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Search for "[3,3]-sigmatropic rearrangement" in Full Text gives 23 result(s) in Beilstein Journal of Organic Chemistry.
Synthetic study toward tridachiapyrone B
- Morgan Cormier,
- Florian Hernvann and
- Michaël De Paolis
Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183
- by destabilizing the negative charge of the anion (Scheme 7c). Simply generated with Triton B (benzyltrimethylammonium hydroxide), the alcoholate of 17 smoothly (−20 °C to rt) underwent the [3,3]-sigmatropic rearrangement (75% conversion) directly affording 2,5-cyclohexadienone E-19 which was
Graphical Abstract
Scheme 1: Routes to crispatene, photodeoxytridachione, aureothin, and tridachiapyrone B.
Scheme 2: Desymmetrization of 2.
Scheme 3: Addition of lithiocyclopentadiene to pyrone 2.
Scheme 4: Plan to reach 2,5-cyclohexadienone 5.
Scheme 5: Preparation of 2,5-cyclohexadienone 5.
Scheme 6: Attempts to perform the conjugate addition.
Scheme 7: Updated route to tridachiapyrone B.
Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds
- Alemayehu Gashaw Woldegiorgis and
- Xufeng Lin
Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185
- ′-binaphthalenes (BINAMs) from achiral N,N′-binaphthylhydrazines (Scheme 1). In the presence of chiral phosphoric acids (CPA 1), the reaction undergoes a simple [3,3]-sigmatropic rearrangement, giving the corresponding products 2 in good yield (up to 88%) and enantioselectivity (up to 93:7 er). The density
- functional calculations showed that the chiral phosphoric acid proton forms an H-bond with nitrogen atoms of 1 and the phosphate acts as a chiral counterion, resulting in a [3,3]-sigmatropic rearrangement with controlled stereoselectivity [14][41]. In 2017, Tan and co-workers developed an organocatalytic
- materials and supramolecules. Important chiral phosphoric acid scaffolds used in this review. Atroposelective aryl–aryl-bond formation by employing a facile [3,3]-sigmatropic rearrangement. Atroposelective synthesis of axially chiral biaryl amino alcohols 5. The enantioselective reaction of quinone and 2
Graphical Abstract
Figure 1: Representative examples of axially chiral biaryls, heterobiaryls, spiranes and allenes as ligands a...
Figure 2: Selected examples of axially chiral drugs and bioactive molecules.
Figure 3: Axially chiral functional materials and supramolecules.
Figure 4: Important chiral phosphoric acid scaffolds used in this review.
Scheme 1: Atroposelective aryl–aryl-bond formation by employing a facile [3,3]-sigmatropic rearrangement.
Scheme 2: Atroposelective synthesis of axially chiral biaryl amino alcohols 5.
Scheme 3: The enantioselective reaction of quinone and 2-naphthol derivatives.
Scheme 4: Enantioselective synthesis of multisubstituted biaryls.
Scheme 5: Enantioselective synthesis of axially chiral quinoline-derived biaryl atropisomers mediated by chir...
Scheme 6: Pd-Catalyzed atroposelective C–H olefination of biarylamines.
Scheme 7: Palladium-catalyzed directed atroposelective C–H allylation.
Scheme 8: Enantioselective synthesis of axially chiral (a) aryl indoles and (b) biaryldiols.
Scheme 9: Asymmetric arylation of indoles enabled by azo groups.
Scheme 10: Proposed mechanism for the asymmetric arylation of indoles.
Scheme 11: Enantioselective synthesis of axially chiral N-arylindoles [38].
Scheme 12: Enantioselective [3 + 2] formal cycloaddition and central-to-axial chirality conversion.
Scheme 13: Organocatalytic atroposelective arene functionalization of nitrosonaphthalene with indoles.
Scheme 14: Proposed reaction mechanism for the atroposelective arene functionalization of nitrosonaphthalenes.
Scheme 15: Asymmetric construction of axially chiral naphthylindoles [65].
Scheme 16: Enantioselective synthesis of axially chiral 3,3’-bisindoles [66].
Scheme 17: Atroposelective synthesis of 3,3’-bisiindoles bearing axial and central chirality.
Scheme 18: Enantioselective synthesis of axially chiral 3,3’-bisindoles bearing single axial chirality.
Scheme 19: Enantioselective reaction of azonaphthalenes with various pyrazolones.
Scheme 20: Enantioselective and atroposelective synthesis of axially chiral N-arylcarbazoles [73].
Scheme 21: Atroposelective cyclodehydration reaction.
Scheme 22: Atroposelective construction of axially chiral N-arylbenzimidazoles [78].
Scheme 23: Proposed reaction mechanism for the atroposelective synthesis of axially chiral N-arylbenzimidazole...
Scheme 24: Atroposelective synthesis of axially chiral arylpyrroles [21].
Scheme 25: Synthesis of axially chiral arylquinazolinones and its reaction pathway [35].
Scheme 26: Synthesis of axially chiral aryquinoline by Friedländer heteroannulation reaction and its proposed...
Scheme 27: Povarov cycloaddition–oxidative chirality conversion process.
Scheme 28: Atroposelective synthesis of oxindole-based axially chiral styrenes via kinetic resolution.
Scheme 29: Synthesis of axially chiral alkene-indole frame works [45].
Scheme 30: Proposed reaction mechanism for axially chiral alkene-indoles.
Scheme 31: Atroposelective C–H aminations of N-aryl-2-naphthylamines with azodicarboxylates.
Scheme 32: Synthesis of brominated atropisomeric N-arylquinoids.
Scheme 33: The enantioselective syntheses of axially chiral SPINOL derivatives.
Scheme 34: γ-Addition reaction of various 2,3-disubstituted indoles to β,γ-alkynyl-α-imino esters.
Scheme 35: Regio- and stereoselective γ-addition reactions of isoxazol-5(4H)-ones to β,γ-alkynyl-α-imino ester...
Scheme 36: Synthesis of chiral tetrasubstituted allenes and naphthopyrans.
Scheme 37: Asymmetric remote 1,8-conjugate additions of thiazolones and azlactones to propargyl alcohols.
Scheme 38: Synthesis of chiral allenes from 1-substituted 2-naphthols [107].
Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years
- Asha Budakoti,
- Pradip Kumar Mondal,
- Prachi Verma and
- Jagadish Khamrai
Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77
- cyclization and minimizes the competitive 2-oxonia-[3,3]-sigmatropic rearrangement pathway. The reaction was highly stereoselective and afforded the cis-2,6-dihydropyran in the presence of Lewis acid FeCl3. From DFT calculations, the authors concluded that the Prins product is formed more rapidly than the α
- formal 2-oxonia-[3,3]-sigmatropic rearrangement. Furthermore, Markó and co-workers successfully synthesized 2,6-anti-configured THP starting from allylsilane 245, following diethylaluminium chloride-promoted ene reaction and condensation with an aldehyde 246 [102]. Expected ene adduct 247 was obtained as
Graphical Abstract
Scheme 1: General strategy for the synthesis of THPs.
Scheme 2: Developments towards the Prins cyclization.
Scheme 3: General stereochemical outcome of the Prins cyclization.
Scheme 4: Regioselectivity in the Prins cyclization.
Scheme 5: Mechanism of the oxonia-Cope reaction in the Prins cyclization.
Scheme 6: Cyclization of electron-deficient enantioenriched alcohol 27.
Scheme 7: Partial racemization through 2-oxonia-Cope allyl transfer.
Scheme 8: Partial racemization by reversible 2-oxonia-Cope rearrangement.
Scheme 9: Rychnovsky modification of the Prins cyclization.
Scheme 10: Synthesis of (−)-centrolobine and the C22–C26 unit of phorboxazole A.
Scheme 11: Axially selective Prins cyclization by Rychnovsky et al.
Scheme 12: Mechanism for the axially selectivity Prins cyclization.
Scheme 13: Mukaiyama aldol–Prins cyclization reaction.
Scheme 14: Application of the aldol–Prins reaction.
Scheme 15: Hart and Bennet's acid-promoted Prins cyclization.
Scheme 16: Tetrahydropyran core of polycarvernoside A as well as (−)-clavoslide A and D.
Scheme 17: Scheidt and co-workers’ route to tetrahydropyran-4-one.
Scheme 18: Mechanism for the Lewis acid-catalyzed synthesis of tetrahydropyran-4-one.
Scheme 19: Hoveyda and co-workers’ strategy for 2,6-disubstituted 4-methylenetetrahydropyran.
Scheme 20: Funk and Cossey’s ene-carbamates strategy.
Scheme 21: Yadav and Kumar’s cyclopropane strategy for THP synthesis.
Scheme 22: 2-Arylcylopropylmethanolin in centrolobine synthesis.
Scheme 23: Yadav and co-workers’ strategy for the synthesis of THP.
Scheme 24: Yadav and co-workers’ Prins–Ritter reaction sequence for 4-amidotetrahydropyran.
