-ketoesters and dearomative alkynylation of phenols.
Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations
- Koichi Mitsudo,
- Junya Yamamoto,
- Tomoya Akagi,
- Atsuhiro Yamashita,
- Masahiro Haisa,
- Kazuki Yoshioka,
- Hiroki Mandai,
- Koji Ueoka,
- Christian Hempel,
- Jun-ichi Yoshida and
- Seiji Suga
Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100
Graphical Abstract
Scheme 1: Generation and reaction of cationic species generated by “indirect cation pool” methods.
Figure 1: (a) 1H NMR of N-acyliminium ion C1 in CD2Cl2 at −80 °C (600 MHz). (b) Preferred conformation of C1.
Figure 2: (a) 1H NMR spectrum of C3 in CD2Cl2 at −60 °C (400 MHz). (b) Preferred conformation of C3.
Figure 3: (a) 1H NMR spectrum of C5 in CD2Cl2 at −60 °C (400 MHz). (b) Preferred conformation of C5.
Figure 4: Summary of the conformations of N-acyliminium ions C1–C6.
Figure 5: Stevens’ hypothesis on the tendency of the addition of nucleophiles to N-acyliminium ions. The subs...
Figure 6: A plausible mechanism of the observed diastereoselective reaction of the N-acyliminium ions.
Figure 7: Comparison of ΔG for the pseudo-equatorial and pseudo-axial conformations of C1–C6 at the B3LYP/6-3...
One hundred years of benzotropone chemistry
- Arif Dastan,
- Haydar Kilic and
- Nurullah Saracoglu
Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98
- as a fairly air-stable red-brown solid. b. Nucleophilic addition to 4,5-benzotropone (11): Ried’s group realized the reaction of 4,5-benzotropone (11) and its derivatives with lithium acetylide as a nucleophile between −50 and −32 °C [130]. While the possible 1,4-conjugate addition product 149 was
Graphical Abstract
Scheme 1: Tropone (1), tropolone (2) and their resonance structures.
Figure 1: Natural products containing a tropone nucleus.
Figure 2: Possible isomers 11–13 of benzotropone.
Scheme 2: Synthesis of benzotropones 11 and 12.
Scheme 3: Oxidation products of benzotropylium fluoroborate (16).
Scheme 4: Oxidation of 7-bromo-5H-benzo[7]annulene (22).
Scheme 5: Synthesis of 4,5-benzotropone (11) using o-phthalaldehyde (27).
Scheme 6: Synthesis of 4,5-benzotropone (11) starting from oxobenzonorbornadiene 31.
Scheme 7: Acid-catalyzed cleavage of oxo-bridge of 34.
Scheme 8: Synthesis of 4,5-benzotropone (11) from o-xylylene dibromide (38).
Scheme 9: Synthesis of 4,5-benzotropone (11) via the carbene adduct 41.
Scheme 10: Heck coupling strategy for the synthesis of 11.
Scheme 11: Synthesis of benzofulvalenes via carbonyl group of 4,5-benzotropone (11).
Figure 3: Some cycloheptatrienylium cations.
Scheme 12: Synthesis of condensation product 63 and its subsequent oxidative cyclization products.
Figure 4: A novel series of benzo[7]annulenes prepared from 4,5-benzotropone (11).
Scheme 13: Preparation of substituted benzo[7]annulene 72 using the Mukaiyama-Michael reaction.
Figure 5: Possible benzo[7]annulenylidenes 73–75.
Scheme 14: Thermal and photochemical decomposition of 7-diazo-7H-benzo[7]annulene (76) and the trapping of int...
Scheme 15: Synthesis of benzoheptafulvalene 86.
Scheme 16: Synthesis of 7-(diphenylmethylene)-7H-benzo[7]annulene (89).
Scheme 17: Reaction of 4,5-benzotropone (11) with dimethyl diazomethane.
Scheme 18: Synthesis of dihydrobenzomethoxyazocine 103.
Scheme 19: Synthesis and reducibility of benzo-homo-2-methoxyazocines.
Scheme 20: Synthesis of 4,5-benzohomotropones 104 and 115 from 4,5-benzotropones 11 and 113.
Scheme 21: A catalytic deuterogenation of 4,5-benzotropone (11) and synthesis of 5-monosubstituted benzo[7]ann...
Scheme 22: Synthesis of methyl benzo[7]annulenes 131 and 132.
Scheme 23: Ambident reactivity of halobenzo[7]annulenylium cations 133a/b.
Scheme 24: Preparation of benzo[7]annulenylidene–iron complexes 147.
Scheme 25: Synthesis of 1-ethynylbenzotropone (150) and the etheric compound 152 from 4,5-benzotropone (11) wi...
Scheme 26: Thermal decomposition of 4,5-benzotropone (11).
Scheme 27: Reaction of 4,5-benzotropone (11) with 1,2-ethanediol and 1,2-ethanedithiol.
Scheme 28: Conversions of 1-benzosuberone (162) to 2,3-benzotropone (12).
Scheme 29: Synthesis strategies for 2,3-bezotropone (12) using 1-benzosuberones.
Scheme 30: Oxidation-based synthesis of 2,3-benzotropone (12) via 1-benzosuberone (162).
Scheme 31: Synthesis of 2,3-benzotropone (12) from α-tetralone (171) via ring-expansion.
Scheme 32: Preparation of 2,3-benzotropone (12) by using of benzotropolone 174.
Figure 6: Benzoheptafulvenes as condensation products of 2,3-benzotropone (12).
Scheme 33: Conversion of 2,3-benzotropone (12) to tosylhydrazone salt 182 and gem-dichloride 187.
Figure 7: Benzohomoazocines 191–193 and benzoazocines 194–197.
Scheme 34: From 2,3-benzotropone (12) to carbonium ions 198–201.
Scheme 35: Cycloaddition reactions of 2,3-benzotropone (12).
Scheme 36: Reaction of 2,3-benzotropone (12) with various reagents and compounds.
Figure 8: 3,4-Benzotropone (13) and its resonance structure.
Scheme 37: Synthesis of 6,7-benzobicyclo[3.2.0]hepta-3,6-dien-2-one (230).
Figure 9: Photolysis and thermolysis products of 230.
Figure 10: Benzotropolones and their tautomeric structures.
