- New and efficient conditions for the Z-selective synthesis of unsaturated esters by the Horner-Wadsworth-Emmons olefination
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The Horner-Wadsworth-Emmons reaction of both 1 (Still's reagent) and 2 (Ando's reagent) with aldehydes was studied. Tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1) was shown to be an efficient additive when the reaction was performed in THF at -78°C. Selectivities close to 95% were obtained in the condensation of 1 with aromatic aldehydes. The use of a 5-fold excess of 18C6 in this reaction had already been reported. However, we have defined conditions in which only catalytic amounts are required.
- Touchard, Fran?ois P.
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Read Online
- Discovery of novel 5,5-diarylpentadienamides as orally available transient receptor potential vanilloid 1 (TRPV1) antagonists
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We have developed a novel and potent chemical series of 5,5-diphenylpentadienamides for targeting TRPV1 in vitro and in vivo. In this investigation, we examined a variety of replacements for the 5-position of dienamides with the goal of addressing issues related to pharmacokinetics. Our data suggest that substitution with alkoxy groups on the phenyl ring at the 5-position increases their ability to penetrate the blood-brain barrier. This investigation culminated in the discovery of compound (R)-36b, which showed a good pharmacokinetic profile. In vivo, compound (R)-36b was found to be effective at reversing mechanical allodynia in rats in a dose-dependent manner, and it reversed thermal hyperalgesia in a model of neuropathic pain induced by sciatic nerve injury.
- Saku, Osamu,Ishida, Hiroshi,Atsumi, Eri,Sugimoto, Yoshiyuki,Kodaira, Hiroshi,Kato, Yoshimitsu,Shirakura, Shiro,Nakasato, Yoshisuke
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experimental part
p. 3436 - 3451
(2012/06/04)
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- Diastereoselective method of preparing olefins by means of the horner-wadsworthemmons reaction, comprising the addition of a tris-(polyoxaalkyl)-amine sequestering agent
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The invention relates to a process for the diastereoselective preparation of olefins via the Homer-Wadsworth-Emmons reaction, which consists in reacting at low temperature a phosphonate with a carbonyl derivative in the presence of a base in a suitable solvent, characterized in that a tris(polyoxaalkyl)amine sequestering reagent of formula (I): N—[CHR1—CHR2—O—(CHR3—CHR4—O)n—R5]3 (I), wherein: n is an integer between 0 and 10; R1, R2, R3 and R4 may be identical or different, and represent a hydrogen atom or an alkyl radical containing from 1 to 4 carbon atoms; R5 represents a hydrogen atom, an alkyl or cycloalkyl radical containing up to 12 carbon atoms, a phenyl radical or a radical of formula —CμH2μ-Φ, or CmH2m+1-Φ-, with m being an integer between 1 and 12 and Φ being a phenyl radical; is added in an amount that is sufficient to increase the diastereoselectivity of the olefin.
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Page/Page column 5-6
(2010/11/08)
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- Enantioselective Catalytic Epoxidation of Cinnamate Esters
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A broad study of the (salen)Mn(III)-catalyzed asymmetric epoxidation of cis-cinnamate esters reveals that the steric properties of the ester group have a profound influence on enantioselectivity in the epoxidation reaction, with bulkier esters affording highest ee's.The sensitivity of the reaction selectivity to the steric properties of the cis-alkene are consistent with a "skewed" side-on approach of olefin to the metal -oxo.The electronic properties of the substrate arene ring substituents do not correlate with epoxidation ee, but instead with the cis/trans partitioning of product formation.Evidence is provided for a non-polar inter mediate in a stepwise oxygen-atom-transfer mechanism.The presence of pyridine N-oxide derivatives has a significant effect on catalysts rates and total turnovers, but negligible influence on the stereoselectivity of epoxidation.A mechanistic basis for the role of these additives is proposed.The synthetic applicability of the cinnamate epoxidation methodology is illustrated in the highly enantioslective synthesis of diltiazem.
- Jacobsen, Eric N.,Deng, Li,Furukawa, Yoshiro,Martinez, Luis E.
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p. 4323 - 4334
(2007/10/02)
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- Lewis Acid Catalysis of Photochemical Reactions. 7. Photodimerization and Cross-Cycloaddition of Cinnamic Esters
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The effects of Lewis acid complexation upon the molecular structure, solid-state photodimerization, and solution dimerization and cross-cycloaddition of cinnamic esters have been investigated.Comparison of crystal structures for free and SnCl4-complexed ethyl cinnamate indicates that the enone double bonds are lengthened, the single bonds are shortened, and the enone conformation changes from s-cis to s-trans upon complexation.These changes are consistent with calculated changes in ? bonding and net charges.Solid-state photodimerization of free and complexed cinnamic esters and related molecules yield syn head-to-tail (α-truxillate) dimers.In most cases the Lewis acid complexes dimerize more efficiently and stereoselectively than the free esters.Photodimerization and cross-cycloaddition of methyl cinnamate in dilute solution is also catalyzed by Lewis acids.The mechanism of these reactions involves electronic excitation of a ground-state methyl cinnamate-Lewis acid complex followed by reaction of the excited complex with ground-state ester (dimerization) or simple olefin (cross-cycloaddition).The catalytic effect of Lewis acids is attributed to an increase in excited-state lifetime and reactivity.
- Lewis, Frederick D.,Quillen, Suzanne L.,Hale, Paul D.,Oxman, Joe D
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p. 1261 - 1267
(2007/10/02)
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- Lewis Acid Catalysis of Photochemical Reactions. 4. Selective Isomerization of Cinnamic Esters
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The spectroscopic properties and photoisomerization reactions of several (E)- and (Z)-cinnamic esters, bis cinnamic esters, and model esters and lactones in the presence and absence of Lewis acids have been investigated.The use of Lewis acids such as BF3
- Lewis, Frederick D.,Oxman, Joe D.,Gibson, Lester L.,Hampsch, Hilary L.,Quillen, Suzanne L.
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p. 3005 - 3015
(2007/10/02)
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