19131-99-8Relevant academic research and scientific papers
Solid-phase supported chiral lithium amides used in deprotonation reactions
Johansson, Anna,Abrahamsson, Peter,Davidsson, Oejvind
, p. 1261 - 1266 (2003)
The lithium salt of polymer supported phenylethyl amine showed surprisingly high enantioselectivity in the asymmetric deprotonation reaction of cyclohexene oxide. The polymer supported chiral lithium amide base also proved to be more reactive compared to the free chiral lithium amide base. This is a new insight in the development and mechanism of chiral lithium amide bases used in asymmetric reactions.
Screening and characterization of a diverse panel of metagenomic imine reductases for biocatalytic reductive amination
Marshall, James R.,Yao, Peiyuan,Montgomery, Sarah L.,Finnigan, James D.,Thorpe, Thomas W.,Palmer, Ryan B.,Mangas-Sanchez, Juan,Duncan, Richard A. M.,Heath, Rachel S.,Graham, Kirsty M.,Cook, Darren J.,Charnock, Simon J.,Turner, Nicholas J.
, p. 140 - 148 (2021/01/04)
Finding faster and simpler ways to screen protein sequence space to enable the identification of new biocatalysts for asymmetric synthesis remains both a challenge and a rate-limiting step in enzyme discovery. Biocatalytic strategies for the synthesis of chiral amines are increasingly attractive and include enzymatic asymmetric reductive amination, which offers an efficient route to many of these high-value compounds. Here we report the discovery of over 300 new imine reductases and the production of a large (384 enzymes) and sequence-diverse panel of imine reductases available for screening. We also report the development of a facile high-throughput screen to interrogate their activity. Through this approach we identified imine reductase biocatalysts capable of accepting structurally demanding ketones and amines, which include the preparative synthesis of N-substituted β-amino ester derivatives via a dynamic kinetic resolution process, with excellent yields and stereochemical purities. [Figure not available: see fulltext.]
CHIRALITY SENSING WITH MOLECULAR CLICK CHEMISTRY PROBES
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, (2020/02/23)
The present invention relates to an analytical method that includes providing a sample potentially containing a chiral analyte that can exist in stereoisomeric forms, and providing a probe selected from the group consisting of coumarin-derived Michael acceptors, dinitrofluoroarenes and analogs thereof, arylsulfonyl chlorides and analogs thereof, arylchlorophosphines and analogs thereof, aryl halophosphites, and halodiazaphosphites. The sample is contacted with the probe under conditions to permit covalent binding of the probe to the analyte, if present in the sample; and, based on any binding that occurs, the absolute configuration of the analyte in the sample, and/or the concentration of the analyte in the sample, and/or the enantiomeric composition of the analyte in the sample is/are determined. The probe may be a coumarin-derived Michael acceptor, a di nitrofluoroarene or analog thereof, an arylsulfonyl chloride or analog thereof, an arylchlorophosphine or analog thereof, an aryl halophosphite, or a halodiazaphosphite.
Direct Asymmetric Hydrogenation of N-Methyl and N-Alkyl Imines with an Ir(III)H Catalyst
Salomó, Ernest,Gallen, Albert,Sciortino, Giuseppe,Ujaque, Gregori,Grabulosa, Arnald,Lledós, Agustí,Riera, Antoni,Verdaguer, Xavier
supporting information, p. 16967 - 16970 (2018/12/14)
A novel cationic [IrH(THF)(P,N)(imine)] [BArF] catalyst containing a P-stereogenic MaxPHOX ligand is described for the direct asymmetric hydrogenation of N-methyl and N-alkyl imines. This is the first catalytic system to attain high enantioselectivity (up to 94% ee) in this type of transformation. The labile tetrahydrofuran ligand allows for effective activation and reactivity, even at low temperatures. Density functional theory calculations allowed the rationalization of the stereochemical course of the reaction.
A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines
Jolley, Katherine E.,Chapman, Michael R.,John Blacker
supporting information, p. 2220 - 2228 (2018/09/04)
Chloramines are an important class of reagents, providing a convenient source of chlorine or electrophilic nitrogen. However, the instability of these compounds is a problem which makes their isolation and handling difficult. To overcome these hazards, a continuous-flow approach is reported which generates and immediately reacts N-chloramines directly, avoiding purification and isolation steps. 2-Chloramines were produced from the reaction of styrenes with N-alkyl-N-sulfonyl-N-chloramines, whilst N-alkyl or N,N’-dialkyl-N-chloramines reacted with anisaldehyde in the presence of t-BuO2H oxidant to afford amides. Primary and secondary imines were produced under continuous conditions from the reaction of N-chloramines with base, with one example subsequently reduced under asymmetric conditions to produce a chiral amine in 94% ee.