Scheme 38: Synthesis strategies of 4,5-benzotropolone (238).
Scheme 39: Synthesis protocol for 2-hydroxy-4,5-benzotropone (238) using oxazole-benzo[7]annulene 247.
Figure 11: Some quinoxaline and pyrazine derivatives 254–256 prepared from 4,5-benzotropolone (238).
Scheme 40: Nitration product of 4,5-benzotropolone (238) and its isomerization to 1-nitro-naphthoic acid (259)....
Scheme 41: Synthesis protocol for 6-hydroxy-2,3-benzotropone (239) from benzosuberone (162).
Scheme 42: Various reactions via 6-hydroxy-2,3-benzotropone (239).
Scheme 43: Photoreaction of 6-hydroxy-2,3-benzotropone (239).
Scheme 44: Synthesis of 7-hydroxy-2,3-benzotropone (241) from benzosuberone (162).
Scheme 45: Synthesis strategy for 7-hydroxy-2,3-benzotropone (241) from ketone 276.
Scheme 46: Synthesis of 7-hydroxy-2,3-benzotropone (241) from β-naphthoquinone (280).
Scheme 47: Synthesis of 7-hydroxy-2,3-benzotropone (241) from bicyclic endoperoxide 213.
Scheme 48: Synthesis of 7-hydroxy-2,3-benzotropone (241) by ring-closing metathesis.
Figure 12: Various monosubstitution products 289–291 of 7-hydroxy-2,3-benzotropone (241).
Scheme 49: Reaction of 7-hydroxy-2,3-benzotropone (241) with various reagents.
Scheme 50: Synthesis of 4-hydroxy-2,3-benzotropones 174 and 304 from diketones 300/301.
Scheme 51: Catalytic hydrogenation of diketones 300 and 174.
Scheme 52: Synthesis of halo-benzotropones from alkoxy-naphthalenes 306, 307 and 310.
Figure 13: Unexpected byproducts 313–315 during synthesis of chlorobenzotropone 309.
Figure 14: Some halobenzotropones and their cycloadducts.
Scheme 53: Multisep synthesis of 2-chlorobenzotropone 309.
Scheme 54: A multistep synthesis of 2-bromo-benzotropone 26.
Scheme 55: A multistep synthesis of bromo-2,3-benzotropones 311 and 316.
Scheme 56: Oxidation reactions of 8-bromo-5H-benzo[7]annulene (329) with some oxidants.
Scheme 57: Synthesis of 2-bromo-4,5-benzotropone (26).
Scheme 58: Synthesis of 6-chloro-2,3-benzotropone (335) using LiCl and proposed intermediate 336.
Scheme 59: Reaction of 7-bromo-2,3-benzotropone (316) with methylamine.
Scheme 60: Reactions of bromo-2,3-benzotropones 26 and 311 with dimethylamine.
Scheme 61: Reactions of bromobenzotropones 311 and 26 with NaOMe.
Scheme 62: Reactions of bromobenzotropones 26 and 312 with t-BuOK in the presence of DPIBF.
Scheme 63: Cobalt-catalyzed reductive cross-couplings of 7-bromo-2,3-benzotropone (316) with cyclic α-bromo en...
Figure 15: Cycloadduct 357 and its di-π-methane rearrangement product 358.
Scheme 64: Catalytic hydrogenation of 2-chloro-4,5-benzotropone (311).
Scheme 65: Synthesis of dibromo-benzotropones from benzotropones.
Scheme 66: Bromination/dehydrobromination of benzosuberone (162).
Scheme 67: Some transformations of isomeric dibromo-benzotropones 261A/B.
Scheme 68: Transformations of benzotropolone 239B to halobenzotropolones 369–371.
Figure 16: Bromobenzotropolones 372–376 and 290 prepared via bromination/dehydrobromination strategy.
Scheme 69: Synthesis of some halobenzotropolones 289, 377 and 378.
Figure 17: Bromo-chloro-derivatives 379–381 prepared via chlorination.
Scheme 70: Synthesis of 7-iodo-3,4-benzotropolone (382).
Scheme 71: Hydrogenation of bromobenzotropolones 369 and 370.
Scheme 72: Debromination reactions of mono- and dibromides 290 and 375.
Figure 18: Nitratation and oxidation products of some halobenzotropolenes.
Scheme 73: Azo-coupling reactions of some halobenzotropolones 294, 375 and 378.
Figure 19: Four possible isomers of dibenzotropones 396–399.
Figure 20: Resonance structures of tribenzotropone (400).
Scheme 74: Two synthetic pathways for tribenzotropone (400).
Scheme 75: Synthesis of tribenzotropone (400) from dibenzotropone 399.
Scheme 76: Synthesis of tribenzotropone (400) from 9,10-phenanthraquinone (406).
Scheme 77: Synthesis of tribenzotropone (400) from trifluoromethyl-substituted arene 411.
Figure 21: Dibenzosuberone (414).
Figure 22: Reduction products 415 and 416 of tribenzotropone (400).
Figure 23: Structures of tribenzotropone dimethyl ketal 417 and 4-phenylfluorenone (412) and proposed intermed...
Figure 24: Structures of benzylidene- and methylene-9H-tribenzo[a,c,e][7]annulenes 419 and 420 and chiral phos...
Figure 25: Structures of tetracyclic alcohol 422, p-quinone methide 423 and cation 424.
Figure 26: Structures of host molecules 425–427.
Scheme 78: Synthesis of non-helical overcrowded derivatives syn/anti-431.
Figure 27: Hexabenzooctalene 432.
Figure 28: Structures of possible eight isomers 433–440 of naphthotropone.
Scheme 79: Synthesis of naphthotropone 437 starting from 1-phenylcycloheptene (441).
Scheme 80: Synthesis of 10-hydroxy-11H-cyclohepta[a]naphthalen-11-one (448) from diester 445.
Scheme 81: Synthesis of naphthotropone 433.
Scheme 82: Synthesis of naphthotropones 433 and 434 via cycloaddition reaction.
Scheme 83: Synthesis of naphthotropone 434 starting from 452.
Figure 29: Structures of tricarbonyl(tropone)irons 458, and possible cycloadducts 459.
Scheme 84: Synthesis of naphthotropone 436.
