Synthesis
Reported synthetic methods fall into two categories: one involves the direct reaction of L-alanine, L-alanine hydrochloride, or L-alanine methyl ester with phenyl magnesium bromide to prepare (S)-2-amino-1,1-diphenyl-1-propanol. However, this method suffers from complex products, difficult purification, and low yields. The other method uses L-alanine as a starting material and involves a four-step reaction: methyl ester of L-2-benzylcarbonylaminoalanine, obtained through methylation and benzyloxycarbonyl protection, reacts with phenyl magnesium bromide to obtain (S)-benzyloxycarbonylamino-1,1-diphenyl-1-propanol, which is then catalytically hydrogenated to remove the benzyloxycarbonyl group, yielding (S)-2-amino-1,1-diphenyl-1-propanol. This paper reports a novel method for synthesizing (S)-2-amino-1,1-diphenyl-1-propanol.
In the presence of potassium carbonate and using water-ethanol as a mixed solvent, the amino and carboxyl groups of L-alanine molecule react simultaneously with benzyl chloride to generate N,N-dibenzyl-L-alanine benzyl ester (1); 1 reacts with magnesium phenyl bromide via a Grignard reaction to give 1,1-diphenyl-2-(N,N-dibenzylamino)-1-propanol (2); 2 is deprotected by Pd/C catalytic hydrogenation to obtain 3, with an overall yield of 48.1%. The intermediate and target products of this synthetic method are easily separated and purified. The synthetic reaction formula of (S)-2-amino-1,1-diphenyl-1-propanol is shown in the figure below:
Application
In asymmetric synthesis, the synthesis of chiral catalysts or chiral auxiliaries is crucial. Chiral amino alcohols are widely used as ligands or catalysts for catalyzing asymmetric synthetic reactions and are also important precursors for the synthesis of many chiral drugs, natural products, and chemical and biological functional materials. (S)-2-amino-1,1-diphenyl-1-propanol belongs to the optically active β-amino alcohols. It can be used for asymmetric reduction of pre-chiral ketones, asymmetric catalytic epoxidation reactions, and asymmetric catalytic alkylation reactions of carbonyl compounds. (S)-2-amino-1,1-diphenyl-1-propanol has also been reported as an intermediate in the synthesis of chiral complexes in asymmetric cyclopropanation reactions.
