- Mechanistically Guided One Pot Synthesis of Phosphine-Phosphite and Its Implication in Asymmetric Hydrogenation
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Although hybrid bidentate ligands are known to yield highly enantioselective products in asymmetric hydrogenation (AH), synthesis of these ligands is an arduous process. Herein, a one pot, atom-economic synthesis of a hybrid phosphine-phosphite (L1) is reported. After understanding the reactivity difference between an O-nucleophile versus C-nucleophile, one pot synthesis of Senphos (L1) was achieved (72 %). When L1 was treated with [Rh], 31P NMR revealed bidentate coordination to Rh. Senphos, in the presence of rhodium, catalyzes the AH of Methyl-2-acetamido-3-phenylacrylate and discloses an unprecedented turn over frequency of 2289, along with excellent enantio-selectivity (92 %). The generality is demonstrated by hydrogenating an array of alkenes. The AH operates under mild conditions of 1–2 bar H2 pressure, at room temperature. The practical relevance of L1 is demonstrated by scaling-up the reaction to 1 g and by synthesizing DOPA, a drug widely employed for the treatment of Parkinson's disease. Computational insights indicate that the R isomer is preferred by 3.8 kcal/mol over the S isomer.
- Sen, Anirban,Kumar, Rohit,Pandey, Swechchha,Vipin Raj,Kumar, Pawan,Vanka, Kumar,Chikkali, Samir H.
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- Diaza-Crown Ether-Bridged Chiral Diphosphoramidite Ligands: Synthesis and Applications in Asymmetric Catalysis
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A small library of diaza-crown ether-bridged chiral diphosphoramidite ligands was prepared. In the rhodium-catalyzed asymmetric hydrogenation and hydroformylation reactions, these ligands exhibited distinct properties in catalytic activity and/or enantioselectivity. Hydrogenated products with opposite absolute configurations could be obtained in high yields with excellent ee values by utilizing (S,S)-L1 and (S,S)-L3, respectively. Meanwhile, the addition of alkali metal cations caused variations in catalytic outcomes, showing the supramolecular tunability of these Rh/diphosphoramidite catalytic systems.
- Luo, Yier,Ouyang, Guanghui,Tang, Yuping,He, Yan-Mei,Fan, Qing-Hua
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p. 8176 - 8184
(2020/07/15)
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- Melphalan intermediate and preparation method thereof
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The invention discloses a Melphalan intermediate and a preparation method thereof. The Melphalan intermediate is prepared by acidifying a compound p-nitrobenzaldehyde under the action of methanol, a hydrochloric acid solvent, etc. The preparation method has a route with mild reaction conditions, is higher than an existing preparation method in yield, is economical and effective, and is suitable for large-scale industrial production. The synthesis route is as shown in the description.
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- Temperature-controlled bidirectional enantioselectivity in a dynamic catalyst for asymmetric hydrogenation
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Asymmetric catalysis using enantiomerically pure catalysts is one of the most widely used methods for the preparation of enantiomerically pure compounds. The separate synthesis of both enantiomerically pure compounds requires tedious and time-consuming pr
- Storch, Golo,Trapp, Oliver
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p. 3580 - 3586
(2015/03/18)
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- Asymmetric chemoenzymatic synthesis of N-acetyl-α-amino esters based on lipase-catalyzed kinetic resolutions through interesterification reactions
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Several phenylalanine analogs have been synthesized through a four-step route starting from easily available ethyl acetamidocyanoacetate. In a first reaction, and making use of phase transfer catalysts, this compound reacted with several alkyl halides, being benzyltributylammonium chloride identified as the best one for the production of a series of quaternary amino acids in moderate to excellent yields (52-95%). Then, the corresponding N-acetyl-phenylalanine methyl and allyl ester derivatives were obtained through acidic hydrolysis, esterification, and N-acetylation. Rhizomucor miehei lipase was found as a versatile enzyme for the resolution of these amino esters, finding the best results through interesterification reactions with butyl butyrate in acetonitrile. A great influence in the stereoselectivity was found depending on the chemical structure of the compound, achieving for the non- or para-substituted in the phenyl ring excellent stereoselectivities, being moderate for the meta-nitro derivative, while the ortho-nitro amino ester did not react.
