An efficient enantioselective synthesis of (S)-α-methyl-serine methyl ester hydrochloride via asymmetrically catalyzed amination

Abstract

We present the synthesis of enantiomerically pure (S)-α-methyl-serine methyl ester hydrochloride from 2-methyl-3-((4-(trifluoromethyl)benzyl)oxy)propanal and di-p-chlorobenzyl azodicarboxylate via asymmetrically catalyzed amination with naphthylalanine derivative catalyst. The application of the organocatalyst of D-3-(1-Naphthyl)-alanine is the key step in the synthesis and ensures the product is obtained with high levels of stereocontrol.

Graphical Abstract

Keywords:

• Asymmetric Michael α-amination
• α-methyl-α-protected hydroxymethyl aldehydes
• one-pot protocol
• (S)-α-methyl-serine

Additional information

Funding

This work was financially supported by the Drug Innovation Major Project (No. 2018ZX09711001-005-012), National Key R&D Program of China (No. 2018YFC1706403) and CAMS Innovation Fund for Medical Sciences (No. 2016-I2M-2-002).