Scheme 25: Yadav and co-workers’ strategy to prelactones B, C, and V.
Scheme 26: Yadav and co-workers’ strategy for the synthesis of (±)-centrolobine.
Scheme 27: Loh and co-workers’ strategy for the synthesis of zampanolide and dactylolide.
Scheme 28: Loh and Chan’s strategy for THP synthesis.
Scheme 29: Prins cyclization of cyclohexanecarboxaldehyde.
Scheme 30: Prins cyclization of methyl ricinoleate (127) and benzaldehyde (88).
Scheme 31: AlCl3-catalyzed cyclization of homoallylic alcohol 129 and aldehyde 130.
Scheme 32: Martín and co-workers’ stereoselective approach for the synthesis of highly substituted tetrahydrop...
Scheme 33: Ene-IMSC strategy by Marko and Leroy for the synthesis of tetrahydropyran.
Scheme 34: Marko and Leroy’s strategy for the synthesis of tetrahydropyrans 146.
Scheme 35: Sakurai dimerization/macrolactonization reaction for the synthesis of cyanolide A.
Scheme 36: Hoye and Hu’s synthesis of (−)-dactyloide by intramolecular Sakurai cyclization.
Scheme 37: Minehan and co-workers’ strategy for the synthesis of THPs 157.
Scheme 38: Yu and co-workers’ allylic transfer strategy for the construction of tetrahydropyran 161.
Scheme 39: Reactivity enhancement in intramolecular Prins cyclization.
Scheme 40: Floreancig and co-workers’ Prins cyclization strategy to (+)-dactyloide.
Scheme 41: Panek and Huang’s DHP synthesis from crotylsilanes: a general strategy.
Scheme 42: Panek and Huang’s DHP synthesis from syn-crotylsilanes.
Scheme 43: Panek and Huang’s DHP synthesis from anti-crotylsilanes.
Scheme 44: Roush and co-workers’ [4 + 2]-annulation strategy for DHP synthesis [82].
Scheme 45: TMSOTf-promoted annulation reaction.
Scheme 46: Dobb and co-workers’ synthesis of DHP.
Scheme 47: BiBr3-promoted tandem silyl-Prins reaction by Hinkle et al.
Scheme 48: Substrate scope of Hinkle and co-workers’ strategy.
Scheme 49: Cho and co-workers’ strategy for 2,6 disubstituted 3,4-dimethylene-THP.
Scheme 50: Furman and co-workers’ THP synthesis from propargylsilane.
Scheme 51: THP synthesis from silyl enol ethers.
Scheme 52: Rychnovsky and co-workers’ strategy for THP synthesis from hydroxy-substituted silyl enol ethers.
Scheme 53: Li and co-workers’ germinal bissilyl Prins cyclization strategy to (−)-exiguolide.
Scheme 54: Xu and co-workers’ hydroiodination strategy for THP.
Scheme 55: Wang and co-workers’ strategy for tetrahydropyran synthesis.
Scheme 56: FeCl3-catalyzed synthesis of DHP from alkynylsilane alcohol.
Scheme 57: Martín, Padrón, and co-workers’ proposed mechanism of alkynylsilane Prins cyclization for the synth...
Scheme 58: Marko and co-workers’ synthesis of 2,6-anti-configured tetrahydropyran.
Scheme 59: Loh and co-workers’ strategy for 2,6-syn-tetrahydropyrans.
Scheme 60: Loh and co-workers’ strategy for anti-THP synthesis.
Scheme 61: Cha and co-workers’ strategy for trans-2,6-tetrahydropyran.
Scheme 62: Mechanism proposed by Cha et al.
Scheme 63: TiCl4-mediated cyclization to trans-THP.
Scheme 64: Feng and co-workers’ FeCl3-catalyzed Prins cyclization strategy to 4-hydroxy-substituted THP.
Scheme 65: Selectivity profile of the Prins cyclization under participation of an iron ligand.
Scheme 66: Sequential reactions involving Prins cyclization.
Scheme 67: Banerjee and co-workers’ strategy of Prins cyclization from cyclopropane carbaldehydes and propargy...
Scheme 68: Mullen and Gagné's (R)-[(tolBINAP)Pt(NC6F5)2][SbF6]2-catalyzed asymmetric Prins cyclization strateg...
Scheme 69: Yu and co-workers’ DDQ-catalyzed asymmetric Prins cyclization strategy to trisubstituted THPs.
Scheme 70: Lalli and Weghe’s chiral-Brønsted-acid- and achiral-Lewis-acid-promoted asymmetric Prins cyclizatio...
Scheme 71: List and co-workers’ iIDP Brønsted acid-promoted asymmetric Prins cyclization strategy.
Scheme 72: Zhou and co-workers’ strategy for chiral phosphoric acid (CPA)-catalyzed cascade Prins cyclization.
Scheme 73: List and co-workers’ approach for asymmetric Prins cyclization using chiral imidodiphosphoric acid ...
Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine
- Dimas J. P. Lima,
- Antonio E. G. Santana,
- Michael A. Birkett and
- Ricardo S. Porto
Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4
- approach consisted of a 3,3-sigmatropic rearrangement to give an all-carbon quaternary center, a ring-closing alkene metathesis to give an 8-membered ring, and the use of a single enantiomer of p-menthane-3-carboxaldehyde to make two natural alkaloids of opposite configuration. Firstly, (+)-euphococcinine
Graphical Abstract
Figure 1: Homotropane (azabicyclononane) systems.
Figure 2: Alkaloids (−)-adaline (1), (+)-euphococcinine (2) and (+)-N-methyleuphococcinine (3).
Scheme 1: Synthetic strategies before 1995.
Scheme 2: Synthesis (±)-adaline (1) and (±)-euphococcinine (2). Reagents and conditions: i) 1. dihydropyran, ...
Scheme 3: Synthesis (+)-euphococcinine (2). Reagents and conditions: i) H2O2, SeO2 (cat), acetone, rt, 88%; i...
Scheme 4: Synthesis (+)-euphococcinine (2). Reagents and conditions: i) 2,4-bis(4-phenoxyphenyl)-1,3-dithia-2...
Scheme 5: Synthesis of (±)-euphococcinine precursor (±)-42. Reagents and conditions: i) Bu3SnH, AIBN, toluene...
Scheme 6: Synthesis of (−)-adaline (1). Reagents and conditions: i) LiH2NBH3, THF, 40 °C, 88%; ii) TPAP, NMO,...
Scheme 7: Synthesis of (−)-adaline (1) and (−)-euphococcinine (2). Reagents and conditions: i) 1. BuLi, t-BuO...
Scheme 8: Synthesis of (−)-adaline (1). Reagents and conditions: i) Ref. [52]; ii) Et3N, TBDMSOTf, CH2Cl2, 0 °C t...
Scheme 9: Synthesis of (+)-euphococcinine (2). Reagents and conditions: i) 1. Cp2ZrCl2,AlMe3, CH2Cl2; 2. p-me...
Scheme 10: Synthesis of (−)-adaline 1. Reagents and conditions: i) 1. CuBr.DMS, Et2O/DMS, -42 ºC; 2. 1-heptyne...
Scheme 11: Synthesis of (−)-euphococcinine (2) and (−)-adaline (1). Reagents and conditions: i) 102, KHMDS, Et2...
Scheme 12: Synthesis of N-methyleuphococcinine 3. Reagents and conditions: i) 108 (1.5 equiv), 3,5-di-F-C6H3B(...
Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates
- Hisham Qrareya,
- Lorenzo Meazza,
- Stefano Protti and
- Maurizio Fagnoni
Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250
- Truce–Smiles rearrangement in aryl sulfonamides and aryl phenylsulfonates [44][45][46] or the [3,3]-sigmatropic rearrangement of sulfonium salts arising from the reaction of aryl sulfoxides and phenols [47]. To overcome this problem, the use of a metal catalyst (mainly Ni) was mandatory as reported for
Graphical Abstract
Scheme 1: Synthesis of biarenes via a) photogenerated triplet aryl cations and aryl radicals (PC = photocatal...
Scheme 2: Metal-free photochemical synthesis of biaryls 2 and 4.
Figure 1: Emission spectrum of compound 1e (red) and of diethyl p-tert-butylphenyl phosphate (black) in metha...
Figure 2: Emission spectrum of compound 1h (red) and of diethyl p-cyanophenyl phosphate (black) in methanol.
Figure 3: Emission spectrum of compound 3a in methanol (black) and in a methanol/TFE 4:1 mixture (red).
Figure 4: Emission spectrum of 3c in MeOH (dotted line) and in the presence of increasing amounts of TFE (up ...
Scheme 3: Photoreactivity of aryl phosphates 1 and 3 in protic media.
