26191-38-8

Upstream product

• 93-88-9 phenpromethamine 
• 270258-71-4 (R)-N-methyl-2-phenylpropionamide 
• 7782-26-5 (R)-2-Phenylpropionic acid 
• 34713-70-7 2-Phenylpropanal 
• 160247-37-0 N-[(R)-2-hydroxy-1-phenylethyl]-N-methyl-2-phenylacetamide 
• 74-89-5 methylamine 
• 36240-11-6 (R)-(-)-2-phenylpropionyl chloride 

Relevant academic research and scientific papers

Synthesis of β-Chiral Amines by Dynamic Kinetic Resolution of α-Branched Aldehydes Applying Imine Reductases

Imine reductases (IREDs) allow the one-step preparation of optically active secondary and tertiary amines by reductive amination of ketones. Until now, mainly α-chiral amines have been prepared by this route. In this study, we explored the possibility of synthesizing β-chiral amines, a class of compounds which is also frequently found as structural motif in pharmaceuticals but much more challenging to prepare due to the following reasons: (i) The aldehyde substrate already contains the chiral center and needs to be racemized to enable full conversion. (ii) Because the intermediate imine bears the stereo center two carbon atoms remote to the imine nitrogen, it is more challenging to achieve high enantioselectivity compared to α-chiral amine synthesis. For investigating the proof of concept, we first confirmed that different IREDs are able to convert a variety of α-branched aldehydes when combined with five different amine substrates. The IRED from Streptomyces ipomoeae was a suitable enzyme facilitating the dynamic kinetic resolution of 2-phenylpropanal and a substituted 2-methyl-3-phenylpropanal: the corresponding N-methylated β-chiral amines were obtained with '95 % conversion and 78 and 95 %ee. Other amines were formed with low to moderate enantiomeric excess. This exemplifies the potential of IREDs for the one-step synthesis of secondary β-chiral amines, but also the challenge to identify highly selective enzymes for a desired amine product.

The ruthenium-catalyzed reduction and reductive N-alkylation of secondary amides with hydrosilanes: Practical synthesis of secondary and tertiary amines by judicious choice of hydrosilanes

(Chemical Equation Presented) A triruthenium cluster, (μ3, η2,η3,η5-acenaphthylene)Ru 3(CO)7 (1) catalyzes the reaction of secondary amides with hydrosilanes, yielding a mixture of secondary amines, tertiary amines, and silyl enamines. Production of secondary amines with complete selectivity is achieved by the use of higher concentration of the catalyst (3 mol %) and the use of bifunctional hydrosilanes such as 1,1,3,3-tetramethyldisiloxane. Acidic workup of the reaction mixture affords the corresponding ammonium salts, which can be treated with a base, providing a facile method for isolation of secondary amines with high purity. In contrast, tertiary amines are formed with high selectivity by using lower concentration of the catalyst (1 mol %) and polymeric hydrosiloxanes (PMHS) as reducing agent. Reduction with PMHS encapsulates the ruthenium catalyst and organic byproducts to the insoluble silicone resin. The two reaction manifolds are applicable to various secondary amides and are practical in that the procedures provide the desired secondary or tertiary amine as a single product. The product contaminated with only minimal amounts of ruthenium and silicon residues. On the basis of the products and observed side products as well as NMR studies a mechanistic scenario for the reaction is also described.

The stereoselectivity of inhibition of rat liver mitochondrial MAO-A and MAO-B by the enantiomers of 2-phenylpropylamine and their derivatives

As part of a study of the stereoselectivity of inhibition of the different forms of monoamine oxidase (MAO-A and MAO-B), the enantiomers of 2- phenylpropylamine, N-methyl-2-phenylpropylamine and N-methyl-N-propargyl-2- phenylpropylamine have been prepared. The K(i) values for each enantiomer when competitively inhibiting both MAO-A and MAO-B are reported. The enantiomers of N-methyl-N-propargyl-2-phenylpropylamine were also evaluated as irreversible inhibitors (first order rate constant [k2] for formation of the covalent adduct). These compounds represent a series of enantiomers in which asymmetry is due to the presence of a hydrophobic (-CH3) substituent at the carbon atom β to the amino function. The results are discussed in comparison to previous studies of similar enantiomeric compounds in which the asymmetry was present at the carbon atom α to the amino function.

Enantioselective synthesis of β-substituted primary and secondary amines by alkylation of (R)-phenylglycinol amide enolates

General and convenient syntheses of optically active β-substituted secondary or primary amines 4 and 8 are described. The method is based on diastereoselective alkylation of amides 1 and 5 derived from R-(-)-phenylglycinol followed by reduction and removal of the chiral appendage. This procedure has also been applied to the preparation of 1,4-amino alcohols 12 and γ-amino esters 14.