Sequential ortho-lithiations; the sulfoxide group as a relay to enable meta-substitution.
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.
Flemming
Jonathan P
JP
Chemical Research Laboratory, Mansfield Rd, Oxford, UK OX1 3TA.
Berry
Malcolm B
MB
Brown
John M
JM
D018360:Crystallography, X-Ray; D008094:Lithium / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry; D013454:Sulfoxides / Q000737:chemistry*
D011799:Quinazolines; D013454:Sulfoxides; D008094:Lithium