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

Organic & Biomolecular Chemistry Pub Date: 2008-02-25 DOI: 10.1039/B716954J

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.

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