Conformational preferences of methacrolein in Diels-Alder and 1,3-dipolar cycloaddition reactions

J Org Chem. 2006 Dec 22;71(26):9831-40. doi: 10.1021/jo062200k.

Abstract

A B3LYP/6-31G* study has been carried out for the reactions of methacrolein with cyclopentadiene, parent nitrone, 1-pyrroline-1-oxide, and (Z)-C,N-diphenylnitrone, in which the coordination of a Lewis acid (borane) and the solvent polarity (dichloromethane) have been taken into account. Calculated activation parameters, regioselectivities (for 1,3-dipolar cycloaddition reactions), and endo/exo stereoselectivities show good agreement with available experimental data. Gas-phase calculations show a varied behavior of the s-cis/s-trans TS stability for noncatalyzed reactions (from the systematic s-cis preference for the cyclopentadiene reaction to the systematic s-trans predilection encountered in the diphenylnitrone cycloaddition). BH3 coordination leads to a preferential stabilization of s-trans TSs in the reactions of cyclopentadiene (exo approach) and diphenylnitrone but a larger stabilization of s-cis structures in the processes involving the parent nitrone or 1-pyrroline-1-oxide. Additionally, a rather systematic preferential stabilization of s-trans structures is induced by solvent polarity in most reactions. As a consequence, an s-trans preference is predicted in solution for both thermal and catalyzed types of reactions in most approaches. Such a conclusion is consistent with some experimental results suggesting a preference for a particular conformation of the methacrolein-Lewis acid complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrolein / analogs & derivatives*
  • Acrolein / chemical synthesis
  • Acrolein / chemistry
  • Aniline Compounds / chemistry
  • Benzylamines / chemistry
  • Boranes / chemistry
  • Computer Simulation*
  • Cyclic N-Oxides / chemistry
  • Cyclization
  • Cyclopentanes / chemistry
  • Methylene Chloride / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Nitrogen Oxides / chemistry
  • Pyrrolidines / chemistry
  • Stereoisomerism

Substances

  • 1-pyrrolidine-1-oxide
  • Aniline Compounds
  • Benzylamines
  • Boranes
  • C,N-diphenylnitrone
  • Cyclic N-Oxides
  • Cyclopentanes
  • Nitrogen Oxides
  • Pyrrolidines
  • nitrones
  • Methylene Chloride
  • Acrolein
  • methacrylaldehyde