Determination of the origin of stereoselectivity in multiple-transition-state reactions using DFT calculations: enantioselective synthesis of homoallylic alcohols from aliphatic methyl ketones via an auxiliary-mediated allylation

J Am Chem Soc. 2008 Apr 2;130(13):4386-95. doi: 10.1021/ja078032a. Epub 2008 Mar 11.

Abstract

Computational investigations on the highly stereoselective allylation of butanone in the presence of a chiral norpseudoephedrine-derived auxiliary have been performed. They suggest an SN1-type mechanism via the attack of allyltrimethylsilane to an intermediately formed oxocarbenium ion. The identification of preferred transition states (TSs) leads to a straightforward rationalization of the observed selectivity which can be extended to analogues of the auxiliary. A screening process has been devised to select 61 potentially relevant TSs from a total of almost 300 theoretically possible TSs. Final results were obtained from gas-phase calculations employing the B3LYP/6-31+G(d) level of theory as well as in dichloromethane solution using the B3LYP/6-311++G(2d,p)//B3LYP/6-31+G(d) level of theory in combination with polarizable continuum model and the UAKS set of radii. The agreement of theoretically predicted and experimentally observed selectivities is very good in both cases. However, the relative energy differences for several relevant TSs differ significantly when going from gas phase to solution, thus illustrating the necessity of performing calculations in solution to draw correct conclusions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Computer Simulation*
  • Ketones / chemistry*
  • Models, Chemical*
  • Molecular Structure
  • Propanols / chemical synthesis*
  • Propanols / chemistry
  • Quantum Theory
  • Reproducibility of Results
  • Stereoisomerism

Substances

  • Ketones
  • Propanols
  • allyl alcohol