Stereoselective Synthesis of 3-Hydroxyproline Benzyl Esters fromN-Protected β-Aminoaldehydes and Benzyl Diazoacetate

  • 10.1021/jo030360f
  • The Journal of Organic Chemistry
  • p 4361-4368, Volume 69, Issue 13,
  • journal-article
The synthesis of a series of 3-hydroxyproline benzyl esters from α-alkyl and α-alkoxy N-protected aminoaldehydes with benzyl diazoacetate is described. Aldehydes with α-alkyl substituents afforded prolines as a single diastereomer with a trans-cis relative configuration in 14−77%. An α-tert-butyldimethylsilyloxy aminoaldehyde afforded a proline as a single diastereomer with a trans-trans relative configuration in 37% yield.


Adaptations Necessary to Improve Published Syntheses

This review addresses the published preparation of compound 10c as listed in JOC 69, 4361 (2004).  The stated preparation utilizes the inexpensive, commercially available diol, 6c.  The preparation begins by combining the diol with one equivalent of TESCl in the presence of...