Divergent synthesis of 1,3,5-trisubstituted benzenes from 2,3,5-triiodobenzoic acid

Based on our previous explorations of o-diiodoarene/NaH as a novel aryne-generation system, herein we present an efficient route for the divergent synthesis of 1,3,5-trisubstituted benzenes. Since carboxylic acid could be converted into a lot of functional groups, in this protocol, the readily available and inexpensive 2,3,5-triiodobenzoic acid (TIBA) was employed as the starting material for the preparation of diverse aryne precursors. With this aryne-generation toolbox, a series of transformations were achieved between various nucleophiles and these aryne precursors, producing 5-iodo-1,3-disubstituted benzenes as valuable intermediates. The subsequent Ullmann reaction then gave hetero-1,3,5-trisubstituted benzenes.