Scientific Publications

An oligomer-based approach to skeletal diversity in small-molecule synthesis.

Publication TypeJournal Article
AuthorsSpiegel, DA, Schroeder FC, Duvall JR, and Schreiber SL
AbstractAccess to small molecules of widely varying molecular shapes has been identified as an enabling step in the discovery of biologically active materials. In this communication we introduce an approach to the systematic development of architecturally distinct chemical compounds based upon the assembly of reactive monomers into linear oligomers, each of which encodes a unique molecular framework under a common set of reaction conditions. Certain products of the initial chemical transformation (Ru-catalyzed metathesis reaction) encode additional skeletons upon treatment with a second common set of reagents (Diels-Alder dienophiles). Application of this oligomerization approach has led to the discovery of a previously unreported tandem ene-yne-yne metathesis-6pi-electrocyclization-1,5-hydride migration that converts a linear substrate into a complex tricyclic 1,3-diene in a single step. Thus, the reported strategy might serve not only as a generator of skeletally diverse small molecules but also as a discovery platform for the identification of novel chemical transformations.
Year of Publication2006
JournalJournal of the American Chemical Society
Volume128
Issue46
Pages14766-7
Date Published (YYYY/MM/DD)2006/11/22
ISSN Number0002-7863
DOI10.1021/ja065724a
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/17105261?dopt=Abstract