Solution-phase combinatorial synthesis: Convergent multiplication of diversity via the olefin metathesis reaction

The solution-phase synthesis of iminodiacetic acid diamides functionalized with omega-alkenes and their dimerization via the olefin metathesis reaction in the preparation of mixture libraries are detailed. Libraries containing as many as 113,232 compounds prepared from only N-BOC-iminodiacetic acid anhydride (1), 15 amines, and 4 omega-alkene carboxylic acids illustrate the diversity that may be achieved by a convergent versus divergent combination of a small number of monomer building blocks that provides the multiplication of diversity typically associated with linear library syntheses including peptides, oligonucleotides and sequential template functionalizations. Unlike the divergent synthesis of such libraries which is amenable to solid-phase synthesis techniques, the convergent synthesis is especially well suited for solution-phase synthesis and is precluded by solid-phase techniques since the combining components typically would be on mutually exclusive phases. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.