Stereocontrolled synthesis of spiroketals via a remarkable methanol-induced kinetic spirocyclization reaction. Academic Article uri icon

Overview

abstract

  • A methanol-induced kinetic spiroketalization reaction has been developed for the stereocontrolled target- and diversity-oriented synthesis of spiroketals. In contrast to existing methods for spiroketal synthesis, this reaction does not depend on thermodynamic product stability or require axial attack of an oxygen nucleophile. Stereodiverse glycals are alkylated at the C1 position with side chains bearing protected hydroxyl groups. After alcohol deprotection, the glycal is epoxidized stereoselectively, then the side chain hydroxyl is spirocyclized with inversion of configuration at the anomeric carbon by addition of excess MeOH at -63 degrees C. This spirocyclization reaction appears to proceed by MeOH hydrogen-bonding catalysis and has been used to form five- and six-membered rings with stereoisomeric substituents. In some cases, the stereocomplementary spiroketals can be also obtained by classical acid-catalyzed equilibration.

publication date

  • October 12, 2005

Research

keywords

  • Methanol
  • Spiro Compounds

Identity

Scopus Document Identifier

  • 26444612098

Digital Object Identifier (DOI)

  • 10.1021/ja055033z

PubMed ID

  • 16201793

Additional Document Info

volume

  • 127

issue

  • 40