- Da Silva, Marcos Reinaldo,De Mattos, Marcos Carlos,De Oliveira, Maria Da Concei??o Ferreira,De Lemos, Telma Leda Gomes,Ricardo, Nágila Maria Pontes Silva,De Gonzalo, Gonzalo,Lavandera, Iván,Gotor-Fernández, Vicente,Gotor, Vicente
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p. 2264 - 2271
(2014/03/21)
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- Synthesis and study of 2-acetyl amino-3-[4-(2-amino-5-sulfo-phenylazo)- phenyl]-propionic acid: A new class of inhibitor for hen egg white lysozyme amyloidogenesis
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The compounds capable of blocking the aggregation of amyloidogenic proteins may have therapeutic potentials. We report on the synthesis of 2-acetyl amino-3-[4-(2-amino-5-sulfo-phenylazo)-phenyl]-propionic acid as an HEWL (hen egg white lysozyme) amyloid inhibitor starting from phenylalanine. The compounds arrest the monomers and exhibit anti-aggregating activity. Moreover, the acetyl derivative 1 served as a better inhibitor than the trifluoroacetyl derivative 2 against in vitro amyloid fibrillogenesis of the HEWL model system.
- Maity, Sibaprasad,Kumar, Ravi,Maity, Suman Kumar,Jana, Poulami,Bera, Santu,Haldar, Debasish
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p. 530 - 536
(2013/05/22)
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- Damage of aromatic amino acids by the atmospheric free radical oxidant NO3 in the presence of NO2, N2O4, O3 and O2
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Analysis of the products formed in the reaction of NO3 with the N- and C-protected aromatic amino acids 1-5, which was performed under conditions that simulate exposure of biosurfaces to environmental pollutants, revealed insight how this impor
- Goeschen, Catrin,Wibowo, Natalia,White, Jonathan M.,Wille, Uta
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experimental part
p. 3380 - 3385
(2011/06/20)
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- Enantioselective hydrogenation of α-dehydroamino acid esters catalyzed by rhodium complexes with chiral bisaminophosphine ligands
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A highly efficient strategy for the synthesis of a series of chiral bisaminophosphine ligands was well established with several remarkable features. The synthetic utility of these ligands was explored for rhodium-catalyzed asymmetric hydrogenations of α-d
- Sun, Xianfeng,Li, Wei,Zhou, Le,Zhang, Xumu
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supporting information; experimental part
p. 1150 - 1154
(2010/06/20)
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- Supramolecular chiral phosphorous ligands based on a [2]pseudorotaxane complex for asymmetric hydrogenation
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A new type of supramolecular chiral phosphorus-based ligands was prepared from easily available monodentate ligands through complexation between dibenzylammonium salt and dibenzo[24]crown-8 macrocycle. Rhodium complexes with these supramolecular ligands w
- Li, Yong,Feng, Yu,He, Yan-Mei,Chen, Fei,Pan, Jie,Fan, Qing-Hua
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p. 2878 - 2881
(2008/09/21)
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- Rational design of MOFs constructed from modified aromatic amino acids
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Three Phe and Tyr derivatives, 2-amino-3-(4-aminophenyl)-propionic acid (AAP), 3E-[5-(2-amino-2-carboxyethyl)-2-methoxyphenyl]-acrylic acid (AMPA) and 3-(4-aminophenyl)-2-(carboxymethyl-amino)-propionic acid (ACP) have been chosen as the ligands to constr
- Xie, Yu,Yu, Zhaopeng,Huang, Xiaoying,Wang, Zhiyong,Niu, Liwen,Teng, Maikun,Li, Jing
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p. 9399 - 9405
(2008/09/21)
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- A comparison of phosphaferrocene and phospharuthenocene ligands in Rh +-catalysed enamide hydrogenation reactions: Superior performance of the phospharuthenocene
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Enantiopure Cp*-substituted 3.4-dimethyl-5-phenylphosphametallocene- 2-methanols (M=Fe, Ru) have been prepared from the corresponding 2-carboxy-(-)-menthylphospholide anion and elaborated into 2-CH 2PPh2 phosphametallocenes (13: M =
