Convergent solution-phase combinatorial synthesis with multiplication of diversity through rigid biaryl and diarylacetylene couplings

The solution-phase synthesis of iminodiacetic acid diamide libraries Linked to aryl iodides and their Pd-catalyzed dimerization are detailed. Mixtures containing 64 980 components are synthesized in only 4 steps from N-BOC-im inodiacetic acid anhydride (1) and 21 readily available starting materials, demonstrating the multiplication of diversity achievable by the convergent assembly of building blocks. Both biaryl formation and sequential Stille c ouplings with bis(tributylstannyl)acetylene are utilized to dimerize the fu nctionalized iminodiacetic acid diamide precursors resulting in product lib raries with two sets of binding groups separated by variable length rigid l inkers suitable for probing protein-protein interactions. Deconvolution lib raries synthesized alongside the full mixtures allow for identification of active components.