Synthesis of tryptophan derivatives via a palladium-catalyzed N-heteroannulation

Dacko, Christopher A.; Akhmedov, Novruz G.; Söderberg, Björn C.G.

doi:10.1016/j.tetasy.2008.10.032

Cited by 22 publications

(9 citation statements)

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“…In continuation of our synthetic work, [23] we now report unequivocally assigned NMR data (chemical shifts and coupling constants) for bis-lactim ether 1 and (S)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine-substituted indoles 2-10 (Scheme 1) along with their conformational preference in solution based on gradient-selected 1D NOESY double pulsed field gradient spin echo nuclear overhauser effect (DPFGSE NOE) and 2D NOESY spectra. Both experiments provide information about spatial proximity (dipolar interaction) between hydrogens and thus establishing the conformation.…”

Section: Introductionmentioning

confidence: 71%

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Complete analysis of the ¹H and ¹³C NMR spectra of diastereomeric mixtures of (R,S‐ and S,S‐)‐3,6‐dimethoxy‐2,5‐dihydropyrazine‐substituted indoles and their conformational preference in solution

Akhmedov

Dacko

Güven

et al. 2009

Magnetic Reson in Chemistry

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Complete analysis of the (1)H and (13)C NMR spectra obtained with and without a chemical shift reagent (Eu(fod)(3)), of bis-lactim ether 1 (Schöllkopf auxiliary) and monosubstituted 3- or 2-{(2R,5S or 2S,5S)-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazin-2-yl]methyl}-1H-indoles is presented using gradient-selected one-dimensional (1D) and two-dimensional NMR techniques, such as 1D TOCSY, 1D NOESY (DPFGSE NOE), gCOSY, NOESY, ROESY gHETCOR, gHSQC and gHMBC. The contour plot of the gCOSY spectrum of 1-10 revealed cross peaks arising from the five-bond coupling between the H2 and H5 resonances of the dihydropyrazine ring for syn- ((5)J(H2, H5) = 4-5.7 Hz) and for anti-isomers ((5)J(H2, H5) = 3.4-3.8 Hz). The magnitude of the coupling constant was utilized to distinguish between the syn- and the anti-isomers (diastereomers). The precise values of (n)J(HH) (n = 3, 4, 5, 6) coupling constants for the indole and 2,5-dihydropyrazine moieties deduced from the calculated NMR spectra were supported by 1D TOCSY and gCOSY experiments and gauge invariant atomic orbital (GIAO) calculations. The magnitude of the coupling constants ((5)J(H2, H5)) indicates that the dihydropyrazine ring exists in a boat conformation. In both isomers, the indole group adopts a 'folded' conformation in which one diastereotopic face is effectively shielded by the aromatic benzene ring of the indole. This is supported by gradient-selected 1D NOESY and 2D NOESY experiments. Theoretical calculations of the conformation were performed to support the through-space shielding effect of the aromatic indole moiety based on the DFT/GIAO calculated (1)H NMR data (chemical shifts and coupling constants) for 2-syn- and 2-anti-diastereomers in CDCl(3).

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Section: Introductionmentioning

confidence: 71%

“…Compounds 1-10 were synthesized using two sequential palladium-catalyzed reactions, a Stille cross-coupling and a reductive N-heteroannulation. [23] The numbering of carbon atoms is shown in Scheme 1. The methylene protons at C-2 are denoted as 2-CH A H B .…”

Section: Methodsmentioning

confidence: 99%

Complete analysis of the ¹H and ¹³C NMR spectra of diastereomeric mixtures of (R,S‐ and S,S‐)‐3,6‐dimethoxy‐2,5‐dihydropyrazine‐substituted indoles and their conformational preference in solution

Akhmedov

Dacko

Güven

et al. 2009

Magnetic Reson in Chemistry

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“…lines and δ-oxo amino acids, 16 cyclisation of amino acid derived nitrostyrenes, 17 or Negishi coupling of 3-iodoindoles with β-metallated enantioenriched amino acid derivatives. 18 The stereogenic α-centre can be introduced under auxiliary control, 19 or by asymmetric hydrogenation of βunsaturated amino acid derivatives.…”