- Carmichael, Duncan,Goldet, Gabrielle,Klankermayer, Juergen,Ricard, Louis,Seeboth, Nicolas,Stankevic, Marek
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p. 5492 - 5502
(2008/03/12)
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- Design and preparation of a chiral ligand based on a pseudorotaxane skeleton: Application to rhodium-catalyzed enantioselective hydrogenation of enamides
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We have prepared a novel pseudorotaxane molecule which works as a chiral bidentate ligand having a phosphine moiety in an axle and a phosphite moiety in a wheel as two coordination sites and applied it successfully to the rhodium-catalyzed enantioselectiv
- Hattori, Gaku,Hori, Tetsuharu,Miyake, Yoshihiro,Nishibayashi, Yoshiaki
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p. 12930 - 12931
(2008/04/11)
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- Dendritic MonoPhos: synthesis and application in Rh-catalyzed asymmetric hydrogenation
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A new class of dendritic monodentate phosphoramidite ligands were synthesized through substitution of the dimethylamino moiety in MonoPhos by the Frechet-type dendritic wedge and applied in the asymmetric hydrogenation of α-dehydroamino acid esters and di
- Tang, Wei-Jun,Huang, Yi-Yong,He, Yan-Mei,Fan, Qing-Hua
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p. 536 - 543
(2007/10/03)
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- Polyethylene glycol as an environmentally friendly and recyclable reaction medium for enantioselective hydrogenation
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Polyethylene glycol (PEG) was found to be an inexpensive, non-toxic and recyclable reaction medium for ruthenium- and rhodium-catalyzed asymmetric hydrogenation of 2-arylacrylic acids (Ru-catalyzed C=C bond reduction), enamides (Rh-catalyzed C=C bond reduction), β-keto esters and simple aromatic ketones (Ru-catalyzed C=O bond reduction). In all cases, high catalytic activities and enantioselectivities have been achieved, which are comparable to those obtained in conventional organic solvent systems. The Ru and Rh catalysts prepared with commercially available chiral diphosphine ligands could be readily recycled by simple extraction, as in the case of ionic liquids, and reused up to nine times without obvious loss of catalytic activity and enantioselectivity. The reduced products were obtained from the extracts in high isolated yields. These results indicate that PEGs as new reaction media are attractive alternatives to room temperature ionic liquids.
- Zhou, Hai-Feng,Fan, Qing-Hua,Tang, Wei-Jun,Xu, Li-Jin,He, Yan-Mei,Deng, Guo-Jun,Zhao, Li-Wen,Gu, Lian-Quan,Chan, Albert S. C.
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p. 2172 - 2182
(2007/10/03)
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- Synthesis of a novel spiro bisphosphinamidite ligand for highly enantioselective hydrogenation
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A novel chiral bisphosphinamidite ligand SpiroNP has been synthesized. The rhodium complex of this ligand has been found to be highly active and enantioselective in the asymmetric hydrogenation of (Z)-2-acetamidoacrylic acid derivatives and α,β-unsaturated carboxylic acid derivatives.
- Lin, Ching Wen,Lin, Chi-Ching,Lam, Louis F.-L.,Au-Yeung, Terry T.-L.,Chan, Albert S.C.
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p. 7379 - 7381
(2007/10/03)
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- Ligand-free palladium catalysed Heck reaction of methyl 2-acetamido acrylate and aryl bromides as key step in the synthesis of enantiopure substituted phenylalanines
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A range of substituted aryl bromides were coupled with methyl 2-acetamido acrylate using ligand-free palladium catalysis. Subsequently asymmetric hydrogenation with Rh/MonoPhos yielded substituted phenylalanines in high enantioselectivities (e.e. 92-99%).
- Willans, Charlotte E.,Mulders, Jan M.C.A.,de Vries, Johannes G.,de Vries, André H.M.
