Studies on N‐Activation for the Lipase‐Catalyzed Enantioselective Preparation of β‐Amino Esters from 4‐Phenylazetidin‐2‐one

• Published in: European Journal of Organic Chemistry
• Main Authors: Sundell, Riku, Kanerva, Liisa T.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2015
• Subjects: Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/ejoc.201403467; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fejoc.201403467; http://onlinelibrary.wiley.com/wol1/doi/10.1002/ejoc.201403467/fullpdf

Abstract The effect of N ‐substitution was examined for the enantioselective lipase‐catalyzed ring‐opening reaction of racemic 4‐phenylazetidin‐2‐one with methanol in dry organic solvents. Marked differences in the reactivity of various N ‐protected 4‐phenylazetidin‐2‐ones were observed. Preparative‐scale reactions with Candida antarctica lipase B (Novozym 435 preparation) yielded N ‐acylated methyl ( R )‐3‐amino‐3‐phenylpropanoates with enantiomeric excess ( ee ) values >99 % in up to a 49 % isolated yield, whereas Thermomyces lanuginosus lipase (Lipozyme TM IM) gave enantiomerically enriched methyl ( S )‐3‐acetamido‐3‐phenylpropanoate. Candida antarctica lipase A catalyzed the cleavage of the N ‐chloroacetyl protective group, whereas all of the other examined lipases underwent the ring‐opening reaction.