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
- on a Diels–Alder cycloaddition, an intramolecular Mitsunobu reaction, a [3,3]-sigmatropic rearrangement, and a ring-closing metathesis. As an alternative to this approach, Clark et al. [86] efficiently performed a sequential Ru-catalyzed enyne metathesis in combination with a hydroboration, and an
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
- intermediate. This species then undergoes [3,3]-sigmatropic rearrangement, positioning the allylic unit in a regio- and stereospecific manner, along with rearomatization to afford the products 357–360 (Scheme 57) [107]. The borylfluoromethylation of acrylamides, acrylates, and heteroaromatic-substituted alkenes
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.
Why do thioureas and squaramides slow down the Ireland–Claisen rearrangement?
- Dominika Krištofíková,
- Juraj Filo,
- Mária Mečiarová and
- Radovan Šebesta
Beilstein J. Org. Chem. 2019, 15, 2948–2957, doi:10.3762/bjoc.15.290
- rearrangement; silyl ketene acetals; Introduction The Ireland–Claisen rearrangement is a reaction converting allyl esters to γ,δ-unsaturated carboxylic acids. Its key step is a [3,3]-sigmatropic rearrangement of a silyl ketene acetal, which is generated in situ by deprotonation of an allyl ester using a strong
Graphical Abstract
Scheme 1: Ireland–Claisen rearrangement of allyl esters 1a–c.
Scheme 2: Ireland–Claisen rearrangement of 1c mediated by tertiary amines.
Figure 1: Organocatalysts used in this study. Conditions: typical procedure: 1. Et3N (4.9 equiv), DCM, −60 °C...
Scheme 3: Solvent-free Ireland–Claisen rearrangement of cinnamyl esters.
Figure 2: ωB97X-D/6-31G* calculated uncatalyzed Ireland–Claisen rearrangement of 1c. Charges on allylic oxyge...
Figure 3: ωB97X-D/6-31G* calculated Schreiner thiourea (12)-catalyzed Ireland–Claisen rearrangement of 1c. Ch...
Figure 4: ωB97X-D/6-31G* calculated Ph-thiourea (top) and squaramide-catalyzed (bottom) Ireland–Claisen rearr...
Figure 5: a) Rate of product formation; b) reaction profile without catalyst determined by 1H NMR.
Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes
- Guillaume Ernouf,
- Jean-Louis Brayer,
- Christophe Meyer and
- Janine Cossy
Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29
- ]. In this review, we shall exclusively focus on alternative strategies that rely either on a [2,3]-sigmatropic rearrangement (Scheme 1, reaction 4) or a [3,3]-sigmatropic rearrangement of cyclopropenylcarbinol derivatives (Scheme 1, reaction 5). These transformations have emerged as useful tools over
- first highlighted by Marek et al. who investigated the transposition of cyclopropenylcarbinyl esters [33][34]. The [3,3]-sigmatropic rearrangement of acetate 10a took place during filtration on silica gel and afforded alkylidene(acetoxycyclopropane) 11a in 90% yield. The ease with which the
- nature of the rearrangement (Scheme 10) [33][34]. The acidic promotor may be simply assisting the dissociation of the C4–O bond in the transition state TS3 whilst an aromatic group (R1 = Ar) would contribute to the stabilization of a developing positive charge at C4. The [3,3]-sigmatropic rearrangement
Graphical Abstract
Scheme 1: Representative strategies for the formation of alkylidenecyclopropanes from cyclopropenes and scope...
Scheme 2: [2,3]-Sigmatropic rearrangement of phosphinites 2a–h.
Scheme 3: [2,3]-Sigmatropic rearrangement of a phosphinite derived from enantioenriched cyclopropenylcarbinol...
Scheme 4: Selective reduction of phosphine oxide (E)-3f.
Scheme 5: Attempted thermal [2,3]-sigmatropic rearrangement of phosphinite 6a.
Scheme 6: Computed activation barriers and free enthalpies.
Scheme 7: [2,3]-Sigmatropic rearrangement of phosphinites 6a–j.
Scheme 8: Proposed mechanism for the Lewis base-catalyzed rearrangement of phosphinites 6.
Scheme 9: [3,3]-Sigmatropic rearrangement of tertiary cyclopropenylcarbinyl acetates 10a–c.
Scheme 10: [3,3]-Sigmatropic rearrangement of secondary cyclopropenylcarbinyl esters 10d–h.
Scheme 11: [3,3]-Sigmatropic rearrangement of trichoroacetimidates 12a–i.
Scheme 12: Reaction of trichloroacetamide 13f with pyrrolidine.
Scheme 13: Catalytic hydrogenation of (arylmethylene)cyclopropropane 13f.
Scheme 14: Instability of trichloroacetimidates 21a–c derived from cyclopropenylcarbinols 20a–c.
Scheme 15: [3,3]-Sigmatropic rearrangement of cyanate 27 generated from cyclopropenylcarbinyl carbamate 26.
Scheme 16: Synthesis of alkylidene(aminocyclopropane) derivatives 30–37 from carbamate 26.
Scheme 17: Scope of the dehydration–[3,3]-sigmatropic rearrangement sequence of cyclopropenylcarbinyl carbamat...
Scheme 18: Formation of trifluoroacetamide 50 from carbamate 49.
Scheme 19: Formation of alkylidene[(N-trifluoroacetylamino)cyclopropanes] 51–54.
Scheme 20: Diastereoselective hydrogenation of alkylidenecyclopropane 51.
Scheme 21: Ireland–Claisen rearrangement of cyclopropenylcarbinyl glycolates 56a–l.
Scheme 22: Synthesis and Ireland–Claisen rearrangement of glycolate 61 possessing gem-diester substitution at ...
Scheme 23: Synthesis of alkylidene(gem-difluorocyclopropanes) 66a–h, and 66k–n from propargyl glycolates 64a–n....
Scheme 24: Ireland–Claisen rearrangement of N,N-diBoc glycinates 67a and 67b.
Scheme 25: Diastereoselective hydrogenation of alkylidenecyclopropanes 58a and 74.
Scheme 26: Synthesis of functionalized gem-difluorocyclopropanes 76 and 77 from alkylidenecyclopropane 66a.
Scheme 27: Access to oxa- and azabicyclic compounds 78–80.
Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres
- Myriam Drouin and
- Jean-François Paquin
Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262
- 11 was converted into the trichloroimidate, and heating in xylenes permitted a [3,3]-sigmatropic rearrangement. At this stage, the trichloroimidate was transformed into an NHBoc moiety. Deprotection of the alcohol followed by Jones oxidation gave the final dipeptide isostere 13. Taguchi and co
Graphical Abstract
Figure 1: Selected amide bond isosteres.
Figure 2: Monofluoroalkene as an amide bond isostere.
Scheme 1: Synthesis of Cbz-Gly-ψ[(Z)-CF=CH]-Gly using a HWE olefination by Sano and co-workers.
Scheme 2: Synthesis of Phth-Gly-ψ[CF=CH]-Gly using the Julia–Kocienski olefination by Lequeux and co-workers.
Scheme 3: Synthesis of Boc-Nva-ψ[(Z)-CF=CH]-Gly by Taguchi and co-workers.
Figure 3: Mutant tripeptide containing two different peptide bond isosteres.
Scheme 4: Chromium-mediated synthesis of Boc-Ser(PMB)-ψ[(Z)-CF=CH]-Gly-OMe by Konno and co-workers.
Scheme 5: Synthesis of Cbz-Gly-ψ[(E)-CF=C]-Pro by Sano and co-workers.
Scheme 6: Synthesis of Cbz-Gly-ψ[(Z)-CF=C]-Pro by Sano and co-workers.
Scheme 7: Stereoselective synthesis of Fmoc-Gly-ψ[(Z)-CF=CH]-Phe by Pannecoucke and co-workers.
Scheme 8: Ring-closure metathesis to prepare Gly-ψ[(E)-CF=CH]-Phg by Couve-Bonnaire and co-workers.
Scheme 9: Stereoselective synthesis of Fmoc-Gly-ψ[(Z)-CF=CH]-Phe by Dory and co-workers.
Scheme 10: Diastereoselective addition of Grignard reagents to sulfinylamines derived from α-fluoroenals by Pa...
Scheme 11: NHC-mediated synthesis of monofluoroalkenes by Otaka and co-workers.
Scheme 12: Stereoselective synthesis of Boc-Tyr-ψ[(Z)-CF=CH]-Gly by Altman and co-workers.
Scheme 13: Synthesis of the tripeptide Boc-Asp(OBn)-Pro-ψ[(Z)-CF=CH)-Val-CH2OH by Miller and co-workers.
Scheme 14: Copper-catalyzed synthesis of monofluoralkenes by Taguchi and co-workers.
Scheme 15: One-pot intramolecular redox reaction to access amide-type isosteres by Otaka and co-workers.
Scheme 16: Copper-mediated reduction, transmetalation and asymmetric alkylation by Fujii and co-workers.
