Sequential ortho-lithiations; the sulfoxide group as a relay to enable meta-substitution

Org Biomol Chem. 2008 Apr 7;6(7):1215-21. doi: 10.1039/b716954j. Epub 2008 Feb 25.

Abstract

Sulfoxides are known to be powerful directing groups for ortho-lithiation, even in competition with other directors. This has been utilised to introduce substituents meta- to a methoxy-group by sequential lithiation, reaction with Me tert-butylsulfinate, and a second lithiation. Electrophilic trapping of the ensuing lithio-compound with a range of electrophiles followed by reductive removal of the sulfoxide led to meta-substituted anisoles. Some interesting side-reactions were uncovered, including a short synthesis of quinazolines arising from the use of PhCN in the second step.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Lithium / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry
  • Sulfoxides / chemistry*

Substances

  • Quinazolines
  • Sulfoxides
  • Lithium