Section: Syn Lettmentioning

confidence: 99%

A Straightforward Protocol for the Synthesis of Functionalized Tryptophan Peptides via Stille Coupling, Azidation and Photoinduced Nitrene Insertion

Junk

Kazmaier

2016

Synlett

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All air-or moisture-sensitive reactions were carried out in dried glassware (> 100 °C) under an atmosphere of argon. THF was distilled over Na/benzophenone prior to use. Dichloromethane (DCM), MeCN and DMF (anhydrous) were purchased from Sigma-Aldrich. EtOAc and petroleum ether (PE) were distilled prior to use. Reactions were monitored by analytical TLC, which was performed on silica gel on TLC PET-foils by Sigma-Aldrich. Visualization was accomplished with UV-light (254 nm), KMnO 4 solution or an iodine chamber. Rotary evaporation was conducted at 40 °C. The products were purified by flash chromatography on silica gel columns (Macherey-Nagel 60, 0.063-0.2 mm) or by automated flash chromatography (Grace Reveleris®, Teledyne Isco RediSep R f silica cartridges). Mixtures of EtOAc and PE were generally used as eluents. Melting points were determined with a melting point apparatus IA 9100 by Electrothermal and are uncorrected. 1 H, 13 C, 119 Sn and 19 F NMR spectra were recorded with a Bruker AV II 400 [400 MHz (1 H), 100 MHz (13 C), 149 MHz (119 Sn), 376 MHz (19 F)] or a Bruker AV 500 [500 MHz, (1 H), 125 MHz (13 C)] spectrometer in CDCl 3 (+0.01% Si(CH 3) 4) unless otherwise specified. NMR spectra were evaluated using iNMR (Version 5.4.4). Chemical shifts are reported in ppm relative to Si(CH 3) 4 and CHCl 3 was used as the internal standard [δ(1 H) = 7.26 ppm, δ(13 C) = 77.0 ppm]. Multiplicities are reported as bs (broad signal), s (singlet), d (doublet), t (triplet), q (quartet) and m (multiplet). High resolution mass spectra were recorded with a Finnigan MAT 95 spectrometer using the CI technique. Optical rotations were measured with a Perkin-Elmer polarimeter (model 341) in a thermostated (20 °C ± 1 °C) cuvette. The radiation source used was a sodium vapor lamp (λ = 589 nm). The concentrations are given in g/100 ml. Diastereomeric ratios were determined by HPLC using an instrument from Merck-Hitachi (model LaChrom D-7000). The chiral stationary phase used was Repropsil 100 Chiral-NR 8 µm (250 × 4.6 mm) from Trentec. The evaluation was conducted using Multi-HSM-Manager (Merck). Photochemical experiments were conducted with a UV-LED [UV-LED SMART by Opsytec Dr. Gröbel GmbH (max. irradiance >25 W/cm 2 , λ = 365 nm, beam profile: standard, distance from reaction mixture: ca. 5 cm)]. 2. Experimental Section General procedures (GP) 2.1. General procedure 1: Stille cross coupling An oven dried Schlenk tube was charged with LiCl (2.0 equiv) and heated with a heat gun under vacuum (< 0.1 mbar). After cooling to room temperature CuI (2.0 equiv), (substituted) o-iodoaniline (1.0 equiv) and Pd(PPh 3) 4 (5 mol%) were added and the flask was evacuated and refilled with Ar three times. DMF (10 mL/mmol), which was previously degassed by bubbling with Ar, and the organotin compound (1.2 equiv) was added and the mixture was heated to 80 °C for 18 h. After reaching full conversion (TLC) the mixture was diluted with EtOAc and 1 M KF-solution (5 mL/mmol) was added. Upon vigorous shaking (in the Schlenk tube) a colorless precipitate...