Scheme 17: Synthesis of (E)-monofluoroalkene-based dipeptide isostere by Fujii and co-workers.
Scheme 18: Diastereoselective synthesis of MeOCO-Val-ψ[(Z)-CF=C]-Pro isostere by Chang and co-workers.
Scheme 19: Asymmetric synthesis of Fmoc-Ala-ψ[(Z)-CF=C]-Pro by Pannecoucke and co-workers.
Scheme 20: Synthesis of Fmoc-Val-ψ[(E)-CF=C]-Pro by Pannecoucke and co-workers.
Figure 4: BMS-790052 and its fluorinated analogue.
Figure 5: Bioactivities of pentapeptide analogues based on the relative maximum agonistic activity at 10 nM o...
Figure 6: Structures and affinities of the Leu-enkephalin and its fluorinated analogue. The affinity towards ...
Figure 7: Activation of the opioid receptor DOPr by Leu-enkephaline and a fluorinated analogue.
Study on the synthesis of the cyclopenta[f]indole core of raputindole A
- Nils Marsch,
- Mario Kock and
- Thomas Lindel
Beilstein J. Org. Chem. 2016, 12, 334–342, doi:10.3762/bjoc.12.36
- the catalyst solution through a pad of Celite prior to addition of the starting material to remove AgCl. In that way we reached an 81% yield of tricycle 50. The acetoxy group again formally underwent a 1,3-shift to the benzylic position, which may also be based on a [3,3]-sigmatropic rearrangement
Graphical Abstract
Figure 1: Bisindole alkaloid raputindole A (1) from the Amazonian tree Raputia simulans.
Scheme 1: Investigated synthetic precursors B–E of the cyclopenta[f]indole moiety (A) of raputindole A (1), a...
Scheme 2: 6-Iodoindole (2) serves twice as starting material towards indole-6-yl-substituted enone 8, obtaine...
Scheme 3: Assembly of 5-oxygenated bisindolylpentenones. DMB: 3,4-dimethoxybenzyl, DMFDMA: N,N-dimethylformal...
Scheme 4: Benzylic oxidation as side reaction of DMB removal.
Scheme 5: Hydroxyalkylation of N-protected indoles with β-cyclocitral and SnCl4-induced cyclization.
Scheme 6: Behavior of indolines after SnCl4-induced generation of allyl cations.
Scheme 7: Pt(II) and Au(I)-catalyzed cyclizations of propargylacetates 46 and 47 afforded cyclopenta[f]indoli...
Selected synthetic strategies to cyclophanes
- Sambasivarao Kotha,
- Mukesh E. Shirbhate and
- Gopalkrushna T. Waghule
Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142
Graphical Abstract
Figure 1: General representation of cyclophanes.
Figure 2: cyclophanes one or more with heteroatom.
Figure 3: Metathesis catalysts 12–17 and C–C coupling catalyst 18.
Figure 4: Natural products containing the cyclophane skeleton.
Figure 5: Turriane family of natural products.
Scheme 1: Synthesis of [3]ferrocenophanes through Mannich reaction. Reagents and conditions: (i) excess HNMe2...
Scheme 2: Synthesis of cyclophanes through Michael addition. Reagents and conditions: (i) xylylene dibromide,...
Scheme 3: Synthesis of normuscopyridine analogue 37 through an oxymercuration–oxidation strategy. Reagents an...
Scheme 4: Synthesis of tribenzocyclotriyne 39 through Castro–Stephens coupling reaction. Reagents and conditi...
Scheme 5: Synthesis of cyclophane 43 through Glaser–Eglinton coupling. Reagents and conditions: (i) 9,10-bis(...
Scheme 6: Synthesis of the macrocyclic C-glycosyl cyclophane through Glaser coupling. Reagents and conditions...
Scheme 7: Synthesis of cyclophane-containing complex 49 through Glaser–Eglinton coupling reaction. Reagents a...
Scheme 8: Synthesis of cyclophane 53 through Glaser–Eglinton coupling. Reagents and conditions: (i) K2CO3, ac...
Figure 6: Cyclophanes 54–56 that have been synthesized through Glaser–Eglinton coupling.
Figure 7: Synthesis of tetrasubstituted [2.2]paracyclophane 57 and chiral cyclophyne 58 through Eglinton coup...
Scheme 9: Synthesis of cyclophane through Glaser–Hay coupling reaction. Reagents and conditions: (i) CuCl2 (1...
Scheme 10: Synthesis of seco-C/D ring analogs of ergot alkaloids through intramolecular Heck reaction. Reagent...
Scheme 11: Synthesis of muscopyridine 73 via Kumada coupling. Reagents and conditions: (i) 72, THF, ether, 20 ...
Scheme 12: Synthesis of the cyclophane 79 via McMurry coupling. Reagents and conditions: (i) 75, decaline, ref...
Scheme 13: Synthesis of stilbenophane 81 via McMurry coupling. Reagents and conditions: (i) TiCl4, Zn, pyridin...
Scheme 14: Synthesis of stilbenophane 85 via McMurry coupling. Reagents and conditions: (i) NBS (2 equiv), ben...
Figure 8: List of cyclophanes prepared via McMurry coupling reaction as a key step.
Scheme 15: Synthesis of paracyclophane by cross coupling involving Pd(0) catalyst. Reagents and conditions: (i...
Scheme 16: Synthesis of the cyclophane 112 via the pinacol coupling and 113 by RCM. Reagents and conditions: (...
Scheme 17: Synthesis of cyclophane derivatives 122a–c via Sonogoshira coupling. Reagents and conditions: (i) C...
Scheme 18: Synthesis of cyclophane 130 via Suzuki–Miyaura reaction as a key step. Reagents and conditions: (i)...
Scheme 19: Synthesis of the mycocyclosin via Suzuki–Miyaura cross coupling. Reagents and conditions: (i) benzy...
Scheme 20: Synthesis of cyclophanes via Wurtz coupling reaction Reagents and conditions: (i) PhLi, Et2O, C6H6,...
Scheme 21: Synthesis of non-natural glycophanes using alkyne metathesis. Reagents and conditions: (i) G-I (12)...
Figure 9: Synthesis of cyclophanes via ring-closing alkyne metathesis.
Scheme 22: Synthesis of crownophanes by cross-enyne metathesis. Reagents and conditions: (i) G-II (13), 5 mol ...
Scheme 23: Synthesis of (−)-cylindrocyclophanes A (156) and (−)-cylindrocyclophanes F (155). Reagents and cond...
Scheme 24: Synthesis of cyclophane 159 derivatives via SM cross-coupling and RCM. Reagents and conditions: (i)...
Scheme 25: Sexithiophene synthesis via cross metathesis. Reagents and conditions: (i) 161, Pd(PPh3)4, K2CO3, T...
Scheme 26: Synthesis of pyrrole-based cyclophane using enyne metathesis. Reagents and conditions: (i) Se, chlo...
Scheme 27: Synthesis of macrocyclic derivatives by RCM. Reagents and conditions: (i) G-I/G-II, CH2Cl2, 0.005 M...
Scheme 28: Synthesis of enantiopure β-lactam-based dienyl bis(dihydrofuran) 179. Reagents and conditions: (i) ...
Scheme 29: Synthesis of a [1.1.6]metaparacyclophane derivative 183 via SM cross coupling. Reagents and conditi...
Scheme 30: Synthesis of a [1.1.6]metaparacyclophane derivative 190 via SM cross coupling. Reagents and conditi...
Scheme 31: Template-promoted synthesis of cyclophanes involving RCM. Reagents and conditions: (i) acenaphthene...
Scheme 32: Synthesis of [3.4]cyclophane derivatives 200 via SM cross coupling and RCM. Reagents and conditions...
Figure 10: Examples for cyclophanes synthesized by RCM.
Scheme 33: Synthesis of the longithorone C framework assisted by fluorinated auxiliaries. Reagents and conditi...
Scheme 34: Synthesis of the longithorone framework via RCM. Reagents and conditions: (i) 213, NaH, THF, rt, 10...
Scheme 35: Synthesis of floresolide B via RCM as a key step. Reagents and conditions: (i) G-II (13, 0.1 equiv)...
Scheme 36: Synthesis of normuscopyridine (223) by the RCM strategy. Reagents and condition: (i) Mg, THF, hexen...
Scheme 37: Synthesis of muscopyridine (73) via RCM. Reagents and conditions: (i) 225, NaH, THF, 0 °C to rt, 1....
Scheme 38: Synthesis of muscopyridine (73) via RCM strategy. Reagents and conditions: (i) NaH, n-BuLi, 5-bromo...
Scheme 39: Synthesis of pyridinophane derivatives 223 and 245. Reagents and conditions: (i) PhSO2Na, TBAB, CH3...
Scheme 40: Synthesis of metacyclophane derivatives 251 and 253. Reagents and conditions: (i) 240, NaH, THF, rt...