Scheme 85: Synthesis of precursor 465 for naphthotropone 435.
Scheme 86: Generation of naphthotropone 435 from 465.
Figure 30: Structures of tropylium cations 469 and 470.
Figure 31: Structures of tropylium ions 471+.BF4−, 472+.BF4−, and 473+.BF4−.
Scheme 87: Synthesis of tropylium ions 471+.BF4− and 479+.ClO4−.
Scheme 88: Synthesis of 1- and 2-methylanthracene (481 and 482) via carbene–carbene rearrangement.
Figure 32: Trapping products 488–490.
Scheme 89: Generation and chemistry of a naphthoannelated cycloheptatrienylidene-cycloheptatetraene intermedia...
Scheme 90: Proposed intermediates and reaction pathways for adduct 498.
Scheme 91: Exited-state intramolecular proton transfer of 505.
Figure 33: Benzoditropones 506 and 507.
Scheme 92: Synthesis of benzoditropone 506e.
Scheme 93: Synthetic approaches for dibenzotropone 507 via tropone (1).
Scheme 94: Formation mechanisms of benzoditropone 507 and 516 via 515.
Scheme 95: Synthesis of benzoditropones 525 and 526 from pyromellitic dianhydride (527).
Figure 34: Possible three benzocyclobutatropones 534–536.
Scheme 96: Synthesis of benzocyclobutatropones 534 and 539.
Scheme 97: Synthesis attempts for benzocyclobutatropone 545.
Scheme 98: Generation and trapping of symmetric benzocyclobutatropone 536.
Scheme 99: Synthesis of chloro-benzocyclobutatropone 552 and proposed mechanism of fluorenone derivatives.
Scheme 100: Synthesis of tropolone analogue 559.
Scheme 101: Synthesis of tropolones 561 and 562.
Figure 35: o/p-Tropoquinone rings (563 and 564) and benzotropoquinones (565–567).
Scheme 102: Synthesis of benzotropoquinone 566.
Scheme 103: Synthesis of benzotropoquinone 567 via a Diels–Alder reaction.
Figure 36: Products 575–577 through 1,2,3-benzotropoquinone hydrate 569.
Scheme 104: Structures 578–582 prepared from tropoquinone 567.
Figure 37: Two possible structures 583 and 584 for dibenzotropoquinone, and precursor compound 585 for 583.
Scheme 105: Synthesis of saddle-shaped ketone 592 using dibenzotropoquinone 584.
Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides
- Kartik Temburnikar and
- Katherine L. Seley-Radtke
Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65
- that is also based on the nucleophilic substitution of ribonolactone. Review Nucleophilic addition to D-ribonolactone and its stereochemistry Two prominent methods of C-nucleoside syntheses involve either i) the linear construction of a (hetero)aryl moiety on a C1'-functionalized ribose or ii) coupling
Graphical Abstract
Figure 1: Structural components of nucleic acids. Shown is the monomeric building block of nucleic acids. Cha...
Figure 2: Formation of oxocarbenium ion during glycosidic bond cleavage in nucleosides [31]. The extent of leavin...
Figure 3: Structural modifications to nucleobase-sugar connectivity. The O–C–N bond between nucleobase and su...
Figure 4: Examples of natural and synthetic C-nucleosides. Pseudouridine and formcycin are among several natu...
Figure 5: Synthetic approaches to C-nucleosides. A. Two common strategies for C-nucleoside synthesis involve ...
Figure 6: Steroselective C-nucleoside synthesis using D-ribonolactone. A. Nucleophilic substitution of D-ribo...
Figure 7: Synthesis of C1'-substituted 4-aza-7,9-dideazaadenine C-nucleosides [63-65,69,70]. A. Reaction of D-ribonolacton...
Figure 8: Pyrrolo- and imidazo[2,1-f][1,2,4]triazine C-nucleosides. A series of sugar- and nucleobase-substit...
Figure 9: Synthesis of 1',2'-cyclopentyl C-nucleoside [73]. Functional groups at C1' and C2' were installed and e...
Figure 10: Anti-influenza C-nucleosides mimicking favipiravir riboside [74]. A. Structure of favipiravir and its r...
Figure 11: Alternative method for synthesis of 2'-substituted C-nucleosides [75]. A. Synthesis of C2'-substituted ...
Figure 12: Synthesis of carbocyclic C-nucleosides using cyclopentanone [53]. A. Nucleophlic substitution on cyclop...
Figure 13: Synthesis of carbocyclic C-nucleosides via Suzuki coupling [53]. A. Synthesis of OTf-cyclopentene that ...
Mannich base-connected syntheses mediated by ortho-quinone methides
- Petra Barta,
- Ferenc Fülöp and
- István Szatmári
Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43
- and the aldehyde yields a Schiff base and then the latter reacts with 2-naphthol in the second nucleophilic addition step. The other theory assumes the formation of an ortho-quinone methide (o-QM) intermediate by the reaction of 2-naphthol and benzaldehyde. Re-aromatization, the driving force of the
- transformation, takes place in the second step by the nucleophilic addition of the amine component. The class of o-QMs has recently been investigated from many aspects. They are known as short-lived species playing an important role as key intermediates in numerous synthetic pathways. Reviews have recently been
- the desired 1-amidoalkyl-2-naphthol derivatives. This second step can also be considered as a nucleophilic addition of the amide to the o-QM component. Various catalysts and conditions were used to optimize reaction conditions considering economical and environmental aspects. These include microwave
Graphical Abstract
Scheme 1: Formation of amidoalkylnaphthols 4 via o-QM intermediate 3.
Scheme 2: Asymmetric syntheses of triarylmethanes starting from diarylmethylamines.
Scheme 3: Proposed mechanism for the formation of 2,2-dialkyl-3-dialkylamino-2,3-dihydro-1H-naphtho[2,1-b]pyr...
Scheme 4: Cycloadditions of isoflavonoid-derived o-QMs and various dienophiles.
Scheme 5: [4 + 2] Cycloaddition reactions between aminonaphthols and cyclic amines.
Scheme 6: Brønsted acid-catalysed reaction between aza-o-QMs and 2- or 3-substituted indoles.
Scheme 7: Formation of 3-(α,α-diarylmethyl)indoles 52 in different synthetic pathways.
Scheme 8: Alkylation of o-QMs with N-, O- or S-nucleophiles.
