2 PRACTICAL SYNTHESES OF STERICALLY CONGESTED BENZOPHENONES

Two efficient syntheses of the sterically congested tetraortho-substituted benzophenone portion of balanol 1 (a potent PKC inhibitor) in a protected form are described. Ortho lithiation reactions are employed for the preparation of the required 1,2,3-trisubstituted aryl aldehydes (11 and 26) and for their subsequent coupling reactions (with 6 and 23, respectively). The resulting carbinol intermediates [12, 27 and 35 (from cross coupling of 11 and 23)] were then manipulated to the corresponding benzophenonecarboxylic acids 2, 31, and 39, respectively. This chemistry is amenable to large scale synthesis, and multigram quantities of final products have been prepared.