Strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays based on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides: application to natural product synthesis

Chemistry. 2004 Mar 19;10(6):1527-44. doi: 10.1002/chem.200305709.

Abstract

We describe a new strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays. This strategy relies on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides promoted by the Sm-BINOL-Ph(3)As[double bond]O (1:1:1) complex, followed by a conversion of morpholinyl amides into ketones and diastereoselective ketone reduction. Highly enantio- (up to >99 % ee) or diastereoselective (up to >99.5:0.5) epoxidation was achieved using 5-10 mol % of the Sm complex to afford synthetically very useful, nearly optically pure alpha,beta-epoxy morpholinyl amides. Stereoselectivity of the epoxidation was controlled by the chirality of BINOL with overwhelming inherent diastereofacial preference for the substrate. Combination with the syn- and anti-selective ketone reduction with the highly catalyst-controlled epoxidation allowed for an iterative strategy for the syntheses of all possible stereoisomers of 1,3-polyol arrays. Eight possible stereoisomers of 1,3,5,7-tetraol arrays were synthesized with high to excellent stereoselectivity. Moreover, the efficiency of the present strategy was successfully demonstrated by enantioselective syntheses of several 1,3-polyol/alpha-pyrone natural products, for example, cryptocaryolone diacetate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohols / chemical synthesis*
  • Amides* / chemical synthesis
  • Amides* / chemistry
  • Catalysis
  • Epoxy Compounds / chemical synthesis
  • Lanthanum / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Organometallic Compounds / chemistry*
  • Pyrones / chemical synthesis
  • Samarium / chemistry
  • Stereoisomerism

Substances

  • Alcohols
  • Amides
  • Epoxy Compounds
  • Organometallic Compounds
  • Pyrones
  • Samarium
  • Lanthanum