Breaking the regioselectivity rule for acrylate insertion in the Mizoroki-Heck reaction

Proc Natl Acad Sci U S A. 2011 May 31;108(22):8955-9. doi: 10.1073/pnas.1101497108. Epub 2011 May 11.

Abstract

In modern methods for the preparation of small molecules and polymers, the insertion of substrate carbon-carbon double bonds into metal-carbon bonds is a fundamental step of paramount importance. This issue is illustrated by Mizoroki-Heck coupling as the most prominent example in organic synthesis and also by catalytic insertion polymerization. For unsymmetric substrates H(2)C = CHX the regioselectivity of insertion is decisive for the nature of the product formed. Electron-deficient olefins insert selectively in a 2,1-fashion for electronic reasons. A means for controlling this regioselectivity is lacking to date. In a combined experimental and theoretical study, we now report that, by destabilizing the transition state of 2,1-insertion via steric interactions, the regioselectivity of methyl acrylate insertion into palladium-methyl and phenyl bonds can be inverted entirely to yield the opposite "regioirregular" products in stoichiometric reactions. Insights from these experiments will aid the rational design of complexes which enable a catalytic and regioirregular Mizoroki-Heck reaction of electron-deficient olefins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry
  • Carbon / chemistry
  • Catalysis
  • Chemistry / methods*
  • Electronics
  • Electrons
  • Magnetic Resonance Spectroscopy / methods
  • Metals / chemistry
  • Models, Chemical
  • Molecular Conformation
  • Molecular Structure
  • Palladium / chemistry*
  • Software
  • Stereoisomerism
  • Temperature

Substances

  • Alkenes
  • Metals
  • Palladium
  • Carbon