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