Scheme 41: Synthesis of normuscopyridine and its higher analogues. Reagents and conditions: (i) alkenyl bromid...
Scheme 42: Synthesis of fluorinated ferrocenophane 263 via a [2 + 2] cycloaddition. Reagents and conditions: (...
Scheme 43: Synthesis of [2.n]metacyclophanes 270 via a [2 + 2] cycloaddition. Reagents and conditions: (i) Ac2...
Scheme 44: Synthesis of metacyclophane 273 by a [2 + 2 + 2] co-trimerization. Reagents and conditions: (i) [Rh...
Scheme 45: Synthesis of paracyclophane 276 via a [2 + 2 + 2] cycloaddition reaction. Reagents and conditions: ...
Scheme 46: Synthesis of cyclophane 278 via a [2 + 2 + 2] cycloaddition reaction. Reagents and conditions: (i) ...
Scheme 47: Synthesis of cyclophane 280 via a [2 + 2 + 2] cycloaddition. Reagents and conditions: (i) [(Rh(cod)(...
Scheme 48: Synthesis of taxane framework by a [2 + 2 + 2] cycloaddition. Reagents and conditions: (i) Cp(CO)2 ...
Scheme 49: Synthesis of cyclophane 284 and 285 via a [2 + 2 + 2] cycloaddition reaction. Reagents and conditio...
Scheme 50: Synthesis of pyridinophanes 293a,b and 294a,b via a [2 + 2 + 2] cycloaddition. Reagents and conditi...
Scheme 51: Synthesis of pyridinophanes 296 and 297 via a [2 + 2 + 2] cycloaddition. Reagents and conditions: (...
Scheme 52: Synthesis of triazolophane by a 1,3-dipolar cycloaddition. Reagents and conditions: (i) propargyl b...
Scheme 53: Synthesis of glycotriazolophane 309 by a click reaction. Reagents and conditions: (i) LiOH, H2O, Me...
Figure 11: Cyclophanes 310 and 311 prepared via click chemistry.
Scheme 54: Synthesis of cyclophane via the Dötz benzannulation. Reagents and conditions: (i) THF, 100 °C, 12 h...
Scheme 55: Synthesis of [6,6]metacyclophane by a Dötz benzannulation. Reagents and conditions: (i) THF, 100 °C...
Scheme 56: Synthesis of cyclophanes by a Dötz benzannulation. Reagents and conditions: (i) THF, 65 °C, 3 h; (i...
Scheme 57: Synthesis of muscopyridine (73) via an intramolecular DA reaction of ketene. Reagents and condition...
Scheme 58: Synthesis of bis[10]paracyclophane 336 via Diels–Alder reaction. Reagents and conditions: (i) DMAD,...
Scheme 59: Synthesis of [8]paracyclophane via DA reaction. Reagents and conditions: (i) maleic anhydride, 3–5 ...
Scheme 60: Biomimetic synthesis of (−)-longithorone A. Reagents and conditions: (i) Me2AlCl, CH2Cl2, −20 °C, 7...
Scheme 61: Synthesis of sporolide B (349) via a [4 + 2] cycloaddition reaction. Reagents and conditions: (i) P...
Scheme 62: Synthesis of the framework of (+)-cavicularin (352) via a [4 + 2] cycloaddition. Reagents and condi...
Scheme 63: Synthesis of oxazole-containing cyclophane 354 via Beckmann rearrangement. Reagents and conditions:...
Scheme 64: Synthesis of cyclophanes 360a–c via benzidine rearrangement. Reagents and conditions: (i) 356a–d, K2...
Scheme 65: Synthesis of cyclophanes 365a–c via benzidine rearrangement. Reagents and conditions: (i) BocNHNH2,...
Scheme 66: Synthesis of metacyclophane 367 via Ciamician–Dennstedt rearrangement. Reagents and conditions: (i)...
Scheme 67: Synthesis of cyclophane by tandem Claisen rearrangement and RCM as key steps. Reagents and conditio...
Scheme 68: Synthesis of cyclophane derivative 380. Reagents and conditions: (i) K2CO3, CH3CN, allyl bromide, r...
Scheme 69: Synthesis of metacyclophane via Cope rearrangement. Reagents and conditions: (i) MeOH, NaBH4, rt, 1...
Scheme 70: Synthesis of cyclopropanophane via Favorskii rearrangement. Reagents and conditions: (i) Br2, CH2Cl2...
Scheme 71: Cyclophane 389 synthesis via photo-Fries rearrangement. Reagents and conditions: (i) DMAP, EDCl/CHCl...
Scheme 72: Synthesis of normuscopyridine (223) via Schmidt rearrangement. Reagents and conditions: (i) ethyl s...
Scheme 73: Synthesis of crownophanes by tandem Claisen rearrangement. Reagents and conditions: (i) diamine, Et3...
Scheme 74: Attempted synthesis of cyclophanes via tandem Claisen rearrangement and RCM. Reagents and condition...
Scheme 75: Synthesis of muscopyridine via alkylation with 2,6-dimethylpyridine anion. Reagents and conditions:...
Scheme 76: Synthesis of cyclophane via Friedel–Craft acylation. Reagents and conditions: (i) CS2, AlCl3, 7 d, ...
Scheme 77: Pyridinophane 418 synthesis via Friedel–Craft acylation. Reagents and conditions: (i) 416, AlCl3, CH...
Scheme 78: Cyclophane synthesis involving the Kotha–Schölkopf reagent 421. Reagents and conditions: (i) NBS, A...
Scheme 79: Cyclophane synthesis involving the Kotha–Schölkopf reagent 421. Reagents and conditions: (i) BEMP, ...
Scheme 80: Cyclophane synthesis by coupling with TosMIC. Reagents and conditions: (i) (a) ClCH2OCH3, TiCl4, CS2...
Scheme 81: Synthesis of diaza[32]cyclophanes and triaza[33]cyclophanes. Reagents and conditions: (i) DMF, NaH,...
Scheme 82: Synthesis of cyclophane 439 via acyloin condensation. Reagents and conditions: (i) Na, xylene, 75%;...
Scheme 83: Synthesis of multibridged binuclear cyclophane 442 by aldol condensation. Reagents and conditions: ...
Scheme 84: Synthesis of various macrolactones. Reagents and conditions: (i) iPr2EtN, DMF, 77–83%; (ii) TBDMSCl...
Scheme 85: Synthesis of muscone and muscopyridine via Yamaguchi esterification. Reagents and conditions: (i) 4...
Scheme 86: Synthesis of [5]metacyclophane via a double elimination reaction. Reagents and conditions: (i) LiBr...
Figure 12: Cyclophanes 466–472 synthesized via Hofmann elimination.
Scheme 87: Synthesis of cryptophane via Baylis–Hillman reaction. Reagents and conditions: (i) methyl acrylate,...
Scheme 88: Synthesis of cyclophane 479 via double Chichibabin reaction. Reagents and conditions: (i) excess 478...
Scheme 89: Synthesis of cyclophane 483 via double Chichibabin reaction. Reagents and conditions: (i) 481, OH−;...
Scheme 90: Synthesis of cyclopeptide via an intramolecular SNAr reaction. Reagents and conditions: (i) TBAF, T...
Scheme 91: Synthesis of muscopyridine (73) via C-zip ring enlargement reaction. Reagents and conditions: (i) H...
Figure 13: Mechanism of the formation of compound 494.
Scheme 92: Synthesis of indolophanetetraynes 501a,b using the Nicholas reaction as a key step. Reagents and co...
Scheme 93: Synthesis of cyclophane via radical cyclization. Reagents and conditions: (i) cyclododecanone, phen...
Scheme 94: Synthesis of (−)-cylindrocyclophanes A (156) and (−)-cylindrocyclophanes F (155). Reagents and cond...
Scheme 95: Cyclophane synthesis via Wittig reaction. Reagents and conditions: (i) LiOEt (2.1 equiv), THF, −78 ...
Figure 14: Representative examples of cyclophanes synthesized via Wittig reaction.
Scheme 96: Synthesis of the [6]paracyclophane via isomerization of Dewar benzene. Reagents and conditions: (i)...
Anionic sigmatropic-electrocyclic-Chugaev cascades: accessing 12-aryl-5-(methylthiocarbonylthio)tetracenes and a related anthra[2,3-b]thiophene
- Laurence Burroughs,
- John Ritchie,
- Mkhethwa Ngwenya,
- Dilfaraz Khan,
- William Lewis and
- Simon Woodward
Beilstein J. Org. Chem. 2015, 11, 273–279, doi:10.3762/bjoc.11.31
- , substituted phenyl, 2-thienyl) to ortho-C6H4(CHO)2 undergo cascades to tetracenes on simple admixture of LiHDMS, CS2 and MeI. Acene formation proceeds by [3,3]-sigmatropic rearrangement of xanthate anions followed by 6π electrocyclisations. The reactions are terminated by E2 or anionic Chugaev-type
- reaction components maximises the yield of 7a (Table 1, runs 3–6). These results very strongly suggest unprecedented anionic [3,3]-sigmatropic rearrangement starting from 1d; another addition to the body of evidence for the importance of charge upon sigmatropic rearrangements [25][26]. In the subsequent
Graphical Abstract
Scheme 1: Use of bis-allene intermediates 2 for rapid access to substituted tetracenes [14,16].
