2163-33-9Relevant academic research and scientific papers
Ni-Catalyzed reductive amination of phenols with ammonia or amines into cyclohexylamines
Cuypers, Thomas,Morias, Thomas,Windels, Simon,Marquez, Carlos,Van Goethem, Cédric,Vankelecom, Ivo,De Vos, Dirk E.
, p. 1884 - 1893 (2020/04/07)
Phenol and its derivatives, which naturally occur in lignocellulose, can be considered as a renewable feedstock not only for aromatic, but also for alicyclic compounds, such as primary and N-substituted cyclohexylamines. So far, the latter are mostly produced from non-renewable starting materials like benzene via problematic nitration/reduction or cross-coupling routes. Herein, an efficient reductive amination of phenol with ammonia or amines is demonstrated, for the first time without the need for rare and expensive noble metals and without using any additives. Various supported Ni catalysts were screened and we elucidated the influence of the key parameters, including the acid-base properties of the supporting material. Acquired knowledge was then applied to different phenol-ammonia/amine combinations, resulting in the synthesis of various primary, secondary and tertiary cyclohexylamines in fair to very high yields.
Application of Transaminases in a Disperse System for the Bioamination of Hydrophobic Substrates
Berglund, Per,Fiorati, Andrea,Humble, Maria S.,Tessaro, Davide
, (2020/02/04)
The challenging bioamination of hydrophobic substrates has been attained through the employment of a disperse system consisting of a combination of a low polarity solvent (e. g. isooctane or methyl-tert-butylether), a non-ionic surfactant and a minimal amount of water. In these conditions, amine transaminases (ATA) were shown to efficiently carry out the reductive amination of variously substituted cyclohexanones, providing good conversions often coupled with a superior stereoselectivity if compared with the corresponding chemical reductive amination. An array of synthetically useful 4-substituted aminocyclohexanes was consequentially synthesized through biocatalysis, analyzed and stereochemically characterized. (Figure presented.).
Discovery and Optimization of a Compound Series Active against Trypanosoma cruzi, the Causative Agent of Chagas Disease
Harrison, Justin R.,Sarkar, Sandipan,Hampton, Shahienaz,Riley, Jennifer,Stojanovski, Laste,Sahlberg, Christer,Appelqvist, Pia,Erath, Jessey,Mathan, Vinodhini,Rodriguez, Ana,Kaiser, Marcel,Pacanowska, Dolores Gonzalez,Read, Kevin D.,Johansson, Nils Gunnar,Gilbert, Ian H.
, p. 3066 - 3089 (2021/06/14)
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in South and Central America and recently has been found in other parts of the world, due to migration of chronically infected patients. The current treatment for Chagas disease is not satisfactory, and there is a need for new treatments. In this work, we describe the optimization of a hit compound resulting from the phenotypic screen of a library of compounds against T. cruzi. The compound series was optimized to the level where it had satisfactory pharmacokinetics to allow an efficacy study in a mouse model of Chagas disease. We were able to demonstrate efficacy in this model, although further work is required to improve the potency and selectivity of this series.
Reductive amination of ketonic compounds catalyzed by Cp*Ir(III) complexes bearing a picolinamidato ligand
Tanaka, Kouichi,Miki, Takashi,Murata, Kunihiko,Yamaguchi, Ayumi,Kayaki, Yoshihito,Kuwata, Shigeki,Ikariya, Takao,Watanabe, Masahito
, p. 10962 - 10977 (2019/09/03)
Cp*Ir complexes bearing a 2-picolinamide moiety serve as effective catalysts for the direct reductive amination of ketonic compounds to give primary amines under transfer hydrogenation conditions using ammonium formate as both the nitrogen and hydrogen source. The clean and operationally simple transformation proceeds with a substrate to catalyst molar ratio (S/C) of up to 20,000 at relatively low temperature and exhibits excellent chemoselectivity toward primary amines.
