66896-61-5Relevant academic research and scientific papers
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.]
Selective hydrosilylation of N-allylimines using a (3-iminophosphine)palladium precatalyst
Tafazolian, Hosein,Schmidt, Joseph A.R.
, p. 685 - 689 (2016/02/18)
Hydrosilylation utilizing a (3-iminophosphine)palladium catalyst leads to the selective reduction of the imine unit of allylimines. Successful reduction of twenty-five different substituted aromatic and alkyl allylimines demonstrated the scope and selecti
Rhodium-Catalyzed Regiodivergent Hydrothiolation of Allyl Amines and Imines
Kennemur, Jennifer L.,Kortman, Gregory D.,Hull, Kami L.
supporting information, p. 11914 - 11919 (2016/10/06)
The regiodivergent Rh-catalyzed hydrothiolation of allyl amines and imines is presented. Bidentate phosphine ligands with larger natural bite angles (βn ≥ 99°), for example, DPEphos, dpph, or L1, promote a Markovnikov-selective hydrothiolation in up to 88% yield and >20:1 regioselectivity. Conversely, when smaller bite angle ligands (βn ≤ 86°), for example, dppbz or dppp, are employed, the anti-Markovnikov product is formed in up to 74% yield and >20:1 regioselectivity. Initial mechanistic investigations are performed and are consistent with an oxidative addition/olefin insertion/reductive elimination mechanism for each regioisomeric pathway. We hypothesize that the change in regioselectivity is an effect of diverging coordination spheres to favor either Rh-S or Rh-H insertion to form the branched or linear isomer, respectively.
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.
Mild nonepimerizing N -alkylation of amines by alcohols without transition metals
Guerin, Claire,Bellosta, Veronique,Guillamot, Gerard,Cossy, Janine
supporting information; experimental part, p. 3534 - 3537 (2011/08/10)
A one-pot two-step sequence involving an oxidation/imine-iminium formation/reduction allowed the N-alkylation of amines by alcohols without any epimerization when optically active alcohols and amines are involved in the process.
One-pot amide synthesis from allyl or benzyl halides and amines by Pd-catalysed carbonylation
Troisi, Luigino,Granito, Catia,Rosato, Francesca,Videtta, Valeria
experimental part, p. 371 - 373 (2010/03/24)
Amides can be prepared from allyl or benzyl halides and primary or secondary amines, using Pd(0) catalyst under CO pressure, in a one-pot synthesis. The reaction proceeds through the acyl palladium halide formation which undergoes an acylic nucleophilic substitution from the amine.
A highly enantioselective organocatalytic method for reduction of aromatic N-alkyl ketimines
Wang, Chao,Wu, Xinjun,Zhou, Li,Sun, Jian
supporting information; experimental part, p. 8789 - 8792 (2009/09/25)
A study has demonstrated the development of a highly enantioselective catalytic method for the reduction of aromatic N-alkyl ketimines by trichlorosilane under mild conditions using the newly designed Lewis base organocatalyst that incorporates C- and S-chirality. The S-chiral sulfinamide group in these catalysts plays a crucial role similar to the carboxamide groups as Lewis base for the activation of HSiCl3, and also serves as a source of chirality that the carboxamide group lacks for the asymmetric induction. The results of the study showed that excellent enantioselectivities of up to 99.6% ee and high yields were obtained for a wide range of substrates. Further works is also in progress to clarify the mechanism of the transformation and explore the full application scope of the present catalyst system.
Why platinum catalysts involving ligands with large bite angle are so efficient in the allylation of amines: Design of a highly active catalyst and comprehensive experimental and DFT study
Mora, Guilhem,Piechaczyk, Olivier,Houdard, Romaric,Mezailles, Nicolas,Le Goff, Xavier-Frederic,Le Floch, Pascal
experimental part, p. 10047 - 10057 (2009/11/30)
The platinum-catalyzed allylation of amines with allyl alcohols was studied experimentally and theoretically. The complexes [Pt(η3-allyl)- (dppe)]OTf (2) and [Pt(η3-allyl)(DPP-Xantphos)]PF6 (5) were synthesized and structurally characterized, and their reactivity toward amines was explored. The bicyclic aminopropyl complex [Pt(CH2CH 2CH2NHBn-κ-C,N)-(dppe)]OTf (3) was obtained from the reaction of complex 2 with an excess of benzylamine, and this complex was shown to be a deactivated form of catalyst 2. On the other hand, reaction of complex 5 with benzylamine and allyl alcohol led to formation of the 16-VE platinum(0) complex [P(η2-C3H3OH)-(DPP-Xantphos)] (7), which was structurally characterized and appears to be a catalytic intermediate. A DFT study showed that the mechanism of the platinum-catalyzed allylation of amines with allyl alcohols differs from the palladium-catalyzed process, since it involves an associative ligand-exchange step involving formation of a tetracoordinate 18-VE complex. This DFT study also revealed that ligands with large bite angles disfavor the formation of platinum hydride complexes and therefore the formation of a bicyclic aminopropyl complex, which is a thermodynamic sink. Finally, a combination of 5 and a proton source was shown to efficiently catalyze the allylation of a broad variety of amines with allyl alcohols under mild conditions.
The [2,3] sigmatropic rearrangement of N-benzyl-O-allylhydroxylamines
Davies, Stephen G.,Fox, John F.,Jones, Simon,Price, Anne J.,Sanz, Miguel A.,Sellers, Thomas G. R.,Smith, Andrew D.,Teixeira, Fatima C.
, p. 1757 - 1765 (2007/10/03)
The rearrangement of a range of N-benzyl-O-allylhydroxylamines to the corresponding N-allylhydroxylamines upon treatment with n-BuLi in THF, followed by reduction to the corresponding N-allylamines, is described. Mechanistic studies of the transformation are consistent with an intramolecular [2,3] sigmatropic rearrangement.