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“…Söderberg's method has been successfully applied to the synthesis of a number of indole analogs including tryptophan derivatives, 14 bicyclic heteroaromatics, 15 carbazole alkaloids, 16 mushroom metabolites, 17 and various natural products. [18][19][20][21][22][23][24][25] Through a detailed optimization study of the reaction conditions, it was observed that the Pd(dba)2-dppp-1,10-phenanthroline system using DMF as solvent at 120 °C under 6 atm of carbon monoxide (Scheme 3) was highly applicable to late stage indolization during many natural products syntheses.…”

Section: Scheme 2: Watanabe and Söderberg Reductive Heterocyclizationmentioning

confidence: 99%

Syntheses of azepinoindole alkaloids cimitrypazepine, fargesine and hyrtioreticulins C & D

Ghimire¹

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Syntheses of azepinoindole alkaloids cimitrypazepine, fargesine and hyrtioreticulins C & D Ganesh Ghimire The Watanabe-Cenini-Söderberg reductive N-heterocyclization has emerged as a powerful tool for the synthesis of a variety of functionalized indoles. Söderberg's elaboration of this methodology has been utilized as a late-stage cyclization protocol for the synthesis of azepinoindole alkaloids, a class of natural products characterized by an azepane skeleton fused with an indole ring. Short syntheses of the naturally occurring azepino[5,4,3-cd]indole alkaloids, cimitrypazepine, fargesine, and the diastereomeric hyrtioreticulins C & D have been completed starting from commercially available tetra-substituted benzene derivatives. The key azepinoindole core in each case was assembled via an intramolecular Mizoroki-Heck reaction followed by a Watanabe-Cenini-Söderberg reductive N-heterocyclization. Synthesis of aurantioclavine using a similar strategy is currently underway.

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Synthesis of tryptophan derivatives via a palladium-catalyzed N-heteroannulation

Cited by 22 publications

References 25 publications

Complete analysis of the ¹H and ¹³C NMR spectra of diastereomeric mixtures of (R,S‐ and S,S‐)‐3,6‐dimethoxy‐2,5‐dihydropyrazine‐substituted indoles and their conformational preference in solution

Complete analysis of the ¹H and ¹³C NMR spectra of diastereomeric mixtures of (R,S‐ and S,S‐)‐3,6‐dimethoxy‐2,5‐dihydropyrazine‐substituted indoles and their conformational preference in solution

A Straightforward Protocol for the Synthesis of Functionalized Tryptophan Peptides via Stille Coupling, Azidation and Photoinduced Nitrene Insertion

Syntheses of azepinoindole alkaloids cimitrypazepine, fargesine and hyrtioreticulins C & D

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Synthesis of tryptophan derivatives via a palladium-catalyzed N-heteroannulation

Cited by 22 publications

References 25 publications

Complete analysis of the 1H and 13C NMR spectra of diastereomeric mixtures of (R,S‐ and S,S‐)‐3,6‐dimethoxy‐2,5‐dihydropyrazine‐substituted indoles and their conformational preference in solution

Complete analysis of the 1H and 13C NMR spectra of diastereomeric mixtures of (R,S‐ and S,S‐)‐3,6‐dimethoxy‐2,5‐dihydropyrazine‐substituted indoles and their conformational preference in solution

A Straightforward Protocol for the Synthesis of Functionalized Tryptophan Peptides via Stille Coupling, Azidation and Photoinduced Nitrene Insertion

Syntheses of azepinoindole alkaloids cimitrypazepine, fargesine and hyrtioreticulins C & D

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Complete analysis of the ¹H and ¹³C NMR spectra of diastereomeric mixtures of (R,S‐ and S,S‐)‐3,6‐dimethoxy‐2,5‐dihydropyrazine‐substituted indoles and their conformational preference in solution

Complete analysis of the ¹H and ¹³C NMR spectra of diastereomeric mixtures of (R,S‐ and S,S‐)‐3,6‐dimethoxy‐2,5‐dihydropyrazine‐substituted indoles and their conformational preference in solution