A method of synthesizing .alpha.-sulfonamido amide, carboxylic acid or hydroxamic acid derivatives comprising providing a set of polymer-bound reactant(s) (sulfonamide, aldehyde or ketone, isocyanide or acid) to react with three sets of the other three reactants to form an array of polymer-bound .alpha.-sulfonamido amide-type intermediates and use of such intermediates for the preparation of combinatorial libraries.