Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling

J Am Chem Soc. 2016 Jun 29;138(25):7939-45. doi: 10.1021/jacs.6b03444. Epub 2016 Jun 15.

Abstract

We report the development of a new class of guanidine-containing peptides as multifunctional ligands for transition-metal catalysis and its application in the remote desymmetrization of diarylmethanes via copper-catalyzed Ullman cross-coupling. Through design of these peptides, high levels of enantioinduction and good isolated yields were achieved in the long-range asymmetric cross-coupling (up to 93:7 er and 76% yield) between aryl bromides and malonates. Our mechanistic studies suggest that distal stereocontrol is achieved through a Cs-bridged interaction between the Lewis-basic C-terminal carboxylate of the peptides with the distal arene of the substrate.

Publication types

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

MeSH terms

  • Bromides / chemistry
  • Catalysis
  • Chemistry, Organic / methods*
  • Copper / chemistry
  • Kinetics
  • Ligands*
  • Magnetic Resonance Spectroscopy
  • Malonates / chemistry
  • Metals / chemistry
  • Methane / chemistry*
  • Molecular Structure
  • Peptides / chemistry*
  • Protein Binding
  • Protein Domains
  • Stereoisomerism

Substances

  • Bromides
  • Ligands
  • Malonates
  • Metals
  • Peptides
  • Copper
  • Methane