Scheme 9: Formation of DNA linkers and o-QM mediated polymers.
Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu4NI
- Mi-Hai Luo,
- Yang-Ye Jiang,
- Kun Xu,
- Yong-Guo Liu,
- Bao-Guo Sun and
- Cheng-Chu Zeng
Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35
- homogeneous reaction with N-arylglycine esters, N-iodo intermediate 4 was generated. Eliminating a molecule of HI affords imine intermediate 5. In the presence of acetic acid, the protonated 5-H+ undergoes nucleophilic addition with C–H nucleophiles 2 to give the desired products 3. Conclusion In summary, an
Graphical Abstract
Scheme 1: Cross dehydrogenative coupling of N-arylglycine esters with C–H nucleophiles.
Scheme 2: Electrochemical CDC reaction of 2a and various N-arylglycine esters. Reaction conditions for the in...
Scheme 3: Scope of 2 using n-Bu4NI as mediator. Reaction conditions:1a (0.5 mmol), 2 (0.6 mmol), n-Bu4NI (30 ...
Scheme 4: Scaling up.
Scheme 5: Control experiments.
Scheme 6: A plausible mechanism for the electrocatalytic cross dehydrogenative coupling of N-arylglycine este...
Recent developments in the asymmetric Reformatsky-type reaction
- Hélène Pellissier
Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21
- nucleophilic addition of ethyl iodoacetate to the Si face of the cyclic imine 67 affording the final β-amino ester 68 and regenerating dimer M. In 2017, a related chiral ligand 69 employed at only 10–20 mol % of catalyst loading was reported by the same authors to be capable of catalyzing in combination with
Graphical Abstract
Scheme 1: Reformatsky-type reaction.
Scheme 2: First total synthesis of prunustatin A based on a Zn-mediated Reformatsky reaction [17].
Scheme 3: Synthesis of a γ-hydroxylysine derivative through a Zn-mediated nitrile Reformatsky-type reaction [18].
Scheme 4: Synthesis of apratoxin E and its C30 epimer through a Zn-mediated Reformatsky reaction. Fmoc = 9-fl...
Scheme 5: Synthesis of the eastern fragment of jatrophane diterpene Pl-3 through a SmI2-mediated Reformatsky ...
Scheme 6: First total synthesis of prebiscibactin through a SmI2-mediated Reformatsky reaction. Boc = tert-bu...
Scheme 7: Synthesis of prostaglandin E2 methyl ester through a SmI2-mediated Reformatsky reaction [23].
Scheme 8: Synthesis of the C1–C11 fragment of tedanolide C through a SnCl2-mediated Reformatsky reaction. PMB...
Scheme 9: Synthesis of β-trifluoromethyl β-(N-tert-butylsulfinyl)amino esters exhibiting a quaternary stereoc...
Scheme 10: Synthesis of α,α-difluoro-β-(N-tert-butylsulfinyl)amino esters through Zn(II)-mediated aza-Reformat...
Scheme 11: Synthesis of a common fragment to anti-apoptotic protein inhibitors through a Zn-mediated aza-Refor...
Scheme 12: Synthesis of α,α-difluoro-β-(N-tert-butylsulfinyl)amino ketones through a Zn-mediated aza-Reformats...
Scheme 13: Synthesis of (2-oxoindolin-3-yl)amino esters through a Zn-mediated aza-Reformatsky reaction [30].
Scheme 14: Synthesis of a precursor of sacubitril through a Zn-mediated aza-Reformatsky reaction [31].
Scheme 15: Synthesis of epothilone D through a Cr(II)-mediated Reformatsky reaction. TFA = trifluoroacetic aci...
Scheme 16: Synthesis of β-hydroxy-α-methyl-δ-trichloromethyl-δ-valerolactone through a Sm(II)- or Yb(II)-media...
Scheme 17: Synthesis of cebulactam A1 through a Sm(II)-mediated Reformatsky reaction. MOM = methoxymethyl [34].
Scheme 18: Synthesis of ansamacrolactams (+)-Q-1047H-A-A and (+)-Q-1047H-R-A through a Sm(II)-mediated Reforma...
Scheme 19: Reformatsky reaction of aldehydes with ethyl iodoacetate in the presence of a chiral 1,2-amino alco...
Scheme 20: Reformatsky reaction of aldehydes with ethyl bromoacetate in the presence of a chiral amide ligand [44]....
Scheme 21: Reformatsky reaction of cinnamaldehyde with ethyl bromozinc-α,α-difluoroacetate in the presence of ...
Scheme 22: Reformatsky reaction of aldehydes with an enolate equivalent prepared from phenyl isocyanate and CH2...
Scheme 23: Domino aza-Reformatsky/cyclization reactions of imines with ethyl dibromofluoroacetate in the prese...
Scheme 24: Domino aza-Reformatsky/cyclization reactions of imines with ethyl bromodifluoroacetate in the prese...
Scheme 25: Aza-Reformatsky reactions of cyclic imines with ethyl iodoacetate in the presence of a chiral diary...
Scheme 26: Mechanism for aza-Reformatsky reaction of cyclic imines with ethyl iodoacetate in the presence of a...
Scheme 27: Aza-Reformatsky reaction of dibenzo[b,f][1,4]oxazepines and dibenzo[b,f][1,4]thiazepine with ethyl ...
Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides
- Masanori Inaba,
- Tatsuya Sakai,
- Shun Shinada,
- Tsuyuka Sugiishi,
- Yuta Nishina,
- Norio Shibata and
- Hideki Amii
Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12
- practical method for the synthesis of C3-perfluoroalkyl-substituted phthalides in a one-pot manner. Upon treatment of KF or triethylamine, 2-cyanobenzaldehyde reacted with (perfluoroalkyl)trimethylsilanes via nucleophilic addition and subsequent intramolecular cyclization to give perfluoroalkylphthalides in
Graphical Abstract
Scheme 1: Phthalide and fluorinated phthalides (1).
Scheme 2: Plausible reaction mechanism for the formation of phthalide 1a.
Scheme 3: Synthesis of fluorinated phthalides 1.
Scheme 4: Asymmetric synthesis of 1a using a chiral auxiliary.
Scheme 5: Catalytic asymmetric synthesis of 1a.
