- Total Synthesis of (+)-Erogorgiaene and the Pseudopterosin A?F Aglycone via Enantioselective Cobalt-Catalyzed Hydrovinylation
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Due to their pronounced bioactivity and limited availability from natural resources, metabolites of the soft coral Pseudopterogorgia elisabethae, such as erogorgiaene and the pseudopterosines, represent important target molecules for chemical synthesis. We have now developed a particularly short and efficient route towards these marine diterpenes exploiting an operationally convenient enantioselective cobalt-catalyzed hydrovinylation as the chirogenic step. Other noteworthy C?C bond forming transformations include diastereoselective Lewis acid-mediated cyclizations, a Suzuki coupling and a carbonyl ene reaction. Starting from 4-methyl-styrene the anti-tubercular agent (+)-erogorgiaene (>98 % ee) was prepared in only 7 steps with 46 % overall yield. In addition, the synthesis of the pseudopterosin A aglycone was achieved in 12 steps with 30 % overall yield and, surprisingly, was found to exhibit a similar anti-inflammatory activity (inhibition of LPS-induced NF-κB activation) as a natural mixture of pseudopterosins A?D or iso-pseudopterosin A, prepared by β-D-xylosylation of the synthetic aglycone.
- Movahhed, Sohajl,Westphal, Julia,Kempa, Alexander,Schumacher, Christian Eric,Sperlich, Julia,Neud?rfl, J?rg-Martin,Teusch, Nicole,Hochgürtel, Matthias,Schmalz, Hans-Günther
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- Improvements and Applications of the Transition Metal-Free Asymmetric Allylic Alkylation using Grignard Reagents and Magnesium Alanates
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Two new N-heterocyclic carbene (NHC) ligands have been synthesized and employed in the transition metal-free asymmetric allylic alkylation (AAA) mediated by Grignard reagents and magnesium alanates. The employment of these ligands showed high yields and improved regio- and enantioselectivity in the formation of tertiary and quaternary stereocenters. Moreover, the low catalyst loading (up to 0.3 mol%) and high scalability (up to 10 mmol) of this improved methodology provide a convenient access to biologically active compounds and synthetically valuable intermediates.
- Grassi, David,Alexakis, Alexandre
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supporting information
p. 3171 - 3186
(2015/11/03)
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- Copper-free asymmetric allylic alkylation with a grignard reagent: Design of the ligand and mechanistic studies
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The Cu-free asymmetric allylic alkylation, catalysed by NHC, with Grignard reagents is reported on allyl bromide derivatives with good results. The enantioselectivity was quite homogeneous (around 85 % ee) on large and various substrates, regardless of the nature of the Grignard reagent. The formation of stereogenic quaternary centres was highly regioselective for both aliphatic and aromatic derivatives with good enantiomeric excess (up to 92 % ee). The methodology developed was found to be complementary with the Cu-catalysed version. Several new NHCs were tested with improved efficiency. In addition, mechanistic studies, using NMR spectroscopy, led to the discovery of the catalytically active species. Copyright
- Grassi, David,Dolka, Chrysanthi,Jackowski, Olivier,Alexakis, Alexandre
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supporting information
p. 1466 - 1475
(2013/02/25)
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- Application of supramolecular bidentate hybrid ligands in asymmetric hydroformylation
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In this study we report a novel class of supramolecular bidentate hybrid ligands in which the two inequivalent phosphorus units and pyridine moieties are covalently attached to a chiral scaffold and the supramolecular interactions are used as a second handle to control the coordination sphere around the transition-metal centre. The coordination chemistry of these ligands was investigated under hydroformylation conditions by high-pressure NMR and IR spectroscopy, revealing the formation of a single active species in which the phosphane ligand is in the axial position and the phosphoramidite adopts the equatorial position. These ligands were applied in the asymmetric Rh-catalysed hydroformylation of styrene and para-substituted analogues. In these hydroformylation reactions, modification of the electronic and steric properties of the zinc(II)-templates appear to have a significant influence on the activity and selectivity of the catalysis. In particular, zinc(II)-templates bearing more electron-withdrawing substituents led to an increase in enantioselectivity.
- Bellini, Rosalba,Reek, Joost N. H.
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p. 13510 - 13519,10
(2020/09/14)
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- Rhodium-catalyzed asymmetric coupling reaction of allylic ethers with arylboronic acids
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An asymmetric allylic substitution of simple allylic ethers with arylboronic acids in the presence of a rhodium(I)/(R)-DTBM-SEGPHOS catalyst has been developed. The reactions proceeded smoothly at room temperature to give the corresponding branch products with excellent regioselectivities and good to excellent enantioselectivities.
