ortho-Lithiation of p-bromoanisole (p-BrA): Development of an aryl synthon

ORGN 437

D. W. Slocum, donald.slocum@wku.edu, Troy Reece, Christopher B. White, christopher.white@wku.edu, and Paul E. Whitley, paul.whitley@wku.edu. Department of Chemistry, Western Kentucky University, 1906 College Heights Blvd., Bowling Green, KY 42101
With alkyllithium metalating agents, ortho-lithiation of p-BrA cannot be accomplished as halogen/metal exchange is the initial reaction path. With phenyllithium, ortho-lithiation can be achieved, but the generated by-product, benzene, is now considered hazardous. We advocate use of substituted aryllithium intermediates as surrogates for PhLi. Our ability to generate o-lithiodimethylaniline (o-LiDMA) in efficiencies >95% suggested that this reagent might be effective for lithiation of appropriate halogen-containing aryl substrates. This has now been demonstrated by our use of this protocol to afford o-TMS-p-BrA in good yield. This stable substance can be used to prepare a numerous combination of derivatives via the halogen (halogen/lithium exchange, Grignard formation, aryl coupling, etc.) as well as regiospecific introduction of other substituents by use of ipso-displacement of the TMS moiety. A series of o-substituted p-BrA's has been prepared in good yield via the readily prepared o-Li-p-BrA intermediate. These include those from treatment of the intermediate with cyclopentanone, iodine, Eschenmoser's salt, etc. Further amplification of this methodology to other suitable haloaryl sustrates will be discussed.
 

Heterocycles and Aromatics, Molecular Recognition and Self Assembly
8:00 PM-10:00 PM, Tuesday, April 8, 2008 Morial Convention Center -- Hall A, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008