Progress in copper-catalyzed trifluoromethylation
- Guan-bao Li,
- Chao Zhang,
- Chun Song and
- Yu-dao Ma
Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11
- tetrahydroisoquinoline with DDQ generates dihydroquinoline salt A. Next, CuCF3, generated by the reaction of CuI and CF3TMS/KF, undergoes a nucleophilic addition with A affording the desired products and the copper salt. The generated copper salt would be reused to form CuCF3 in the nucleophilic step again. So, only a
Graphical Abstract
Figure 1: Selected examples of pharmaceutical and agrochemical compounds containing the trifluoromethyl group....
Scheme 1: Introduction of a diamine into copper-catalyzed trifluoromethylation of aryl iodides.
Scheme 2: Addition of a Lewis acid into copper-catalyzed trifluoromethylation of aryl iodides and the propose...
Scheme 3: Trifluoromethylation of heteroaromatic compounds using S-(trifluoromethyl)diphenylsulfonium salts a...
Scheme 4: The preparation of a new trifluoromethylation reagent and its application in trifluoromethylation o...
Scheme 5: Trifluoromethylation of aryl iodides using CF3CO2Na as a trifluoromethyl source.
Scheme 6: Trifluoromethylation of aryl iodides using MTFA as a trifluoromethyl source.
Scheme 7: Trifluoromethylation of aryl iodides using CF3CO2K as a trifluoromethyl source.
Scheme 8: Trifluoromethylation of aryl iodides and heteroaryl bromides using [Cu(phen)(O2CCF3)] as a trifluor...
Scheme 9: Trifluoromethylation of aryl iodides with DFPB and the proposed mechanism.
Scheme 10: Trifluoromethylation of aryl iodides using TCDA as a trifluoromethyl source. Reaction conditions: [...
Scheme 11: The mechanism of trifluoromethylation using Cu(II)(O2CCF2SO2F)2 as a trifluoromethyl source.
Scheme 12: Trifluoromethylation of benzyl bromide reported by Shibata’s group.
Scheme 13: Trifluoromethylation of allylic halides and propargylic halides reported by the group of Nishibayas...
Scheme 14: Trifluoromethylation of propargylic halides reported by the group of Nishibayashi.
Scheme 15: Trifluoromethylation of alkyl halides reported by Nishibayashi’s group.
Scheme 16: Trifluoromethylation of pinacol esters reported by the group of Gooßen.
Scheme 17: Trifluoromethylation of primary and secondary alkylboronic acids reported by the group of Fu.
Scheme 18: Trifluoromethylation of boronic acid derivatives reported by the group of Liu.
Scheme 19: Trifluoromethylation of organotrifluoroborates reported by the group of Huang.
Scheme 20: Trifluoromethylation of aryl- and vinylboronic acids reported by the group of Shibata.
Scheme 21: Trifluoromethylation of arylboronic acids via the merger of photoredox and Cu catalysis.
Scheme 22: Trifluoromethylation of arylboronic acids reported by Sanford’s group. Isolated yield. aYields dete...
Scheme 23: Trifluoromethylation of arylboronic acids and vinylboronic acids reported by the group of Beller. Y...
Scheme 24: Copper-mediated Sandmeyer type trifluoromethylation using Umemoto’s reagent as a trifluoromethylati...
Scheme 25: Copper-mediated Sandmeyer type trifluoromethylation using TMSCF3 as a trifluoromethylation reagent ...
Scheme 26: One-pot Sandmeyer trifluoromethylation reported by the group of Gooßen.
Scheme 27: Copper-catalyzed trifluoromethylation of arenediazonium salts in aqueous media.
Scheme 28: Copper-mediated Sandmeyer trifluoromethylation using Langlois’ reagent as a trifluoromethyl source ...
Scheme 29: Trifluoromethylation of terminal alkenes reported by the group of Liu.
Scheme 30: Trifluoromethylation of terminal alkenes reported by the group of Wang.
Scheme 31: Trifluoromethylation of tetrahydroisoquinoline derivatives reported by Li and the proposed mechanis...
Scheme 32: Trifluoromethylation of phenol derivatives reported by the group of Hamashima.
Scheme 33: Trifluoromethylation of hydrazones reported by the group of Baudoin and the proposed mechanism.
Scheme 34: Trifluoromethylation of benzamides reported by the group of Tan.
Scheme 35: Trifluoromethylation of heteroarenes and electron-deficient arenes reported by the group of Qing an...
Scheme 36: Trifluoromethylation of N-aryl acrylamides using CF3SO2Na as a trifluoromethyl source.
Scheme 37: Trifluoromethylation of aryl(heteroaryl)enol acetates using CF3SO2Na as the source of CF3 and the p...
Scheme 38: Trifluoromethylation of imidazoheterocycles using CF3SO2Na as a trifluoromethyl source and the prop...
Scheme 39: Copper-mediated trifluoromethylation of terminal alkynes using TMSCF3 as a trifluoromethyl source a...
Scheme 40: Improved copper-mediated trifluoromethylation of terminal alkynes reported by the group of Qing.
Scheme 41: Copper-catalyzed trifluoromethylation of terminal alkynes reported by the group of Qing.
Scheme 42: Copper-catalyzed trifluoromethylation of terminal alkynes using Togni’s reagent and the proposed me...
Scheme 43: Copper-catalyzed trifluoromethylation of terminal alkynes using Umemoto’s reagent reported by the g...
Scheme 44: Copper-catalyzed trifluoromethylation of 3-arylprop-1-ynes reported by Xiao and Lin and the propose...
Gram-scale preparation of negative-type liquid crystals with a CF2CF2-carbocycle unit via an improved short-step synthetic protocol
- Tatsuya Kumon,
- Shohei Hashishita,
- Takumi Kida,
- Shigeyuki Yamada,
- Takashi Ishihara and
- Tsutomu Konno
Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10
- . The latter could be constructed through ring-closing metathesis of the corresponding precursor, e.g., 4,4,5,5-tetrafluoroocta-1,7-diene 5, using a Grubbs' catalyst. The octa-1,7-diene 5 could be obtained through a nucleophilic addition of a vinylic Grignard reagent to the γ-keto ester 6. Lastly, the γ
- afford the corresponding octa-1,7-diene 5a in only 46% yield. In this case, the 5-membered lactol derivative 8a was also obtained in 42% yield as a side-product. A proposed reaction mechanism for the formation of 5a and 8a is shown in Scheme 3. Thus, the nucleophilic addition reactions of vinylmagnesium
Graphical Abstract
Figure 1: Typical examples of previously reported negative-type liquid crystals containing a CF2CF2-carbocycl...
