Synfacts 2011(4): 0376-0376  
DOI: 10.1055/s-0030-1259673
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart ˙ New York

Combined Ugi-Pictet-Spengler Synthesis of Polycyclic Ketopiperazines

Contributor(s): Victor Snieckus, Toni Rantanen
W. Wang, S. Ollio, E. Herdtweck, A. Dömling*
University of Pittsburgh, Pennsylvania, USA and Technische Universität München, Garching, Germany
Further Information

Publication History

Publication Date:
18 March 2011 (online)

Significance

Reported is the synthesis of ­polycyclic heterocycles via a three-component, two-step reaction, elaborating on a previously published procedure (W. Wang, E. Herdtweck, A. Dömling Chem. Commun. 2010, 46, 770). A mixture of the components, an electron-rich phenethyl isocyanide, aminoacetaldehyde di­methyl acetal, and an oxocarboxylic acid, is stirred in methanol solution to afford the Ugi products in poor to good yields. The next step is a Pictet-Spengler reaction of these with formic acid (more reactive dimethoxyaryl) or with methanesulfonic acid (less reactive monomethoxy or phenyl), which affords fused piperazinones in poor to good yields. Substrate scope is limited to electron-rich aryl components and to the availability of the oxocarboxylic acids.