Scheme 2: Proposed access to aryl substituted 5-thiolatotetracene derivatives.
Scheme 3: Equilibration to meso species.
Scheme 4: Competing reaction pathways.
Scheme 5: Stacking motifs in 7a, d, f–h and j. Y = COSMe.
Synthesis of the B-seco limonoid core scaffold
- Hanna Bruss,
- Hannah Schuster,
- Rémi Martinez,
- Markus Kaiser,
- Andrey P. Antonchick and
- Herbert Waldmann
Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15
- framework of B-seco limonoid natural products by means of a [3,3]-sigmatropic rearrangement are described. Detailed model studies reveal, that an Ireland–Claisen rearrangement can be employed to construct the central C9–C10 bond thereby giving access to the B-seco limonoid scaffold. However, application of
- natural product classes to inspire the synthesis of probes and reagents for chemical biology and medicinal chemistry research, we aimed at the development of a synthetic strategy to get access to the B-seco limonoid scaffold by means of a [3,3]-sigmatropic rearrangement as key step enabling the formation
- alcohol 18 and Mitsunobu reaction installed the required stereochemistry at C14. The free C14 hydroxy group was masked with protecting groups (MOM and TIPS) of different size and chemical nature to examine the face-selectivity of the [3,3]-sigmatropic rearrangement. After selective desilylation, alcohols
Graphical Abstract
Figure 1: Structures of the 4,4,8-trimethyl-17-furanylsteroid core structure I and the representative B-seco ...
Scheme 1: Retrosynthetic analysis of the B-seco limonoid framework employing a [3,3]-sigmatropic rearrangemen...
Scheme 2: Retrosynthetic analysis of the B-seco limonoid scaffold employing a Claisen rearrangement as key st...
Scheme 3: Synthesis of alcohols 19, 20 and 22. Reagents and conditions: a) CSA, 2,3-butanedione, trimethyl or...
Scheme 4: Retrosynthetic analysis of the B-seco limonoid scaffold employing an Ireland–Claisen rearrangement ...
Scheme 5: Synthesis and Ireland–Claisen rearrangement of the allyl esters 27, 28, 29 and 30. Reagents and con...
Figure 2: Conformation of rearrangement precursor 30 and possible transition state involved in the Ireland–Cl...
Scheme 6: Synthesis of model C rings 40, 41 and 42. Reagents and conditions: a) TBDPSCl, DMAP, NEt3, CH2Cl2, ...
Scheme 7: β-Substituted allyl esters tested in the Ireland–Claisen and the Carroll rearrangement.
Scheme 8: Synthesis and Ireland–Claisen rearrangement of bicyclic allyl ester precursor 66. Reagents and cond...
Figure 3: Conformations of rearrangement precursors 66 and 77 and possible transition states involved in the ...
Scheme 9: Synthesis and Ireland–Claisen rearrangement of allyl ester 70. Reagents and conditions: a) DIPEA, M...
Scheme 10: Synthesis and Ireland–Claisen rearrangement of allyl ester 72. Reagents and conditions: a) TIPSOTf,...
Scheme 11: Synthesis of the C14-epi and C14/C9-epi B-seco limonoid scaffolds 78 and 79. Reagents and condition...
Scheme 12: Synthesis of fully functionalized A ring 87. Reagents and conditions: a) HO(CH2)2OH, THF, Pd/C, H2,...
Scheme 13: and Attempted Ireland–Claisen rearrangement of allyl ester 88. R1 = MOM, R2 = CO2H.
Scheme 14: Synthesis and attempted Ireland–Claisen rearrangement of allyl ester 93. Reagents and conditions: a...
Scheme 15: Allyl esters tested in the Ireland–Claisen rearrangement.
Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis
- Sebastian Krüger and
- Tanja Gaich
Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14
- cyclohepta[cd]oxindole core 32 proved the synthetic versatility of a [3,3]-sigmatropic rearrangement for direct C–C-bond formation at the C4 position of the indole nucleus, and thus provides experimental evidence for the biosynthetic proposal. Applications to natural product synthesis Fatty acid metabolites
Graphical Abstract
Scheme 1: Vogel’s first approach towards the divinylcyclopropane rearrangement [4] and characterization of cis-d...
Scheme 2: Transition states for the Cope rearrangement and the related DVCPR. Ts = transition state.
Scheme 3: Two possible mechanisms of trans-cis isomerizations of divinylcyclopropanes.
Scheme 4: Proposed biosynthesic pathway to ectocarpene (21), an inactive degradation product of a sexual pher...
Scheme 5: Proposed biosynthesis of occidenol (25) and related natural compounds.
Scheme 6: Gaich’s bioinspired system using the DVCPR to mimick the dimethylallyltryptophan synthase. DMAPP = ...
Scheme 7: Iguchi’s total synthesis of clavubicyclone, part 1.
Scheme 8: Iguchi’s total synthesis of clavubicyclone, part 2.
Scheme 9: Wender’s syntheses of the two pseudoguainanes confertin (50) and damsinic acid (51) and Pier’s appr...
Scheme 10: Overman’s total synthesis of scopadulcic acid B.
Scheme 11: Davies’ total syntheses of tremulenolide A and tremulenediol A.
Scheme 12: Davies formal [4 + 3] cycloaddition approach towards the formal synthesis of frondosin B.
Scheme 13: Davies and Sarpongs formal [4 + 3]-cycloaddition approach towards barekoxide (106) and barekol (107...
Scheme 14: Davies formal [4 + 3]-cycloaddition approach to 5-epi-vibsanin E (115) containing an intermediate c...
Scheme 15: Echavarren’s total synthesis of schisanwilsonene A (126) featuring an impressive gold-catalzed casc...
Scheme 16: Davies early example of a formal [4 + 3]-cycloaddition in alkaloids synthesis.
Scheme 17: Fukuyama’s total synthesis of gelsemine, part 1.
Scheme 18: Fukuyama’s total synthesis of gelsemine, featuring a divinylcyclopropane rearrangement, part 2.
Scheme 19: Kende’s total synthesis of isostemofoline, using a formal [4 + 3]-cycloaddition, including an inter...
Scheme 20: Danishefsky’s total synthesis of gelsemine, part 1.
Scheme 21: Danishefsky’s total synthesis of gelsemine, part 2.
Scheme 22: Fukuyama’s total synthesis of gelsemoxonine.
Scheme 23: Wender’s synthetic access to the core skeleton of tiglianes, daphnanes and ingenanes.
Scheme 24: Davies’ approach towards the core skeleton of CP-263,114 (212).
Scheme 25: Wood’s approach towards actinophyllic acid.
Scheme 26: Takeda’s approach towards the skeleton of the cyanthins, utilitizing the divinylcyclopropane rearra...
Scheme 27: Donaldson’s organoiron route towards the guianolide skeleton.
Scheme 28: Stoltz’s tandem Wolff/DVCPR rearrangement.
Scheme 29: Stephenson’s tandem photocatalysis/arylvinylcyclopropane rearrangement.
Scheme 30: Padwa’s rhodium cascade involving a DVCPR.
Scheme 31: Matsubara’s version of a DVCPR.
Scheme 32: Toste’s tandem gold-catalyzed Claisen-rearrangement/DVCPR.
Scheme 33: Ruthenium- and gold-catalyzed versions of tandem reactions involving a DVCPR.
Scheme 34: Tungsten, platinum and gold catalysed cycloisomerizations leading to a DVCPR.
Scheme 35: Reisman’s total synthesis of salvileucalin B, featuring an (undesired) vinylcyclopropyl carbaldehyd...
Scheme 36: Studies on the divinylepoxide rearrangement.
Scheme 37: Studies on the vinylcyclopropanecarbonyl rearrangement.
Scheme 38: Nitrogen-substituted variants of the divinylcyclopropane rearrangement.
An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles
- Marcus Baumann and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265
Graphical Abstract
Scheme 1: Scaled industrial processes for the synthesis of simple pyridines.
Scheme 2: Synthesis of nicotinic acid from 2-methyl-5-ethylpyridine (1.11).
Scheme 3: Synthesis of 3-picoline and nicotinic acid.
Scheme 4: Synthesis of 3-picoline from 2-methylglutarodinitrile 1.19.
Scheme 5: Picoline-based synthesis of clarinex (no yields reported).
Scheme 6: Mode of action of proton-pump inhibitors and structures of the API’s.
Scheme 7: Hantzsch-like route towards the pyridine rings in common proton pump inhibitors.