Scheme 1: Improved short-step synthetic protocol for multicyclic mesogens 1 and 2.
Scheme 2: Short-step approach to CF2CF2-containing carbocycles.
Figure 2: (a) Expected products of over-reaction in the Grignard reaction of dimethyl tetrafluorosuccinate (7...
Scheme 3: Mechanism for the reaction of γ-keto ester 6 with vinyl Grignard reagents.
Scheme 4: First multigram-scale preparation of CF2CF2-containing multicyclic mesogens.
Scheme 5: Stereochemical assignment of the ring-closing metathesis products.
Conformational preferences of α-fluoroketones may influence their reactivity
- Graham Pattison
Beilstein J. Org. Chem. 2017, 13, 2915–2921, doi:10.3762/bjoc.13.284
- ; Introduction α-Halogenated ketones are widely used electrophiles in organic synthesis, being highly reactive in both nucleophilic addition to the carbonyl group and in SN2 nucleophilic displacements [1]. Our research group has recently been exploring the synthesis and reactivity of α-fluorinated ketones [2][3
- electrophiles available to synthetic chemists for SN2 substitution [5]. The orbital overlap in α-halogenated ketones also provides activation to the carbonyl group, making it more reactive towards nucleophilic addition than non-halogenated carbonyl compounds [6]. However, relatively little work has been
- reactivity we wished to measure the relative reactivity of various α-halogenated ketones towards nucleophilic addition. As these are highly reactive systems obtaining rate profiles can be difficult due to the short time-scales for measurements, so instead relative reactivity was measured through a series of
Graphical Abstract
Scheme 1: Relative reactivity of α-fluoroacetophenone to α-chloroacetophenone and α-bromoacetophenone.
Scheme 2: Competitive reduction of haloacetophenones and acetophenone.
Figure 1: Conformational energy profiles of halogenated acetophenones (a) in gas phase; (b) in EtOH; (c) over...
Figure 2: Optimised gas phase geometries of (a) α-fluoroacetophenone and (b) α-chloroacetophenone emphasising...
Figure 3: Most stable conformations of (a) α-fluoroacetophenone and (b) α-chloroacetophenone in ethanol.
Figure 4: Expected reactive conformation of halo-acetophenones.
Figure 5: Orbital interactions in gauche- and cis-conformations of haloacetophenones.
Figure 6: Variation of dipole moment with angle for haloacetophenones.
Figure 7: Highest energy conformation of fluoroacetophenone, emphasizing the closeness of approach of fluorin...
Scheme 3: Competitive reduction of fluoroacetone and chloroacetone.
Figure 8: Conformational energy profiles of halogenated acetones in gas phase and in MeOH.
Figure 9: Overlay of conformational energy profiles of fluoroacetone and fluoroacetophenone.
Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides
- Irwan Iskandar Roslan,
- Kian-Hong Ng,
- Gaik-Khuan Chuah and
- Stephan Jaenicke
Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270
- -aminobenzothiazole (1a) via an Ortoleva–King type of reaction forms B [96][97]. This is followed by a nucleophilic addition and dehydration to form C. Upon deprotonation of the acidic proton at C by KOt-Bu, the desired product 3a is formed with release of KBr and tert-butanol. As proposed by Zeitler’s group, the
Graphical Abstract
Scheme 1: Two different intermolecular cyclization pathways controlled by reagents used.
Scheme 2: Scope of reaction. Reaction conditions: 1 (1.2 mmol), 2 (1.0 mmol), KOt-Bu (2 mmol), in 3 mL CBrCl3...
Scheme 3: Scope of the reaction. Reaction conditions: 1 (1.0 mmol), 2 (1.5 mmol), In(OTf)3 (0.1 mmol), in 1.5...
Scheme 4: Control experiments.
Figure 1: Proposed mechanism (benzo[d]imidazo[2,1-b]thiazoles).
Figure 2: Proposed mechanism (benzo[4,5]thiazolo[3,2-a]pyrimidin-4-ones).
Vinylphosphonium and 2-aminovinylphosphonium salts – preparation and applications in organic synthesis
- Anna Kuźnik,
- Roman Mazurkiewicz and
- Beata Fryczkowska
Beilstein J. Org. Chem. 2017, 13, 2710–2738, doi:10.3762/bjoc.13.269
- in their structures. Keywords: 2-aminovinylphosphonium salts; nucleophilic addition; phosphorus ylides; vinylphosphonium salts; Wittig reaction; Introduction Vinylphosphonium salts have been known for a long time, although significant interest in these compounds dates back to 1964, when Schweizer
- and Appleyard only postulated that the reaction between the benzoate anion and 2-propynyltriphenylphosphonium bromide (24) led to a 2-benzoyloxyvinylphosphonium salt 26 (Scheme 17) [32]. Several years later, Schweizer et al. discovered that the nucleophilic addition of amines to 2
- -benzoyloxyvinylphosphonium bromide from 2-propynyltriphenylphosphonium bromide. Synthesis of 2-aminovinylphosphonium salts via nucleophilic addition of amines to 2-propynyltriphenylphosphonium bromide. Deacylation of 2-(N-acylamino)vinylphosphonium chlorides to 2-aminovinylphosphonium salts. Resonance structures of 2
Graphical Abstract
Scheme 1: Generation of phosphorus ylides from vinylphosphonium salts.
Scheme 2: Intramolecular Wittig reaction with the use of vinylphosphonium salts.
Scheme 3: Alkylation of diphenylvinylphosphine with methyl or benzyl iodide.
Scheme 4: Methylation of isopropenyldiphenylphosphine with methyl iodide.
Scheme 5: Alkylation of phosphines with allyl halide derivatives and subsequent isomerization of intermediate...
Scheme 6: Alkylation of triphenylphosphine with vinyl triflates in the presence of (Ph3P)4Pd.
Scheme 7: Mechanism of alkylation of triphenylphosphine with vinyl triflates in the presence of (Ph3P)4Pd as ...
