Intramolecular hetero-Diels-Alder reactions of imine and iminium dienophiles: quantum mechanical exploration of mechanisms and stereoselectivities

J Org Chem. 2008 Apr 4;73(7):2679-86. doi: 10.1021/jo702576r. Epub 2008 Mar 8.

Abstract

A series of intramolecular hetero-Diels-Alder reactions of iminium and imine dienophiles has been explored with density functional theory using the B3LYP functional and 6-31+G* basis set. Aqueous solvation energies were calculated with the CPCM method. DFT predicts that these reactions are concerted but involve highly asynchronous transition states. Stereochemical preferences of imine cycloaddition transition states arise from electron repulsion of the nitrogen lone pair with electron density from the butadiene moiety. Protonation of the nitrogen leads to a highly asynchronous transition state. The iminium dienophiles are predicted to have a 17 kcal/mol lower barrier than the corresponding imines, even in aqueous solution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkadienes / chemistry*
  • Computer Simulation
  • Cyclization
  • Imines / chemical synthesis*
  • Imines / chemistry*
  • Models, Chemical
  • Molecular Structure
  • Quantum Theory*
  • Stereoisomerism

Substances

  • Alkadienes
  • Imines