Aliphatic C-H Bond Oxidation with Hydrogen Peroxide Catalyzed by Manganese Complexes: Directing Selectivity through Torsional Effects
Milan, Michela,Bietti, Massimo,Costas, Miquel
supporting information, p. 2720 - 2723 (2018/05/22)
Substituted N-cyclohexyl amides undergo aliphatic C-H bond oxidation with H2O2 catalyzed by manganese complexes. The reactions are directed by torsional effects leading to site-selective oxidation of cis-1,4-, trans-1,3-, and cis-1,2-cyclohexanediamides. The corresponding diastereoisomers are unreactive under the same conditions. Competitive oxidation of cis-trans mixtures of 4-substituted N-cyclohexylamides leads to quantitative conversion of the cis-isomers, allowing isolation and successive conversion of the trans-isomers into densely functionalized oxidation products with excellent site selectivity and good enantioselectivity.
HIGHLY STEREOSELECTIVE SYNTHESIS OF CYCLIC PRIMARY AMINES VIA HYDRIDE REDUCTIONS.
Hutchins, Robert O.,Su, Wei-Yang
, p. 695 - 698 (2007/10/02)
The reduction of p,p'-dimethoxybenzhydryl imines of substituted cyclohexanones with lithium tri-sec-butyl or tri-ethylborohydride and subsequent cleavage of the resulting secondary amines with formic acid affords the corresponding axial cyclohexyl primary amines with high stereoselectivity.
Reduction of Oximes with Sodium Borohydride in the Presence of Transition Metal Compounds
Ipaktschi, Junes
, p. 856 - 858 (2007/10/02)
The reduction of oximes with sodium borohydride in the presence of NiCl2 * 6 H2O and MoO3 was investigated.The combination of NaBH4 with NiCl2 * 6 H2O converted the unsaturated oximes through exhaustive reduction into saturated amines (Table 1).The C = C double bond remains preserved if the reduction is carried out in the presence of MoO3 (Table 2).The stereochemistry of the reduction in the presence of NiCl2 * 6 H2O is distinctivly different from that of MoO3.
Stereoselective Reductions of Substituted Cyclohexyl and Cyclopentyl Carbon-Nitrogen ? Systems with Hydride Reagents
Hutchins, Robert O.,Su, Wei-Yang,Sivakumar, Ramachandran,Cistone, Frank,Stercho, Yuriy P.
, p. 3412 - 3422 (2007/10/02)
Reductions of 3- and 4-substituted cyclohexyl imines, iminium salts, and enamines (via iminium ions) with various hydride reagents reveal that while small reagents (NaBH4, NaBH3CN) favor axial approach as observed with the corresponding ketones, even moderately bulky reagents (i.e., acetoxyboranes) attack preferentially from the equatorial side.This is in direct contrast to the results observed for the same reagents with the corresponding ketones and is interpreted as implying that additional steric interactions induced by the nitrogen substituents encumber axial attack by substituted hydride reagents and force approach from the equatorial direction.The very bulky tri-sec-butylborohydride anion affords highly stereodiscriminating equatorial attack.Reductions of 2-alkylcyclohexyl and 2-alkylcyclopentyl imines and enamines also proceed with high stereoselectivity to give cis-2-alkyl cyclic amines with both hindered and unhindered reagents.This is interpreted to be the result of (1) augmented steric interactions between nitrogen substituents and equatorial 2-alkyl groups (1,3-allylic strain) which induces conformational changes to favor the axial 2-alkyl conformer and (2) hindrance toward equatorial approach by reagents induced by axial alkyl substituents.The result is that equatorial approach is favored with equatorial 2-alkyl conformers and preferential axial approach with axial 2-alkyl conformers, leading to stereoselective production of cis-2-alkylamines. trans-2-n-Propyl-4-tert-butylcyclohexanone is reduced by LiBH(sec-Bu)3 preferentially from the axial direction in contrast to the usual highly selective equatorial attack observed with other cyclohexanones.
