54549-74-5Relevant academic research and scientific papers
Large-scale synthesis of a substituted d -phenylalanine using asymmetric hydrogenation
Fox, Martin E.,Jackson, Mark,Meek, Graham,Willets, Matthew
experimental part, p. 1163 - 1171 (2012/01/05)
A synthetic route to an N-BOC d-phenylalanine pharmaceutical intermediate suitable for rapid scale-up to 150-kg scale was required. A seven-step route based on asymmetric hydrogenation of an N-acetyl dehydroamino-acid was developed. Starting with terephthalic dialdehyde, monoreduction of one aldehyde group, Erlenmeyer condensation, and ring-opening/O-deacetylation with methanol provided the 4-(hydroxymethyl)-substituted dehydrophenylalanine hydrogenation substrate. Asymmetric hydrogenation of this enamide using [((R,R)-Ethyl-DuPhos) Rh(COD)BF4 proceeded in high enantiomeric excess. Subsequently, the cis-2,6-piperidyl group was introduced by mesylation/displacement, the BOC group was introduced, and acetyl and methyl ester groups were removed by basic hydrolysis. This route was used to manufacture 150 kg of the BOC amino acid 1.
In situ evaluation of kinetic resolution catalysts for nitroaldol by rationally designed fluorescence probe
Matsumoto, Takuya,Urano, Yasuteru,Takahashi, Yoshinori,Mori, Yusuke,Terai, Takuya,Nagano, Tetsuo
experimental part, p. 3616 - 3625 (2011/06/22)
Development of effective chemical catalysts is a key concern in organic chemistry. Therefore, convenient screening systems for chemical catalysts are required, and although some fluorescence-based HTS systems have been developed, little attempt has been made to apply them to asymmetric catalysts. Therefore, we tried to develop a chiral fluorescence probe which can evaluate the reactivity and enantioselectivity of asymmetric catalysts. We focused on kinetic resolution catalysts as a target of our novel fluorescence probe, employing β-elimination following acylation of nitroaldol. Once the hydroxyl group of nitroaldol is acylated, β-elimination occurs immediately, affording nitro olefin. Therefore, we designed and synthesized a fluorescence probe with an asymmetric nitroaldol moiety. Its fluorescence intensity decreases dramatically upon β-elimination, so the fluorescence decrease is an indicator of the reaction yield. Thus, the enantioselectivity of kinetic resolution catalysts can be assessed simply by measuring the fluorescence intensities of the reaction mixtures of the two enantiomers; it is not necessary to purify the product. This fluorescence probe revealed that benzotetramisole is a superior catalyst for kinetic resolution of nitroaldol. Furthermore, we established an HTS system for asymmetric catalysts, using a fluorescence probe and benzotetramisole. To our knowledge, this is the first fluorescence-based HTS system for asymmetric catalysts.
Oxidation of benzylic alcohols and ethers to carbonyl derivatives by nitric acid in dichloromethane
Strazzolini, Paolo,Runcio, Antonio
, p. 526 - 536 (2007/10/03)
Nitric acid in dichloromethane may be successfully employed for the oxidation of benzylic alcohols and ethers to the corresponding carbonyl compounds. The proposed method proved to be of general applicability, affording very good yields of aldehydes and ketones and showing interesting chemoselectivity in many instances, allowing competitive aromatic nitration to be avoided, as well as - in the case of aldehydes - any further oxidation to carboxylic acids. The reaction probably proceeds by a radical mechanism, the active species in the oxidation process being NO2. Competitive formation of nitro esters was observed in some cases, whereas poor results were obtained with allylic and non-benzylic substrates. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
Synthesis and antirheumatic activity of the metabolites of esonarimod
Noguchi, Toshiya,Onodera, Akira,Tomisawa, Kazuyuki,Yamashita, Miyuki,Takeshita, Kimiyo,Yokomori, Sadakazu
, p. 2713 - 2721 (2007/10/03)
We have developed esonarimod, (±)-2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid, as a new antirheumatic drug. Now we describe herein the preparation of the enantiomers of (±)-deacetylesonarimod, the pharmaceutically active metabolites of esonar
Highly efficient aerobic oxidation of benzylic and allylic alcohols by a simple catalyst system of [RuCl2(p-cymene)]2/Cs2CO3
Lee,Chang
, p. 7507 - 7510 (2007/10/03)
A new catalyst system of [RuCl2(p-cymene)]2/Cs2CO3 has been disclosed for highly efficient aerobic oxidation of activated alcohols to the corresponding carbonyl compounds, which is characterized by its high selectivity and activity, operational simplicity, and low air and moisture sensitivity. (C) 2000 Elsevier Science Ltd.
Stereocontrolled synthesis of polyketide libraries: Boron-mediated aldol reactions with aldehydes on solid support
Gennari, Cesare,Ceccarelli, Simona,Piarulli, Umberto,Aboutayab, Karim,Donghi, Monica,Paterson, Ian
, p. 14999 - 15016 (2007/10/03)
Two complementary classes of chiral boron enolates for adaptation to aldol additions to resin-bound aldehydes were studied: (i) the thioester- derived enolate 1 bearing chiral ligands on boron, and (ii) the chiral ketone-derived enolate 2. The viability of performing highly enantioselective, boron-mediated, aldol reactions was demonstrated by the preparation of resin-bound adducts 15 (91% ee) and 21 (88% ee). The solid phase aldol reactions of enolate 2 can be combined with an in situ reduction of the intermediate aldolate using LiBH4, leading to the controlled introduction of four contiguous stereocentres, as in 33 → 40 (>96% diastereoselectivity). The choice of linker is crucial and the available experimental evidence suggests that trityl and silyl linkers are optimal. This methodology should be amenable to the stereocontrolled synthesis of polyketide libraries.
1,4-dihydropyridines
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, (2008/06/13)
1,4-Dihydropyridines of the formula STR1 in which R1 is hydrogen, or alkyl optionally substituted by halogen, nitro, cyano, alkoxy, carboxyl, alkoxycarbonyl or carboxamide, R2 is hydrogen or alkyl, R3 is hydrogen, alkyl, carboxyl, alkoxycarbonyl or aryl optionally substituted by hydroxyalkyl, carboxyl, sulphoxy, acloxyalkyl, or STR2 R4 is alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, STR3 X is oxygen, sulphur or NH, and n is 1 to 6, or physiologically acceptable salts thereof, which are active in combating thromboembolic and ischaemic disorders.
The Liquid-phase Oxidation of the Methylbenzenes by the Cobalt-Copper-Bromide System
Okada, Toshihiko,Kamiya, Yoshio
, p. 2724 - 2727 (2007/10/02)
The liquid-phase oxidation of the methylbenzenes catalyzed by a catalyst system composed of cobalt(II) and copper(II) acetates and sodium bromide was carried out in the acetic acid at 150 deg C.The corresponding benzyl acetates and benzaldehydes were obtained in high selectivities in most cases.A nuclear-brominated product, i.e., 3-bromo-4-methoxytoluene was also obtained in the oxidation of p-methoxytoluene, wich has two different reaction sites, i.e., o-positions to the electron-donating methoxyl substituent and the benzyl position.However, the substitution of the bromide ion for the acetate ion in the catalyst system gave satisfactory selectivities for the side-chain oxidation products.In the p-xylene oxidation, α,α'-diacetoxy-p-xylene and p-(acetoxymethyl)benzoic acid were also obtained, as well as p-methylbenzyl acetate, though their amounts were small.The oxidation of polymethylbenzenes was also carried out.