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p. 494 - 497
(2007/10/03)
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- Monodentate Phosphoramidites: A Breakthrough in Rhodium-Catalysed Asymmetric Hydrogenation of Olefins
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Monodentate phosphoramidites based on BINOL or substituted BINOL are excellent ligands for the rhodium-catalysed asymmetric hydrogenation of olefins. Very high enantioselectivities were obtained with MonoPhos (7a) the simplest member of this class, a ligand that is prepared in a single step from BINOL and HMPT. Turnover numbers up to 6000 have been obtained in the hydrogenation of dehydroamino acid derivatives. Enantioselectivities in the hydrogenation of dehydroamino acids are solvent dependent; in non-protic solvents they range from 95-99%. Itaconic acid and its dimethyl ester could be hydrogenated with 96 and 94% e.e., respectively. Hydrogenation of aromatic enamides gave the corresponding acylated amines in 86-94% e.e. Several analogous phosphoramidite ligands have been pre-pared. Surprisingly, bidentate ligands gave poorer results, both in terms of rate as well as enantioselectivity. Taddol-based phosphoramidites led to poor e.e. and slow rates. Methyl substituents at the 3,3′-position of BINOL led to a sharply reduced rate and a somewhat lower enantioselectivity. Bromo substituents at the 6,6′-position led to a slightly reduced rate but little effect was seen on enantioselectivity. Use of octahydro-MonoPhos (11) gave results that were very similar to those obtained with 7a. The rate of the reaction is dependent on the hydrogen pressure, however, the enantioselectivity is not affected. The rate of the dehydroamino acid hydrogenation also increases if the ligand to rhodium ratio is reduced from 2.2 to 1.5 or even to 1.0; yet, there is no deleterious effect on the enantioselectivity. Catalytic activity ceases with L/Rh = 3 when dehydroamino acid derivatives were used as substrate. The reaction shows a positive non-linear effect, which confirms the presence of Rh-complexes with more than one ligand. Following the hydrogenation of methyl 2-acetamidocinnnamate with Rh(nbd)2BF4/7a by electrospray mass spectrometry showed the presence of several rhodium species. Notable are the presence of [Rh(7a)]3+ and [Rh(7a)]4+. There is at present insufficient evidence to conclude if the active catalytic species carries one or two ligands. In view of the low cost of MonoPhos this invention might well lead to a broader application of asymmetric olefin hydrogenation for the production of enantiopure amino acids and amines.
- Van Den Berg, Michel,Minnaard, Adriaan J.,Haak, Robert M.,Leeman, Michel,Schudde, Ebe P.,Meetsma, Auke,Feringa, Ben L.,De Vries, André H. M.,Maljaars, C. Elizabeth P.,Willans, Charlotte E.,Hyett, David,Boogers, Jeroen A. F.,Henderickx, Hubertus J. W.,De Vries, Johannes G.
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p. 308 - 323
(2007/10/03)
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- Modified BINAPO ligands for Rh-catalysed enantioselective hydrogenation of acetamidoacrylic acids and esters
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(S)- and (R)-2,2′-Bis[bis(3,5-dimethylphenyl)phosphinoyl]-5,5′,6, 6′,7,7′,8,8′-octahydro-1,1′-binaphthyl (Xyl-H8-BINAPO) were synthesised by reacting chlorobis(3,5-dimethylphenyl)phosphine with (S)- and (R)-2,2′-dihydroxyl-5,5′,6,6′,7,7′,8,8′-
- Guo, Rongwei,Au-Yeung, Terry T.-L.,Wu, Jing,Choi, Michael C. K.,Chan, Albert S. C.
