© 2007 Data Trace Publishing Company CCC 1431-9268 Small-Molecule Inhibitors of Protein

Purpose of the Study To demonstrate the utility of phosphine-catalyzed additions between poly-mer bound allenoates and imines in the synthesis of libraries for biological screening Background In recent years, organocatalysis has emerged as a powerful technology, allowing synthetic chemists to perform various types of reactions. The cata-lytic activity of the process relies on low-molecular-weight organic mole-cules and does not require involvement of transition or main group metals. The organocatalytic method has become a very attractive strategy, particu-larly in the synthesis of molecules to be used in biological assays, as it avoids any metal contamination of the product. In many cases, the methods are robust, less sensitive toward moisture and oxygen, inexpensive, and also less toxic. Furthermore, this strategy is useful because of its operational sim-plicity and applicability in solid-phase synthesis. Among various organic catalysts, nitrogen- and phosphorus-based compounds are widely used, with amine-containing species being more prevalent than their phosphorus coun-terparts. Since the discovery of [3+2] allenoate–acrylate annulation reaction by Lu and coworkers in 1995,1 numerous reports have been published on forma-tion of functionalized carbocycles and heterocycles using phosphines as nucleophilic catalysts.2,3 The Zhang and Fu groups have separately demon-strated enantioselective versions of this reaction.4,5 Several different natural products have also been synthesized by other groups following thes