- Minisci-Type Alkylation of N-Heteroarenes by N-(Acyloxy)phthalimide Esters Mediated by a Hantzsch Ester and Blue LED Light
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A synthetic method that enables the Hantzsch ester-mediated Minisci-type C2-alkylation of quinolines, isoquinolines and pyridines by N-(acyloxy)phthalimide esters (NHPI) under blue LED (light emitting diode) light (456 nm) is described. Achieved under mild reaction conditions at room temperature, the metal-free synthetic protocol was shown to be applicable to primary, secondary and tertiary NHPIs to give the alkylated N-heterocyclic products in yields of 21–99%. On introducing a chiral phosphoric acid, an asymmetric version of the reaction was also realised and provided product enantiomeric excess (ee) values of 53–99%. The reaction mechanism was delineated to involve excitation of an electron-donor acceptor (EDA) complex, formed from weak electrostatic interactions between the Hantzsch ester and NHPI, which generates the posited radical species of the redox active ester that undergoes addition to the N-heterocycle.
- Kyne, Sara Helen,Li, Jiacheng,Siang Tan, Suan,Wai Hong Chan, Philip
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supporting information
(2022/01/11)
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- Systematic methodology for the development of biocatalytic hydrogen-borrowing cascades: Application to the synthesis of chiral α-substituted carboxylic acids from α-substituted α,β-unsaturated aldehydes
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Ene-reductases (ERs) are flavin dependent enzymes that catalyze the asymmetric reduction of activated carbon-carbon double bonds. In particular, α,β-unsaturated carbonyl compounds (e.g. enals and enones) as well as nitroalkenes are rapidly reduced. Conversely, α,β-unsaturated esters are poorly accepted substrates whereas free carboxylic acids are not converted at all. The only exceptions are α,β-unsaturated diacids, diesters as well as esters bearing an electron-withdrawing group in α- or β-position. Here, we present an alternative approach that has a general applicability for directly obtaining diverse chiral α-substituted carboxylic acids. This approach combines two enzyme classes, namely ERs and aldehyde dehydrogenases (Ald-DHs), in a concurrent reductive-oxidative biocatalytic cascade. This strategy has several advantages as the starting material is an α-substituted α,β-unsaturated aldehyde, a class of compounds extremely reactive for the reduction of the alkene moiety. Furthermore no external hydride source from a sacrificial substrate (e.g. glucose, formate) is required since the hydride for the first reductive step is liberated in the second oxidative step. Such a process is defined as a hydrogen-borrowing cascade. This methodology has wide applicability as it was successfully applied to the synthesis of chiral substituted hydrocinnamic acids, aliphatic acids, heterocycles and even acetylated amino acids with elevated yield, chemo- and stereo-selectivity. A systematic methodology for optimizing the hydrogen-borrowing two-enzyme synthesis of α-chiral substituted carboxylic acids was developed. This systematic methodology has general applicability for the development of diverse hydrogen-borrowing processes that possess the highest atom efficiency and the lowest environmental impact. This journal is
- Knaus, Tanja,Mutti, Francesco G.,Humphreys, Luke D.,Turner, Nicholas J.,Scrutton, Nigel S.
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supporting information
p. 223 - 233
(2015/02/19)
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- Asymmetric synthesis of unnatural amino acids and tamsulosin chiral intermediate
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An efficient and enantioselective hydrogenation of N-acetylamino phenyl acrylic acids was successfully developed by using ruthenium catalyst. This methodology is important in the field of pharmaceuticals and provides a new process for the preparation of unnatural amino acids and tamsulosin chiral intermediate.