Scheme 8: β-Elimination of phenol from β-phenoxyethyltriphenylphosphonium bromide.
Scheme 9: β-Elimination of phenol from β-phenoxyethylphosphonium salts in an alkaline environment.
Scheme 10: Synthesis and subsequent dehydrohalogenation of α-bromoethylphosphonium bromide.
Scheme 11: Synthesis of tributylvinylphosphonium iodides via Peterson-type olefination of α-trimethylsilylphos...
Scheme 12: Synthesis of 1-cycloalkenetriphenylphosphonium salts by electrochemical oxidation of triphenylphosp...
Scheme 13: Suggested mechanism for the electrochemical synthesis of 1-cycloalkenetriphenylphosphonium salts.
Scheme 14: Generation of α,β-(dialkoxycarbonyl)vinylphosphonium salts by addition of triphenylphosphine to ace...
Scheme 15: Synthesis of 2-(N-acylamino)vinylphosphonium halides by imidoylation of β-carbonyl ylides with imid...
Scheme 16: Imidoylation of β-carbonyl ylides with imidoyl halides generated in situ.
Scheme 17: Synthesis of 2-benzoyloxyvinylphosphonium bromide from 2-propynyltriphenylphosphonium bromide.
Scheme 18: Synthesis of 2-aminovinylphosphonium salts via nucleophilic addition of amines to 2-propynyltriphen...
Scheme 19: Deacylation of 2-(N-acylamino)vinylphosphonium chlorides to 2-aminovinylphosphonium salts.
Scheme 20: Resonance structures of 2-aminovinylphosphonium salts and tautomeric equilibrium between aminovinyl...
Scheme 21: Synthesis of 2-aminovinylphosphonium salts by reaction of (formylmethyl)triphenylphosphonium chlori...
Scheme 22: Generation of ylides by reaction of vinyltriphenylphosphonium bromide with nucleophiles and their s...
Scheme 23: Intermolecular Wittig reaction with the use of vinylphosphonium bromide and organocopper compounds ...
Scheme 24: Intermolecular Wittig reaction with the use of ylides generated from vinylphosphonium bromides and ...
Scheme 25: Direct transformation of vinylphosphonium salts into ylides in the presence of potassium tert-butox...
Scheme 26: A general method for synthesis of carbo- and heterocyclic systems by the intramolecular Wittig reac...
Scheme 27: Synthesis of 2H-chromene by reaction of vinyltriphenylphosphonium bromide with sodium 2-formylpheno...
Scheme 28: Synthesis of 2,5-dihydro-2,3-dimethylfuran by reaction of vinylphosphonium bromide with 3-hydroxy-2...
Scheme 29: Synthesis of 2H-chromene and 2,5-dihydrofuran derivatives in the intramolecular Wittig reaction wit...
Scheme 30: Enantioselective synthesis of 3,6-dihydropyran derivatives from vinylphosphonium bromide and enanti...
Scheme 31: Synthesis of 2,5-dihydrothiophene derivatives in the intramolecular Wittig reaction from vinylphosp...
Scheme 32: Synthesis of bicyclic pyrrole derivatives in the reaction of vinylphosphonium halides and 2-pyrrolo...
Scheme 33: Stereoselective synthesis of bicyclic 2-pyrrolidinone derivatives in the reaction of vinylphosphoni...
Scheme 34: Stereoselective synthesis of 3-pyrroline derivatives in the intramolecular Wittig reaction from vin...
Scheme 35: Synthesis of cyclic alkenes in the intramolecular Wittig reaction from vinylphosphonium bromide and...
Scheme 36: Synthesis of 1,3-cyclohexadienes by reaction of 1,3-butadienyltriphenylphosphonium bromide with eno...
Scheme 37: Synthesis of bicyclo[3.3.0]octenes by reaction of vinylphosphonium salts with cyclic diketoester.
Scheme 38: Synthesis of quinoline derivatives in the intramolecular Wittig reaction from 2-(2-acylphenylamino)...
Scheme 39: Stereoselective synthesis of γ-aminobutyric acid in the intermolecular Wittig reaction from chiral ...
Scheme 40: Synthesis of allylamines in the intermolecular Wittig reaction from 2-aminovinylphosphonium bromide...
Scheme 41: A general route towards α,β-di(alkoxycarbonyl)vinylphosphonium salts and their subsequent possible ...
Scheme 42: Generation of resonance-stabilized phosphorus ylides via the reaction of triphenylphosphine with di...
Scheme 43: Synthesis of resonance-stabilized phosphorus ylides in the reaction of triphenylphosphine, dialkyl ...
Scheme 44: Synthesis of resonance-stabilized phosphorus ylides via the reaction of triphenylphosphine with dia...
Scheme 45: Generation of resonance-stabilized phosphorus ylides in the reaction of acetylenedicarboxylate, tri...
Scheme 46: Synthesis of resonance-stabilized phosphorus ylides via the reaction of dialkyl acetylenedicarboxyl...
Scheme 47: Synthesis of resonance-stabilized ylides derived from semicarbazones, aromatic amides, and 3-(aryls...
Scheme 48: Synthesis of resonance-stabilized ylides via the reaction of triphenylphosphine with dialkyl acetyl...
Scheme 49: Synthesis of resonance-stabilized ylides in the reaction of triphenylphosphine, dialkyl acetylenedi...
Scheme 50: Synthesis of N-acylated α,β-unsaturated γ-lactams via resonance-stabilized phosphorus ylides derive...
Scheme 51: Synthesis of resonance-stabilized phosphorus ylides derived from 6-amino-N,N'-dimethyluracil and th...
Scheme 52: Generation of resonance-stabilized phosphorus ylides in the reaction of triphenylphosphine, dialkyl...
Scheme 53: Synthesis of resonance-stabilized phosphorus ylides via the reaction of triphenylphosphine with dia...
Scheme 54: Synthesis of 1,3-dienes via intramolecular Wittig reaction with the use of resonance-stabilized yli...
Scheme 55: Synthesis of 1,3-dienes in the intramolecular Wittig reaction from ylides generated from dimethyl a...
Scheme 56: Synthesis of 4-(2-quinolyl)cyclobutene-1,2,3-tricarboxylic acid triesters and isomeric cyclopenteno...