Figure 1: Structures of rosiglitazone (1.40) and pioglitazone (1.41).
Scheme 8: Synthesis of rosiglitazone.
Scheme 9: Syntheses of 2-pyridones.
Scheme 10: Synthesis and mechanism of 2-pyrone from malic acid.
Scheme 11: Polymer-assisted synthesis of rosiglitazone.
Scheme 12: Synthesis of pioglitazone.
Scheme 13: Meerwein arylation reaction towards pioglitazone.
Scheme 14: Route towards pioglitazone utilising tyrosine.
Scheme 15: Route towards pioglitazone via Darzens ester formation.
Scheme 16: Syntheses of the thiazolidinedione moiety.
Scheme 17: Synthesis of etoricoxib utilising Negishi and Stille cross-coupling reactions.
Scheme 18: Synthesis of etoricoxib via vinamidinium condensation.
Figure 2: Structures of nalidixic acid, levofloxacin and moxifloxacin.
Scheme 19: Synthesis of moxifloxacin.
Scheme 20: Synthesis of (S,S)-2,8-diazabicyclo[4.3.0]nonane 1.105.
Scheme 21: Synthesis of levofloxacin.
Scheme 22: Alternative approach to the levofloxacin core 1.125.
Figure 3: Structures of nifedipine, amlodipine and clevidipine.
Scheme 23: Mg3N2-mediated synthesis of nifedipine.
Scheme 24: Synthesis of rac-amlodipine as besylate salt.
Scheme 25: Aza Diels–Alder approach towards amlodipine.
Scheme 26: Routes towards clevidipine.
Figure 4: Examples of piperidine containing drugs.
Figure 5: Discovery of tiagabine based on early leads.
Scheme 27: Synthetic sequences to tiagabine.
Figure 6: Structures of solifenacin (2.57) and muscarine (2.58).
Scheme 28: Enantioselective synthesis of solifenacin.
Figure 7: Structures of DPP-4 inhibitors of the gliptin-type.
Scheme 29: Formation of inactive diketopiperazines from cis-rotameric precursors.
Figure 8: Co-crystal structure of carmegliptin bound in the human DPP-4 active site (PDB 3kwf).
Scheme 30: Improved route to carmegliptin.
Figure 9: Structures of lamivudine and zidovudine.
Scheme 31: Typical routes accessing uracil, thymine and cytosine.
Scheme 32: Coupling between pyrimidones and riboses via the Vorbrüggen nucleosidation.
Scheme 33: Synthesis of lamivudine.
Scheme 34: Synthesis of raltegravir.
Scheme 35: Mechanistic studies on the formation of 3.22.
Figure 10: Structures of selected pyrimidine containing drugs.
Scheme 36: General preparation of pyrimidines and dihydropyrimidones.
Scheme 37: Synthesis of imatinib.
Scheme 38: Flow synthesis of imatinib.
Scheme 39: Syntheses of erlotinib.
Scheme 40: Synthesis of erlotinib proceeding via Dimroth rearrangement.
Scheme 41: Synthesis of lapatinib.
Scheme 42: Synthesis of rosuvastatin.
Scheme 43: Alternative preparation of the key aldehyde towards rosuvastatin.
Figure 11: Structure comparison between nicotinic acetylcholine receptor agonists.
Scheme 44: Syntheses of varenicline and its key building block 4.5.
Scheme 45: Synthetic access to eszopiclone and brimonidine via quinoxaline intermediates.
Figure 12: Bortezomib bound in an active site of the yeast 20S proteasome ([114], pdb 2F16).
Scheme 46: Asymmetric synthesis of bortezomib.
Figure 13: Structures of some prominent piperazine containing drugs.
Figure 14: Structural comparison between the core of aplaviroc (4.35) and a type-1 β-turn (4.36).
Scheme 47: Examplary synthesis of an aplaviroc analogue via the Ugi-MCR.
Scheme 48: Syntheses of azelastine (5.1).
Figure 15: Structures of captopril, enalapril and cilazapril.
Scheme 49: Synthesis of cilazapril.
Figure 16: Structures of lamotrigine, ceftriaxone and azapropazone.
Scheme 50: Synthesis of lamotrigine.
Scheme 51: Alternative synthesis of lamotrigine (no yields reported).
Figure 17: Structural comparison between imiquimod and the related adenosine nucleoside.
Scheme 52: Conventional synthesis of imiquimod (no yields reported).
Scheme 53: Synthesis of imiquimod.
Scheme 54: Synthesis of imiquimod via tetrazole formation (not all yields reported).
Figure 18: Structures of various anti HIV-medications.
Scheme 55: Synthesis of abacavir.
Figure 19: Structures of diazepam compared to modern replacements.
Scheme 56: Synthesis of ocinaplon.
Scheme 57: Access to zaleplon and indiplon.
Scheme 58: Different routes towards the required N-methylpyrazole 6.65 of sildenafil.
Scheme 59: Polymer-supported reagents in the synthesis of key aminopyrazole 6.72.
Scheme 60: Early synthetic route to sildenafil.
Scheme 61: Convergent preparations of sildenafil.
Figure 20: Comparison of the structures of sildenafil, tadalafil and vardenafil.
Scheme 62: Short route to imidazotriazinones.
Scheme 63: Alternative route towards vardenafils core imidazotriazinone (6.95).
Scheme 64: Bayer’s approach to the vardenafil core.
Scheme 65: Large scale synthesis of vardenafil.
Scheme 66: Mode of action of temozolomide (6.105) as methylating agent.
Scheme 67: Different routes to temozolomide.
Scheme 68: Safer route towards temozolomide.
Figure 21: Some unreported heterocyclic scaffolds in top market drugs.
Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene
- Peter A. Wade,
- Alma Pipic,
- Matthias Zeller and
- Panagiota Tsetsakos
Beilstein J. Org. Chem. 2013, 9, 2137–2146, doi:10.3762/bjoc.9.251
- intermediate. The initially isolated nitronic ester cycloadducts underwent tin(IV)-catalyzed interconversion, presumably via zwitterion intermediates. Cycloadducts derived from the reaction at the less substituted double bond of (E)-3-methyl-1,3-pentadiene underwent a [3,3]-sigmatropic rearrangement on heating
- initial assessment of substituent effects on the rearrangement process is presented. Keywords: cycloaddition; diene; nitro; nitronate; rearrangement; Introduction We have previously reported examples of a general new [3,3]-sigmatropic rearrangement, the conversion of O-allyl nitronic esters (nitronates
- )-catalyzed [3,3]-sigmatropic rearrangement of nitronic ester 5 affords nitro compound 16 (vide infra). The rapid interconversion of nitronic esters 2 and 3 likely reflects the greater ease of rotation for the cyclo zwitterion 17. Here bond breaking and reformation is at a secondary rather than tertiary
Graphical Abstract
Scheme 1: Reaction intermediates, resulting products, and model cations.
Scheme 2: Sn(IV)-catalyzed isomerization of nitronic esters.
Scheme 3: Thermal rearrangement of nitronic esters 2 and 3.
Scheme 4: Thermal rearrangement of nitronic esters 21a, 21b and 22b.
Scheme 5: Thermal reactions of nitronic esters 5, 7, and 26a–d.
Scheme 6: General transition state for the [3,3]-sigmatropic rearrangement of O-allyl nitronic esters.
Scheme 7: Thermal rearrangement of nitronic ester 30.
Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements
- Jungho Jun,
- Hyu-Suk Yeom,
- Jun-Hyun An and
- Seunghoon Shin
Beilstein J. Org. Chem. 2013, 9, 1724–1729, doi:10.3762/bjoc.9.198
- polarization of alkynes both by a gold catalyst and a sulfonyl substituent resulted in an efficient intermolecular tandem carboalkoxylation. Reactions of linear allyl ethers are consistent with the [3,3]-sigmatropic rearrangement mechanism, while those of branched allyl ethers provided [3,3]- and [1,3
- ]-rearrangement products through the formation of a tight ion–dipole pair. Keywords: gold catalysis; intermolecular coupling; [1,3]-rearrangement; [3,3]-sigmatropic rearrangement; sulfonylacetylene; Introduction Homogeneous gold catalysis has been established during the last decade as a prominent tool in
- undergo intermolecular alkoxylation-[3,3]-sigmatropic rearrangement under Ag(I) or Au(I) catalysis [7][8], allyl ethers that are less nucleophilic due to steric reasons react more slowly and have not been known to undergo similar reactions until recently. In our previous work [9], it was shown that ester
Graphical Abstract
Figure 1: Donor- and acceptor-substituted alkynes for Au-catalyzed intermolecular reactions.
Scheme 1: Proposed mechanism of the [3,3]- and [1,3]-rearrangement.
Scheme 2: Experiments to investigate the reaction mechanism.