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p. 2519 - 2522
(2007/10/03)
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- Synthesis of new chiral monodentate phosphines and their use in asymmetric hydrogenation
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A general synthesis of chiral 4,5-dihydro-3H-dinaphthophosphepines 1a-g is described. The resulting ligands represent a new class of monodentate chiral phosphines. First applications of 1a-g in the rhodium-catalyzed asymmetric hydrogenation of unsaturated
- Junge, Kathrin,Oehme, Günther,Monsees, Axel,Riermeier, Thomas,Dingerdissen, Uwe,Beller, Matthias
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p. 4977 - 4980
(2007/10/03)
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- A comparison of the asymmetric hydrogenation catalyzed by rhodium complexes containing chiral ligands with a binaphthyl unit and those with a 5,5′,6,6′,7,7′,8,8′-octahydro-binaphthyl unit
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The chiral ligands H8-BINAPO and H8-BDPAB were synthesized by reacting chlorodiphenylphosphine with H8-BINOL and H8-BINAM, respectively. Applications of these ligands in the Rh-catalyzed enantioselective hydrogenation of a variety of (Z)-acetamido-3-arylacrylic acid methyl esters provided chiral amino acid derivatives with good to excellent enantioselectivities (H8-BINAPO: up to 84.0% e.e.; H8-BDPAB: up to 97.1% e.e.). In the hydrogenation of acetamidoacrylic acid, 99% e.e. was obtained when a [Rh(H8-BDPAB)]+ catalyst was used. The catalytic activities and enantioselectivities of [Rh(H8-BINAPO)]+ and [Rh(H8-BDPAB]+ are substantially better than those obtained with the corresponding rhodium catalysts containing BINAPO (up to 64% e.e.) and BDPAB (up to 92.6% e.e.).
- Zhang, Fu-Yao,Kwok, Wai Him,Chan, Albert S.C.
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p. 2337 - 2342
(2007/10/03)
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- Asymmetric hydrogenation of dehydroamino acid derivatives catalyzed by a new aminophosphine phosphinite ligand derived from ketopinic acid
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A new chiral aminophosphine phosphinite N,O-bis(diphenylphosphino)-(1S,2R)-1-(N-methylamino) methyl-2-hydroxyl-7,7-dimethylbicyclo[2.2.1]heptane was synthesized from ketopinic acid and its application to the asymmetric hydrogenation of dehydroamino acid d
- Li, Xingshu,Lou, Rongliang,Yeung, Chi-Hung,Chan, Albert S. C.,Wong, Wai Kwok
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p. 2077 - 2082
(2007/10/03)
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- Method for preparing enantiomeric forms of amino alkylaminophenyl propanoic acid
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A process for preparing an enantiomeric form of 2-amino-3-(4-alkylaminophenyl)-propanoic acid of formula (I) or a salt thereof: STR1 in which Alk represents an alkyl radical containing 1 to 2 carbon atoms, from (L)-phenylalanine to obtain the (S)-enantiomer of 2-amino-3-(4-alkylaminophenyl)-propanoic acid, or from (D)-phenylalanine to obtain the (R)-enantiomer of 2-amino-3-(4-alkylaminophenyl)propanoic acid.
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- A highly effective phosphinite ligand derived from D-mannitol for Rh- catalyzed asymmetric hydrogenation
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A novel chiral phosphinite 1,2,5,6-di-isopropylidene-3, 4- bis(diphenylphosphino)-D-mannitol was prepared and its rhodium complex was found to be an effective catalyst for the asymmetric hydrogenation of amidoacrylic acid and its derivatives with product ee's ranging from 90% to 97%.
- Chen, Yixin,Li, Xingshu,Tong, Siu-Kuen,Choi, Michael C.K.,Chan, Albert S.C.
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p. 957 - 960
(2007/10/03)
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- DERIVATIVES OF BETA-ADRENERGIC ANTAGONISTS
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Molecular structures of β-adrenergic antagonists are modified to produce biologically active compounds. The β-antagonists are modified to form molecules of the general structure: STR1 wherein R is most generally R"--OCH 2--, and in some instances is R"--, and R"=an aryl or substituted aryl moiety; R'=--H,--CH 3, or a short chain alkyl moiety; and Y=--OH, or more usually,--OAX or--NHAX, where A=an alkyl, aryl, or aralkyl moiety, and X=a terminal grouping, such as--CH 3,--CF 3 or--(CH 2) n COOH; or AX may be a carrier moiety consisting of a defined peptide or protein. "
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