- Arava, Veera Reddy,Amasa, Srinivasulu Reddy,Goud Bhatthula, Bharat Kumar,Kompella, Laxmi Srinivas,Matta, Venkata Prasad,Subha
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p. 2892 - 2897
(2013/09/02)
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- Chemoenzymatic synthesis of a mixed phosphine-phosphine oxide catalyst and its application to asymmetric allylation of aldehydes and hydrogenation of alkenes
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The chemoenzymatic synthesis of a Lewis basic phosphine-phosphine oxide organocatalyst from a cis-dihydrodiol metabolite of bromobenzene proceeds via a palladium-catalysed carbon-phosphorus bond coupling and a novel room temperature Arbuzov [2,3]-sigmatropic rearrangement of an allylic diphenylphosphinite. Allylation of aromatic aldehydes were catalysed by the Lewis basic organocatalyst giving homoallylic alcohols in up to 57% ee. This compound also functioned as a ligand for rhodium-catalysed asymmetric hydrogenation of acetamidoacrylate giving reduction products with ee values of up to 84%.
- Boyd, Derek R.,Bell, Mark,Dunne, Katherine S.,Kelly, Brian,Stevenson, Paul J.,Malone, John F.,Allen, Christopher C. R.
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experimental part
p. 1388 - 1395
(2012/03/27)
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- Convenient method for reduction of C-N double bonds in oximes, imines, and hydrazones using sodium Borohydride-Raney ni system
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(Chemical Equation Presented) A practical method has been developed for reduction of C-N double bond in oximes, imines, and hydrazones with sodium borohydride catalyzed by Raney Ni. The reactions were carried out in basic aqueous solution, and the desired products were obtained in moderate yields after a simple procedure. This method can be applied to synthesize simpler aliphatic or aromatic amines and its analogs. Copyright Taylor & Francis Group, LLC.
- Yang, Yihua,Liu, Shouxin,Li, Junzhang,Tian, Xia,Zhen, Xiaoli,Han, Jianrong
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experimental part
p. 2540 - 2554
(2012/07/27)
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- Efficient kinetic resolution of amino acids catalyzed by lipase AS 'Amano' via cleavage of an amide bond
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Herein the efficient kinetic resolution of non-natural alpha-amino acids catalyzed by lipase AS 'Amano' via cleaving the amide bond is reported. The starting materials were the corresponding amino acid amides and the amino acids were generated with ees of up to 99% with E values of >600. These results indicated that the lipase AS 'Amano' could be a powerful amide hydrolase for the kinetic resolution of amino acid starting from the corresponding amino acid amides.
- Wang, Bo,Liu, Yanfeng,Zhang, Dela,Feng, Yuhong,Li, Jiacheng
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p. 1338 - 1342,5
(2020/09/16)
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- Synthesis and application of peripherally alkyl-functionalized dendritic pyrphos ligands: Homogeneous-supported catalysts for enantioselective hydrogenation
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A new series of dendritic ligands with a chiral diphosphine located at the focal point have been synthesized through coupling of (R,R)-3,4-bis(biphenylphosphino)pyrrolidine (pyrphos) with peripherally alkyl-functionalized benzoic acid dendrons. These ligands were employed in the Rh-catalyzed asymmetric hydrogenation of prochiral dehydroamino acids, exhibiting excellent catalytic activities and enantioselectivities. The second-generation dendritic catalyst could be recovered by simple liquid-liquid biphasic separation and reused four times without serious loss of its activity and selectivity.
- Yi, Bing,He, Hua-Ping,Fan, Qing-Hua
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experimental part
p. 82 - 85
(2010/04/25)
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- Resolution of N-protected amino acid esters using whole cells of Candida parapsilosis ATCC 7330
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Whole cells of Candida parapsilosis ATCC 7330 were used for the resolution of N-acetyl amino acid esters. Excellent enantioselectivities (E = 40 to >500) were achieved for the resolution of N-protected protein and non-protein amino acid esters giving good yields (28-50%) and high enantiomeric excesses (up to >99%) for both enantiomers.