Efficient, highly diastereoselective MS 4 Å-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization
- Naseem Ahmed and
- Naveen Kumar Konduru
Beilstein J. Org. Chem. 2012, 8, 177–185, doi:10.3762/bjoc.8.19
- tetrahydropyrans. After 22 h stirring more side-products than the desired product were observed. This might be due to the formation of an oxo-carbenium intermediate, which further reacted in a [3,3]sigmatropic rearrangement to give another oxo-carbenium ion (Scheme 1). To optimize the reaction yield, we varied the
- conditions (Table 1, entry 9 vs entry 10). The significant improvements in product yields, reaction time and/or diastereoselectivity might be due to the prevention of the [3,3]sigmatropic rearrangement along with the dehydrating activity of MS 4 Å. In addition, we studied the stoichiometric ratio of MS 4 Å
- unsymmetrical tetrahydropyran derivatives in an economical manner. Moreover, it was observed that MS 4 Å might have a vital part in controlling the reversibility of the [3,3]sigmatropic rearrangement. Furthermore, cleavage of the 4-tosyl group under mild conditions afforded 4-hydroxytetrahydropyrans in high
Graphical Abstract
Figure 1: Tetrahydropyran ring containing natural products.
Scheme 1: Plausible side products mechanism.
Scheme 2: Plausible reaction mechanism via Prins cyclization.
Figure 2: Schematic NOE diagram of compound 3b.
Scheme 3: Deprotection of the hydroxy group.
Synthetic applications of gold-catalyzed ring expansions
- David Garayalde and
- Cristina Nevado
Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87
- into the angular triquinane ventricosene in six steps (Scheme 23). 6 Ring expansions involving propargyl acyloxy rearrangements Propargyl carboxylates 80 can be π-activated by gold towards 1,2-acyloxy migration and/or [3,3]-sigmatropic rearrangement. Two different, but mechanistically related
- , intermediates characterize these competitive processes, i.e., 1,2-migration via metal "carbenoid" 81 formation and [3,3]-sigmatropic rearrangement via allenyl acetate 82 as an intermediate (Scheme 24) [5][56][57]. In 2008, Toste and co-workers reported a gold(I)-catalyzed cycloisomerization of cis-pivaloyloxy
Graphical Abstract
Scheme 1: Transition metal promoted rearrangements of bicyclo[1.1.0]butanes.
Scheme 2: Gold-catalyzed rearrangements of strained rings.
Scheme 3: Gold-catalyzed ring expansions of cyclopropanols and cyclobutanols.
Scheme 4: Mechanism of the cycloisomerization of alkynyl cyclopropanols and cyclobutanols.
Scheme 5: Proposed mechanism for the Au-catalyzed isomerization of alkynyl cyclobutanols.
Scheme 6: Gold-catalyzed cycloisomerization of 1-allenylcyclopropanols.
Scheme 7: Gold-catalyzed cycloisomerization of cyclopropylmethanols.
Scheme 8: Gold-catalyzed cycloisomerization of aryl alkyl epoxides.
Scheme 9: Gold-catalyzed synthesis of furans.
Scheme 10: Transformations of alkynyl oxiranes.
Scheme 11: Transformations of alkynyl oxiranes into ketals.
Scheme 12: Gold-catalyzed cycloisomerization of cyclopropyl alkynes.
Scheme 13: Gold-catalyzed synthesis of substituted furans.
Scheme 14: Proposed mechanism for the isomerization of alkynyl cyclopropyl ketones.
Scheme 15: Cycloisomerization of cyclobutylazides.
Scheme 16: Cycloisomerization of alkynyl aziridines.
Scheme 17: Gold-catalyzed synthesis of disubstituted cyclohexadienes.
Scheme 18: Gold-catalyzed synthesis of indenes.
Scheme 19: Gold-catalyzed [n + m] annulation processes.
Scheme 20: Gold-catalyzed generation of 1,4-dipoles.
Scheme 21: Gold-catalyzed synthesis of repraesentin F.
Scheme 22: Gold-catalyzed ring expansion of cyclopropyl 1,6-enynes.
Scheme 23: Gold-catalyzed synthesis of ventricos-7(13)-ene.
Scheme 24: 1,2- vs 1,3-Carboxylate migration.
Scheme 25: Gold-catalyzed cycloisomerization of vinyl alkynyl cyclopropanes.
Scheme 26: Proposed mechanism for the cycloisomerization of vinyl alkynyl cyclopropanes.
Scheme 27: Gold-catalyzed 1,2-acyloxy rearrangement/cyclopropanation/cycloisomerization cascades.
Scheme 28: Formal total synthesis of frondosin A.
Scheme 29: Gold-catalyzed rearrangement/cycloisomerization of cyclopropyl propargyl acetates.
Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B
- Silke Dubberke,
- Muhammad Abbas and
- Bernhard Westermann
Beilstein J. Org. Chem. 2011, 7, 421–425, doi:10.3762/bjoc.7.54
- steric interference was believed to be a major obstacle of this process, this factor turned out to be unimportant. It is assumed, that the transition state during [3,3]-sigmatropic rearrangement is as shown in Scheme 3 [23][24], where the hydroxyl group is fixed in a pseudo-axial orientation, any other
Graphical Abstract
Scheme 1: PLE (pig liver esterase)-catalyzed saponification of β-ketoesters 1.
Figure 1: (9E)- and (9Z)-trisporic acid B.
Scheme 2: Synthesis and PLE-catalyzed saponification of β-ketoester 1c.
Scheme 3: Synthesis of key building block (+)-7.
Recent advances in carbocupration of α-heterosubstituted alkynes
- Ahmad Basheer and
- Ilan Marek
Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77
- undergoes a subsequent thermal [3,3]-sigmatropic rearrangement to give the corresponding nitrile 27. The presence of the organomagnesium group on 26 is essential for the rearrangement to proceed in good yield (Scheme 12). The silylcupration of N-1-alkynylsulfonylamides 28 led to the desired vinylsilane
Graphical Abstract
Scheme 1: General scheme for the carbocupration reaction.
Scheme 2: Regioselectivity in the carbocupration reaction.
Scheme 3: Carbocupration of α-alkoxyalkynes.
Scheme 4: Carbocupration of substituted α-alkoxyalkynes.
Scheme 5: Formation of the branched isomer.
Scheme 6: Formation of the linear isomer.
Scheme 7: Carbocupration of O-alkynyl carbamates.
Scheme 8: Carbocupration of ynamines.
Scheme 9: Carbocupration of ynamide.
Scheme 10: Formation of aldol products possessing stereogenic quaternary carbon centers.
Scheme 11: Carbocupration of alkynyl sulfonamide.
Scheme 12: Tandem carbocupration-sigmatropic rearrangement.
Scheme 13: Silylcupration of alkynyl sulfonamides.
Scheme 14: Carbocupration of P-substituted alkynes.
Scheme 15: Carbocupration of alkynylphosphonates.
Scheme 16: Carbocupration of thioalkynes.
Scheme 17: Tandem carbocupration-1,2-metalate rearrangement.
Scheme 18: Carbocupration with functionalized organocopper species.
Scheme 19: Carbocupration of alkynyl sulfoxides.
Scheme 20: Carbocupration of alkynyl sulfones.
Scheme 21: Carbocupration of alkynyl sulfoximines.
Scheme 22: Carbocupration of alkynylsilanes.
Scheme 23: Carbocupration of functionalized alkynylsilanes.
Scheme 24: Silyl- and stannyl cupration of silyl- and stannylalkynes.
A thermally-induced, tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition approach to carbocyclic spirooxindoles
- Kay M. Brummond and
- Joshua M. Osbourn
Beilstein J. Org. Chem. 2010, 6, No. 33, doi:10.3762/bjoc.6.33
- observed, but are likely intermediates of an infrequently encountered thermal [3,3]-sigmatropic rearrangement of a propargylic acetate. Keywords: allene; propargylic acetate; spirooxindole; thermal [2 + 2] cycloaddition; thermal [3,3]-sigmatropic rearrangement; vinylidene indolin-2-one; Introduction
- 5 could be obtained by way of a thermal [3,3]-sigmatropic rearrangement of the propargylic acetate 6 to give compound 5 where R2 = OAc (Figure 2) [27]. Preparation of propargylic acetate 9a was accomplished by the addition of the lithium acetylide of 8 to N-methyl isatin (7) followed by acetylation
- allenyl acetate in intermediate 11 which in turn arises from the thermal [3,3]-sigmatropic rearrangement of 9a (Figure 3). We have briefly investigated the scope and limitations of this tandem cycloaddition reaction by varying the protecting group on the oxindole nitrogen, altering the substitution on the
Graphical Abstract
Figure 1: Heterocyclic and carbocyclic spirooxindoles.
Scheme 1: A thermal [2 + 2] cycloaddition reaction.
Figure 2: Access to vinylidene indolin-2-ones.
Scheme 2: A tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition.
Figure 3: A tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition.
