Oxa-Michael Addition to alpha,beta-Unsaturated Nitriles: An Expedient Route to gamma-Amino Alcohols and Derivatives

Beibei Guo, Douwe S. Zijlstra, Johannes G. de Vries*, Edwin Otten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)
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Abstract

Water addition to alpha,beta-unsaturated nitriles would give facile access to the -hydroxy-nitriles, which in turn can be hydrogenated to the gamma-amino alcohols. We have previously shown that alcohols readily add in 1,4-fashion to these substrates using Milstein's Ru(PNN) pincer complex as catalyst. However, attempted water addition to alpha,beta-unsaturated nitriles gave the 3-hydroxynitriles in mediocre yields. On the other hand, addition of benzyl alcohol proceeded in excellent yields for a variety of -substituted unsaturated nitriles. Subsequent treatment of the benzyl alcohol addition products with TMSCl/FeCl3 resulted in the formation of 3-hydroxy-alkylnitriles. The 3-benzyloxy-alkylnitriles obtained from oxa-Michael addition also could be hydrogenated directly in the presence of acid to give the amino alcohols as their HCl salts in excellent yields. Hydrogenation under neutral conditions gave a mixture of the secondary and tertiary amines. Hydrogenation in the presence of base and Boc-anhydride gave the orthogonally bis-protected amino alcohols, in which the benzyl ether can subsequently be cleaved to yield Boc-protected amino alcohols. Thus, a variety of molecular scaffolds with a 1,3-relationship between O- and N-functional group is accessible starting from oxa-Michael addition of benzyl alcohol to alpha,beta-unsaturated nitriles.

Original languageEnglish
Pages (from-to)2868-2872
Number of pages5
JournalChemCatChem
Volume10
Issue number13
DOIs
Publication statusPublished - 9-Jul-2018

Keywords

  • oxa-Michael addition
  • amino alcohols
  • hydrogenation
  • nitriles
  • pincer ligand
  • ruthenium
  • ENANTIOSELECTIVE BETA-BORYLATION
  • REDOX-FLOW BATTERY
  • TRIETHANOLAMINE STEARATE
  • UNSATURATED NITRILES
  • CARBOXYLIC-ACIDS
  • LIGAND
  • WATER
  • ACCEPTORS
  • COMPLEX
  • HYDROGENATION

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