- Stella, Selvaraj,Chadha, Anju
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experimental part
p. 457 - 460
(2010/06/21)
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- Novel atropisomeric bisphosphine ligands with a bridge across the 5,5′-position of the biphenyl for asymmetric catalysis
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A new type of atropisomeric bisphosphine ligand 2 with a bridge across the 5,5′-position of the biphenyl has been developed. The axial chirality of this type of ligands can be retained by macrocyclic ring strain produced from 5,5′-linkage of the biphenyl
- Wei, Hao,Zhang, Yong Jian,Wang, Feijun,Zhang, Wanbin
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p. 482 - 488
(2008/09/19)
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- CHIRAL PHOSPHORUS COMPOUNDS
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The present invention provides P-chiral compounds of general formula (II) and (III): wherein at least one of R21, R25, R26 and R30 is independently selected from C1-4 alkyl, CF3, C1-4 alkoxy, phenyl and benzyloxy and the remaining substituents selected from R21, R25, R26 and R30 are hydrogen; at least one of R22, R24, R27 and R29 are independently selected from C1-4 alkyl, CF3, C1-4 alkoxy, phenyl and benzyloxy and the remaining substituents selected from R22, R24, R27 and R29 are hydrogen; and R23 and R28 are independently selected from hydrogen, C1-4 alkyl, CF3, C1-4 alkoxy, phenyl and benzyloxy; Formula (III): wherein at least one of R21, R25, R26 and R30 is independently selected from phenyl and benzyloxy and the remaining substituents selected from R21, R25, R26 and R30 are hydrogen; and R22, R23, R24, R27, R28 and R29 are independently selected from hydrogen, C1-4 alkyl, CF3, C1-4 alkoxy, phenyl and benzyloxy.wherein at least one of R21, R25, R26 and R30 is independently selected from phenyl and benzyloxy and the remaining substituents selected from R21, R25, R26 and R30 are hydrogen; and R22, R23, R24, R27, R28 and R29 are independently selected from hydrogen, C1-4 alkyl, CF3, C1-4 alkoxy, phenyl and benzyloxy.
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Page/Page column 37-39
(2008/12/04)
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- Synthesis of a novel spiro bisphosphinite ligand and its application in Rh-catalyzed asymmetric hydrogenation
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A novel, chiral bisphosphinite ligand (R)-SpiroBIP has been synthesized. The rhodium complex of the ligand was found to be highly enantioselective in the asymmetric hydrogenation of α-dehydroamino acid derivatives.
- Guo, Zhenqiu,Guan, Xiaoyu,Chen, Zhiyong
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p. 468 - 473
(2007/10/03)
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- Melanocortin receptor ligands
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Disclosed are MC-4 and/or MC-3 receptor ligands, the ligands having a structure according to Formula (I): wherein R2, R4, R4′, R5, R6, R6′, R7, R8, R8′, R9, R9′, R10, Ar, Z1, Z2, Z3, X, B, D, p, q, r and s are as described in the specification and claims, and optical isomers, diastereomers or enantiomers thereof; pharmaceutically-acceptable salts, hydrates, and biohydrolyzable esters, amides or imides thereof. Also disclosed are pharmaceutical compositions comprising the ligands of Formula (I), as well as methods of treating diseases mediate by the MC-4/MC-3 receptors, as described in the Detailed Descriptions section of the specification.
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Page/Page column 56
(2010/11/08)
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- Rh-catalyzed asymmetric hydrogenation of prochiral olefins with a dynamic library of chiral TROPOS phosphorus ligands
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A library of 19 chiral tropos phosphorus ligands, based on a flexible (tropos) biphenol unit and a chiral P-bound alcohol (11 phosphites) or secondary amine (8 phosphoramidites), was synthesized. These ligands were screened, individually and as a combination of two, in the rhodium-catalyzed asymmetric hydrogenation of dehydro-α-amino acids, dehydro-β-amino acids, enamides and dimethyl itaconate. ee values up to 98% were obtained for the dehydro-α-amino acids, by using the best combination of ligands, a phosphite [4-P(O)2O] and a phosphora midite [13-P(O)2N]. Kinetic studies of the reactions with the single ligands and with the combination of phosphite [4-P(O)2O] and phosphoramidite [13-P(O) 2N] have shown that the phosphite, despite being less enantioselective, promotes the hydrogenation of methyl 2-acetamidoacrylate and methyl 2-acetamidocinnamate faster than the mixture of the same phosphite with the phosphoramidite, while the phosphoramidite alone is much less active. In this way, the reaction was optimized by lowering the phosphite/phosphoramidite ratio (the best ratio is 0.25 equiv phosphite/1.75 equiv phosphoramidite) with a resulting improvement of the product enantiomeric excess. A simple mathematical model for a better understanding of the variation of the enantiomeric excess with the phosphite/ phosphoramidite ratio is also presented.