- Kiuchi, Hiroyoshi,Takahashi, Dai,Funaki, Kenji,Sato, Tetsuo,Oi, Shuichi
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supporting information
p. 4502 - 4505
(2012/10/29)
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- Enantioselective hydrovinylation via asymmetric counteranion-directed ruthenium catalysis
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The first Ru-catalyzed enantioselective hydrovinylation has been realized by using an asymmetric counteranion-directed catalysis strategy. Styrene derivatives react with ethylene in excellent yields and promising enantioselectivity using this approach. Th
- Jiang, Gaoxi,List, Benjamin
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supporting information; experimental part
p. 10022 - 10024
(2011/10/12)
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- Syntheses and applications of 2-phosphino-2′-alkoxy-1,1′- binaphthyl ligands. Development of a working model for asymmetric induction in hydrovinylation reactions
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Among the handful of monophosphine ligands that effect asymmetric hydrovinylation of vinylarenes, 2-diphenylphosphino-2′-methoxy-1,1′- binaphthyl (MOP) is among the most accessible. Addition of a methyl group at the 3′-position of this ligand significantl
- Saha, Biswajit,RajanBabu
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p. 2357 - 2363
(2007/10/03)
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- Palladium-catalyzed asymmetric hydrovinylation under mild conditions using monodentate chiral spiro phosphoramidite and phosphite ligands
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Palladium complexes of chiral spiro phosphoramidite and phosphite ligands are effective catalysts in the asymmetric hydrovinylation of vinylarenes with ethylene. The hydrovinylation products were obtained in modest selectivity with enantioselectivities up to 92% ee. The structures of the palladium catalysts have been analyzed by X-ray diffraction. The active catalyst contained one monodentate ligand. A kinetic resolution accompanied the isomerization of the hydrovinylation product in the reaction.
- Shi, Wen-Jian,Xie, Jian-Hua,Zhou, Qi-Lin
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p. 705 - 710
(2007/10/03)
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- Copper catalyzed enantioselective allylic substitution by MeMgX
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Methyl Grignard undergoes highly regio (>90/10) and enantioselective (ee 91-96%) copper catalyzed allylic substitution on cinnamyl-type chlorides. CuBr (3%) and 3.3% of a chiral phosphoramidite ligand are sufficient for a complete reaction. The synthesis of a precursor of (+)-Naproxen is described. The reaction can be extended to alkyl substituted allylic chlorides (ee 72%).
- Tissot-Croset, Karine,Alexakis, Alexandre
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p. 7375 - 7378
(2007/10/03)
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- Chiral benzyl centers through asymmetric catalysis. A three-step synthesis of (R)-(-)-α-curcumene via asymmetric hydrovinylation
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(Chemical Equation Presented) A three-step, two-pot procedure involving asymmetric hydrovinylation followed by Suzuki-Miyaura reaction represents by far the shortest synthesis of this popular bisabolane. Other applications for the synthesis of similar com
- Zhang, Aibin,RajanBabu
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p. 3159 - 3161
(2007/10/03)
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- Fine-tuning monophosphine ligands for enhanced enantioselectivity. Influence of chiral hemilabile pendant groups
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C2-Symmetric P-(2-X-aryl)-2,5-dialkylphospholanes (X = dioxolan-2-yl or dioxan-2-yl), designed on the basis of a working model for asymmetric induction, are effective ligands for the Ni(II)-catalyzed asymmetric hydrovinylation of styrenes. Excellent yields (>99%), selectivities for the desired 3-arylbutenes (>99%), high S/C ratios (>1200), and ee's (up to 91%) have been realized for a number of prototypical vinylarenes. In the dioxolane series, the selectivity depends on the configuration of the C 4 and C5 carbons.
- Zhang, Aibin,RajanBabu
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p. 1515 - 1517
(2007/10/03)
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- Chiral (β-Aminoalkyl)phosphines. Highly Efficient Phosphine Ligands for Catalytic Asymmetric Grignard Cross-Coupling
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New chiral (β-aminoalkyl)phosphines, RCH(NMe2)CH2PPh2 , were prepared by starting with optically active amino acids.The phosphines were used as ligands for nickel-catalyzed asymmetric cross-coupling of 1-arylethyl Grignard reagents (ArMeCHMgCl) with vinyl bromide.Coupling products of over 70percent enantiomeric excess (ee) were obtained in the reaction with the ligand Phephos, Valphos, Ilephos, PhGlyphos, ChGlyphos, or t-Leuphos.A mechanism involving complexation of the magnesium atom in the Grignard reagent with the amino group on the (β-aminoalkyl)phosphine ligand is proposed to account for the high stereoselectivity.The asymmetric cross-coupling was applied to the synthesis of optically active 2-arylpropionic acids.
- Hayashi, Tamio,Konishi, Mitsuo,Fukushima, Motoo,Kanehira, Koichi,Hioki, Takeshi,Kumada, Makoto
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p. 2195 - 2202
(2007/10/02)
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- Asymmetric Cross-coupling of Organozinc Reagents with Alkenyl Bromides Catalyzed by a Chiral Ferrocenylphosphine-Palladium Complex
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Organozinc reagents, prepared from secondary alkyl Grignard reagents (ArRCHMgCl: Ar=Ph, p-Tol; R=Me, Et) and excess zinc halides, were allowed to react with vinyl bromide and (E)-β-bromostyrene in the presence of dichloro(R)-N,N-dimethyl-1-(S)-2-(diphen
- Hayashi, Tamio,Hagihara, Toshiya,Katsuro, Yoshio,Kumada, Makoto
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p. 363 - 364
(2007/10/02)
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