5933-40-4Relevant academic research and scientific papers
Synthesis of limonene β-amino alcohol from (R)-(+)-α-methylbenzylamine and (+)-limonene 1,2-epoxide
Ait Said, Lyazid,El Bachiri, Abdelhadi,El Haimer, Chaimaa,El Hammoumi, Mohamed Merouane,Khoukhi, Mostafa
, (2021/06/02)
Two new compounds of β-amino alcohol are obtained using (R) - (+) - α-methylbenzylamine as starting material which is converted into two amines. Each of these compounds reacted in excess with a 1: 1 mixture of cis and trans-limonene oxide in the presence of water as a catalyst. The products obtained show that β-amino alcohol derived from trans-limonene oxide is obtained and unreacted cis-limonene oxide from the reaction mixture as well as the amine is attained. Whereas the addition of the synthesized carbamate of the same primary amine over the 1: 1 mixture of cis and trans -limonene oxide in the presence of water results in the hydrolysis product and the recovery of unreacted trans-limonene oxide.
Deactivation mechanisms of iodo-iridium catalysts in chiral amine racemization
Kwan, Maria H.T.,Pokar, Nisha P.B.,Good, Catherine,Jones, Martin F.,Munday, Rachel,Screen, Thomas,Blacker, A. John
supporting information, (2020/12/29)
The homogenous, [IrCp?I2]2, SCRAM catalyst (1) is active in the racemization of chiral amines. NMR, kinetic and structural mechanistic studies have determined the cause of catalyst deactivation to occur when ammonia or methylamine are liberated by hydrolysis or aminolysis of the intermediate imine, which tightly coordinate to the iridium centre to block turnover. Control of moisture and substrate concentration can suppress deactivation, whilst partial reactivation of spent catalyst was identified using hydroiodic acid.
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.]
Tackling N-Alkyl Imines with 3d Metal Catalysis: Highly Enantioselective Iron-Catalyzed Synthesis of α-Chiral Amines
Blasius, Clemens K.,Gade, Lutz H.,Heinrich, Niklas F.,Vasilenko, Vladislav
, p. 15974 - 15977 (2020/07/04)
A readily activated iron alkyl precatalyst effectively catalyzes the highly enantioselective hydroboration of N-alkyl imines. Employing a chiral bis(oxazolinylmethylidene)isoindoline pincer ligand, the asymmetric reduction of various acyclic N-alkyl imines provided the corresponding α-chiral amines in excellent yields and with up to >99 % ee. The applicability of this base metal catalytic system was further demonstrated with the synthesis of the pharmaceuticals Fendiline and Tecalcet.
Asymmetric Synthesis of Primary and Secondary β-Fluoro-arylamines using Reductive Aminases from Fungi
González-Martínez, Daniel,Cuetos, Aníbal,Sharma, Mahima,García-Ramos, Marina,Lavandera, Iván,Gotor-Fernández, Vicente,Grogan, Gideon
, p. 2421 - 2425 (2020/03/25)
The synthesis of chiral amines is of central importance to pharmaceutical chemistry, and the inclusion of fluorine atoms in drug molecules can both increase potency and slow metabolism. Optically enriched β-fluoroamines can be obtained by the kinetic resolution of racemic amines using amine transaminases (ATAs), but yields are limited to 50 %, and also secondary amines are not accessible. In order to overcome these limitations, we have applied NADPH-dependent reductive aminase enzymes (RedAms) from fungal species to the reductive amination of α-fluoroacetophenones with ammonia, methylamine and allylamine as donors, to yield β-fluoro primary or secondary amines with >90 % conversion and between 85 and 99 % ee. In addition, the effect of the progressive introduction of fluorine atoms to the α-position of the acetophenone substrate reveals the effect of mono-, di- and tri-fluorination on the proportion of amine and alcohol in product mixtures, shedding light on the promiscuous ability of imine reductase (IRED)-type dehydrogenases to reduce fluorinated acetophenones to alcohols.
CHIRALITY SENSING WITH MOLECULAR CLICK CHEMISTRY PROBES
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Paragraph 0237; 0243-0244; 0285-0287, (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.
Secondary amines as coupling partners in direct catalytic asymmetric reductive amination
Wu, Zitong,Du, Shaozhi,Gao, Guorui,Yang, Wenkun,Yang, Xiongyu,Huang, Haizhou,Chang, Mingxin
, p. 4509 - 4514 (2019/04/29)
The secondary amine participating asymmetric reductive amination remains an unsolved problem in organic synthesis. Here we show for the first time that secondary amines are capable of effectively serving as N-sources in direct asymmetric reductive amination to afford corresponding tertiary chiral amines with the help of a selected additive set under mild conditions (0-25 °C). The applied chiral phosphoramidite ligands are readily prepared from BINOL and easily modified. Compared with common tertiary chiral amine synthetic methods, this procedure is much more concise and scalable, as exemplified by the facile synthesis of rivastigmine and N-methyl-1-phenylethanamine.
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
, 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.
Stereogenic Lock in 1-Naphthylethanamine Complexes for Catalyst and Auxiliary Design: Structural and Reactivity Analysis for Cycloiridated Pseudotetrahedral Complexes
Chen, Houguang Jeremy,Hong Xiang Teo, Ronald,Li, Yongxin,Pullarkat, Sumod A.,Leung, Pak-Hing
supporting information, p. 99 - 106 (2018/01/17)
A series of optically active pseudo-tetrahedral five-membered cyclometalated 1-naphthylethanamine iridium(III) complexes were prepared and characterized to analyze the efficacy of the stereogenic conformational lock in both solid and solution phases. The synthesis of the iridacycles was diastereoselective, and the compounds were found to be conformationally rigid. In comparison to its phenyl derivative, the structural lock prevented oxidation of the amine moiety within the five-membered organometallic ring during its synthesis. With up to three stereogenic centers in one of the naphthalene complexes, the stereochemistry of the metallacycle remained stable to both thermal and chemical changes. In terms of catalytic performance, the complexes displayed excellent activity for the asymmetric hydrogen transfer reaction, albeit with modest enantioselectivities.
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.