- Monti, Chiara,Gennari, Cesare,Piarulli, Umberto,De Vries, Johannes G.,De Vries, Andre H. M.,Lefort, Laurent
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p. 6701 - 6717
(2007/10/03)
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- H8-MonoPhos and its application in catalytic enantioselective hydrogenation of α-dehydroamino acids
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H8-MonoPhos, a new stable and readily soluble monodentate phosphoramidite ligand, has been facilely prepared from H8-BINOL. The ligand achieved up to 99.9% ee and 96.7% ee in hydrogenation of dehydroalanine and dehydrohomophenylalani
- Zeng, Qingle,Liu, Hui,Mi, Aiqiao,Jiang, Yaozhong,Li, Xingshu,Choi, Michael C.K,Chan, Albert S.C
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p. 8799 - 8803
(2007/10/03)
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- Process for production of optically active n-protected-n-methyl-phenylalanine derivative
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There is provided a process for industrially and efficiently producing an optically active N-protected-N-methyl-4-halogenophenylalanine at a high purity, which is useful as an intermediate for the production of pharmaceutical agents. An optically active N-protected-N-methyl-4-halogenophenylalanine (including the free form and/or the salt form thereof) purified to a high purity is produced by way of the deposition and isolation in the form of salt (DCHA salt or the like) from an optically active N-protected-N-methyl-4-halogenophenylalanine containing at least the optical isomer thereof as an impurity. Because the intended compound at a high purity can be recovered and obtained at a high yield, the process of the present invention is very useful as a process for producing the intermediate for the production of pharmaceutical agents.
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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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- Efficient chemoenzymatic synthesis of enantiomerically pure α-amino acids
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A general two-step chemoenzymatic synthesis for enantiomerically pure natural and nonnatural α-amino acids is presented. In the first step of the sequence, the ubiquitous educts aldehyde, amide and carbon monoxide react by palladium-catalyzed amidocarbonylation to afford the racemic N-acyl amino acids in excellent yields. In the second step, enzymatic enantioselective hydrolysis yields the free optically pure a-amino acid and the other enantiomer as the N-acyl derivative, both in optical purities of 85-99.5% ee. The advantage of the chemoenzymatic process compared to other amino acid synthesis are demonstrated by the preparation of various functionalized (-OR, -Cl, -F, -SR) α-amino acids on a 10-g scale.
- Beller, Matthias,Eckert, Markus,Geissler, Holger,Napierski, Bernd,Rebenstock, Heinz-Peter,Holla, E. Wolfgang
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p. 935 - 941
(2007/10/03)
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- Acylase I catalysed hydrolysis of para-substituted (S)-phenylalanine derivatives from mixtures of the racemic ortho- and para-substituted isomers
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para-Substituted (S)-phenylalanines may be obtained by treatment of the corresponding mixtures of ortho- and para-substituted N-acetyl-(RS)- phenylalanines with Acylase I from porcine kidney. The selectivity of the enzyme may be attributed to its evolution to digest peptide derivatives of (S)-phenylalanine and (S)-tyrosine.
- Easton, Christopher J.,Harper, Jason B.
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p. 5269 - 5272
(2007/10/03)
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