New applications of the Zincke ring opening of pyridines for complex molecule synthesis

ORGN 222

Christopher D. Vanderwal,, Department of Chemistry, University of California, 1102 Natural Sciences II, Department of Chemistry, Irvine, CA 92697
Zincke discovered the ring opening reaction of pyridinium salts by amine nucleophiles over a century ago, and the product aminopentadienals are now known as Zincke aldehydes. Use of the ring opening reaction, and the highly conjugated products that result, has been minimal and sporadic in the context of complex molecule synthesis. We have discovered a new strategy for heterocycle synthesis based on Zincke ring openings of pyridinium salts that bear tethered amine nucleophiles; its application to a concise synthesis of the anthramycin family of antitumor antibiotics will be discussed. During attempts to synthesize indole alkaloids by Zincke aldehyde cycloaddition reactions, an unusual pericyclic reaction cascade that converts Zincke aldehydes into α,β,γ,δ-unsaturated amides with high Z-selectivity was uncovered. Combination of this rearrangement with a subsequent intramolecular Diels–Alder reaction provides rapid and stereocontrolled access to polycyclic lactams. Finally, an intramolecular formal cycloaddition reaction of Zincke aldehydes with indole dienophiles was developed as the key step in a short synthesis of Strychnos alkaloids.

Young Academic Investigators
8:00 AM-12:00 PM, Monday, August 17, 2009 Walter E. Washington Convention Center -- 207A, Oral

Division of Organic Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009