Selective Monomethylation of Amines with Methanol as the C1 Source
Choi, Geunho,Hong, Soon Hyeok
supporting information, p. 6166 - 6170 (2018/04/30)
The N-monomethyl functionality is a common motif in a variety of synthetic and natural compounds. However, facile access to such compounds remains a fundamental challenge in organic synthesis owing to selectivity issues caused by overmethylation. To address this issue, we have developed a method for the selective, catalytic monomethylation of various structurally and functionally diverse amines, including typically problematic primary aliphatic amines, using methanol as the methylating agent, which is a sustainable chemical feedstock. Kinetic control of the aliphatic amine monomethylation was achieved by using a readily available ruthenium catalyst at an adequate temperature under hydrogen pressure. Various substrates including bio-related molecules and pharmaceuticals were selectively monomethylated, demonstrating the general utility of the developed method.
Imine Reductase-Catalyzed Intermolecular Reductive Amination of Aldehydes and Ketones
Scheller, Philipp N.,Lenz, Maike,Hammer, Stephan C.,Hauer, Bernhard,Nestl, Bettina M.
, p. 3239 - 3242 (2015/10/28)
Imine reductases (IREDs) have emerged as promising biocatalysts for the synthesis of chiral amines. In this study, the asymmetric imine reductase-catalyzed intermolecular reductive amination with NADPH as the hydrogen source was investigated. A highly chemo- and stereoselective imine reductase was applied for the reductive amination by using a panel of carbonyls with different amine nucleophiles. Primary and secondary amine products were generated in moderate to high yields with high enantiomeric excess values. The formation of the imine intermediate was studied between carbonyl substrates and methylamine in aqueous solution in the pH range of 4.0 to 9.0 by 1H NMR spectroscopy. We further measured the kinetics of the reductive amination of benzaldehyde with methylamine. This imine reductase-catalyzed approach constitutes a powerful and direct method for the synthesis of valuable amines under mild reaction conditions. IRED all about it: The intermolecular asymmetric reductive amination of carbonyls catalyzed by a stereoselective imine reductase produces chiral amines in high yields with high enantioselectivities. The reaction efficiency is attributed to its remarkable tolerance to high concentrations of amine nucleophiles, high pH values, high chemoselectivity towards imines, and high stereoselectivity of the biocatalyst.
Chiral molecular tweezers: Synthesis and reactivity in asymmetric hydrogenation
Lindqvist, Markus,Borre, Katja,Axenov, Kirill,Kótai, Bianka,Nieger, Martin,Leskel?, Markku,Pápai, Imre,Repo, Timo
supporting information, p. 4038 - 4041 (2015/04/14)
We report the synthesis and reactivity of a chiral aminoborane displaying both rapid and reversible H2 activation. The catalyst shows exceptional reactivity in asymmetric hydrogenation of enamines and unhindered imines with stereoselectivities of up to 99% ee. DFT analysis of the reaction mechanism pointed to the importance of both repulsive steric and stabilizing intermolecular non-covalent forces in the stereodetermining hydride transfer step of the catalytic cycle.
Disulfonimide-Catalyzed Asymmetric Reduction of N-Alkyl Imines
Wakchaure, Vijay N.,Kaib, Philip S. J.,Leutzsch, Markus,List, Benjamin
supporting information, p. 11852 - 11856 (2015/10/05)
A chiral disulfonimide (DSI)-catalyzed asymmetric reduction of N-alkyl imines with Hantzsch esters as a hydrogen source in the presence of Boc2O has been developed. The reaction delivers Boc-protected N-alkyl amines with excellent yields and enantioselectivity. The method tolerates a large variety of alkyl amines, thus illustrating potential for a general reductive cross-coupling of ketones with diverse amines, and it was applied in the synthesis of the pharmaceuticals (S)-Rivastigmine, NPS R-568 Hydrochloride, and (R)-Fendiline. A chiral disulfonimide (DSI)-catalyzed asymmetric reduction of N-alkyl imines with Hantzsch esters as a hydrogen source in the presence of Boc2O was developed. The reaction delivers Boc-protected N-alkyl amines with excellent yields and enantioselectivity. The method was successfully applied to the synthesis of the pharmaceuticals (S)-Rivastigmine, NPS R-568 Hydrochloride, and (R)-Fendiline.
Synthesis and characterization of chiral guanidines und guanidinium salts derived from 1-phenylethylamine
Castiglia, Amelie,El Sehrawi, Hend M.,Orbegozo, Thomas,Spitzner, Dietrich,Claasen, Birgit,Frey, Wolfgang,Kantlehner, Willi,Jaeger, Volker
body text, p. 337 - 346 (2012/07/14)
The synthesis of two new chiral guanidines 5 and 12 and derived guanidinium salts 6, 11, 13 -15 with one and three N-(1-phenylethyl) substituents is described. In both cases, the well-precedented, reliable route via chloro-formamidines was taken. Since di