Scheme 57: Synthesis of 4-arylquinolines via resonance-stabilized ylides in the intramolecular Wittig reaction....
Scheme 58: Synthesis of furan derivatives via resonance-stabilized ylides in the intramolecular Wittig reactio...
Scheme 59: Synthesis of 1,3-indanedione derivatives via resonance-stabilized ylides in the intermolecular Witt...
Scheme 60: Synthesis of coumarin derivatives via nucleophilic displacement of the triphenylphosphonium group i...
Scheme 61: Synthesis of 6-formylcoumarin derivatives and their application in the synthesis of dyads.
Scheme 62: Synthesis of di- and tricyclic coumarin derivatives in the reaction of pyrocatechol with two vinylp...
Scheme 63: Synthesis of mono-, di-, and tricyclic derivatives in the reaction of pyrogallol with one or two vi...
Scheme 64: Synthesis of 1,4-benzoxazine derivative by nucleophilic displacement of the triphenylphosphonium gr...
Scheme 65: Synthesis of 7-oxo-7H-pyrido[1,2,3-cd]perimidine derivative via nucleophilic displacement of the tr...
Scheme 66: Application of vinylphosphonium salts in the Diels–Alder reaction with dienes.
Scheme 67: Synthesis of pyrroline derivatives from vinylphosphonium bromide and 5-(4H)-oxazolones.
Scheme 68: Synthesis of pyrrole derivatives in the reactions of vinyltriphenylphosphonium bromide with protona...
Scheme 69: Synthesis of dialkyl 2-(alkylamino)-5-aryl-3,4-furanedicarboxylates via intermediate α,β-di(alkoxyc...
Scheme 70: Synthesis of 1,4-benzoxazine derivatives from acetylenedicarboxylates, phosphines, and 1-nitroso-2-...
Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate
- Clément Ghiazza,
- Anis Tlili and
- Thierry Billard
Beilstein J. Org. Chem. 2017, 13, 2626–2630, doi:10.3762/bjoc.13.260
- the nucleophilic addition of Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate, a stable and easy-to-handle reagent, to alkynes is described. This reaction provides trifluoromethylselenylated vinyl sulfones with good results and the method was extended also to higher fluorinated homologs. The
- obtained compounds are valuable building blocks for further syntheses of fluoroalkylselenolated molecules. Keywords: alkynes; nucleophilic addition; perfluoroalkylselenolation; Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate; trifluoromethylselenolation; Introduction Over the last decades
Graphical Abstract
Scheme 1: Electrophilic addition of 1a to alkynes. Yields shown are those of isolated products; yields determ...
Figure 1: Single-crystal X-ray structure of 3a.
Scheme 2: Mechanism proposal.
Scheme 3: Perfluoroalkylselenolation of alkynes. Yields shown are those of isolated products; yields determin...
Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones
- Sergii V. Melnykov,
- Andrii S. Pataman,
- Yurii V. Dmytriv,
- Svitlana V. Shishkina,
- Mykhailo V. Vovk and
- Volodymyr A. Sukach
Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259
- preparation of acid 3 homologues (with a methylene linker between the carboxylic group and the pyrimidine ring) and their isomers resulting from two alternative regioselective pathways for the decarboxylative nucleophilic addition of malonic acid and its mono(thio)esters. Results and Discussion We first
- -step mechanism of the decarboxylative nucleophilic addition which is characterized by a faster decarboxylation of kinetically-controlled Michael-type intermediates in high-polar solvents. Though malonic monoester 1a appears to be similar to malonic acid in reactivity towards compounds 2, it produces
Graphical Abstract
Figure 1: Summary of the present study.
Scheme 1: Hydrogenation of compounds 4–6 and preparation of N1(3)-unsubstituted compounds 9–11d.
Figure 2: Molecular structure of compound 11b. Two enantiomers form a heterochiral dimer in the crystal state...
Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics
- Matthias Wünsch,
- David Schröder,
- Tanja Fröhr,
- Lisa Teichmann,
- Sebastian Hedwig,
- Nils Janson,
- Clara Belu,
- Jasmin Simon,
- Shari Heidemeyer,
- Philipp Holtkamp,
- Jens Rudlof,
- Lennard Klemme,
- Alessa Hinzmann,
- Beate Neumann,
- Hans-Georg Stammler and
- Norbert Sewald
Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240
- propargylamines by nucleophilic addition. The synthesis of propargylamines by diastereoselective reductive amination requires alkynyl ketones, which are difficult to prepare and are unstable towards reductive conditions. In approach I, organometallic nucleophiles are added to N-sulfinyl propargylimines, derived
- adjacent protons considerably. In the precursor sulfinylimines 5 of the target propargylamines the acidity of the protons of the methylene moiety is further increased by the electron-withdrawing effect of the adjacent sulfinyl imino moiety. Thus, the nucleophilic addition of (trimethylsilyl)ethynyllithium
- structure of fluorinated propargylamines occurs in important drugs, like HIV protease inhibitor DPC 961 and its analogues [78][79][80][81][82][83], particular effort was put on the synthesis of N-sulfinyl propargylamine 7k. Because of the poor electrophilicity of imines 5, the nucleophilic addition of
Graphical Abstract
Figure 1: Concept of carboxylic acid or amide bond replacement on the basis of an alkyne moiety.
Figure 2: Selection of reactions based on propargylamines as precursors. a) Intramolecular Pauson–Khand react...
Figure 3: Two different approaches for the stereoselective de novo synthesis of propargylamines using Ellman’...
Figure 4: Synthesis of propargylamines 4a and 4b by introducing the side chain as nucleophile. (a) HC≡CCH2OH,...
Figure 5: Reaction of N-sulfinylimine 5h with (trimethylsilyl)ethynyllithium. (a) GP-3 or GP-4. (b) Aqueous w...
Figure 6: Side reactions observed in the course of the conversion of highly electrophilic sulfinylimines 5. (...
Figure 7: a) Possible transition states TI and TII for the transfer of the methyl moiety from AlMe3 to the im...
Figure 8: Base-induced rearrangement of propargylamines bearing electron-withdrawing substituents.
Figure 9: Base-catalyzed rearrangement of propargylamines 11 to α,β-unsaturated imines 12. A) Reaction scheme...
