Advances in multi-component reactions for combinatorial chemistry: The “wet” Ugi and Passerini reactions

ORGN 555

Michael C. Pirrung and Koushik Das Sarma. Department of Chemistry, Duke University, B120 Levine Science Research Center, Durham, NC 27708-0317

Multi-component reactions can be significantly accelerated, up to 300-fold compared to reactions in organic solvent, by conducting them in water. This rate acceleration permits building blocks that usually react poorly, such as sterically hindered compounds, to participate in efficient Ugi and Passerini reactions. These reaction conditions uniquely permit the production of b-lactams from b-keto acids, isonitriles, and amines. The rate acceleration is related to the high cohesive energy density of water, which can be further increased by ionic and non-ionic solutes. Reactions in water provide an alternative to high-pressure reactions that is much more practical; the rate accelerations observed suggest that multi-component reactions have negative activation volumes. The reaction products are often insoluble in water, permitting ready purification by filtration to provide unpurified material of adequate purity for initial biological testing.

Combinatorial, parallel, and solid-phase chemistry 1:00 PM-5:00 PM, Wednesday, March 31, 2004 Anaheim Convention Center -- 303A, Oral Division of Organic Chemistry The 227th ACS National Meeting, Anaheim, CA, March 28-April 1, 2004