DFT study of the mechanism and origin of enantioselectivity in chiral BINOL-phosphoric acid catalyzed transfer hydrogenation of ketimine and α-imino ester using benzothiazoline

J Org Chem. 2013 Apr 19;78(8):3731-6. doi: 10.1021/jo4002195. Epub 2013 Apr 4.

Abstract

Benzothiazoline is an efficient reducing agent for the chiral BINOL-phosphoric acid catalyzed enantioselective transfer hydrogenation of ketimines and α-imino esters to afford the corresponding amines with high enantioselectivities. DFT studies (M05-2X/6-31G*//ONIOM(B3LYP/6-31G*:HF/3-21G)) revealed the reaction mechanism and the origin of the high enantioselectivity in the present BINOL-phosphoric acid catalyzed transfer hydrogenation of ketimines and α-imino esters using benzothiazoline. The reaction mechanism is similar to that reported in the asymmetric transfer hydrogenation of ketimines using Hantzsch ester. Phosphoric acid simultaneously activates ketimine (α-imino ester) and benzothiazoline to form cyclic transition structures. The high enantioselectivity is attributed to the steric interaction between the substituents at the 3,3'-positions of BINOL-phosphoric acid and substrates. In contrast to the C2-symmetrical Hantzsch ester, the readily tunable 2-aryl substituent of unsymmetrical benzothiazoline plays a significant role in the steric interaction, influencing the asymmetric induction. This feature is responsible for the advantage of benzothiazoline over Hantzsch ester.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzothiazoles / chemistry*
  • Biphenyl Compounds / chemistry*
  • Catalysis
  • Hydrogenation
  • Imines / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Nitriles / chemistry*
  • Oxidation-Reduction
  • Phosphoric Acids / chemistry*
  • Quantum Theory
  • Stereoisomerism

Substances

  • Benzothiazoles
  • Biphenyl Compounds
  • Imines
  • Nitriles
  • Phosphoric Acids
  • ketimine
  • benzothiazoline