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Summary: Stereochemical Control of Skeletal
Diversity
Jason K. Sello, Peter R. Andreana, Daesung Lee, and Stuart L. Schreiber*
Department of Chemistry and Chemical Biology, Howard Hughes Medical Institute,
HarVard Institute of Chemistry & Cell Biology, HarVard UniVersity, 12 Oxford Street,
Cambridge, Massachusetts 02138
sls@slsiris.harVard.edu
Received September 13, 2003
ABSTRACT
Substrates having appendages that pre-encode skeletal information (-elements) can be converted into products having distinct skeletons
using a common set of reaction conditions. The sequential use of the Ugi 4CC-IMDA reaction, followed by allylation, hydrolysis, and acylation
of a chiral amino alcohol appendage (-element), leads to substrates for a ROM/RCM or RCM reaction. The stereochemistry of the -element
and not its constitution controls the outcome of the pathway selected. This work illustrates the potential of linking stereochemical control to
the challenging problem of skeletal diversity.
Diversity-oriented synthesis (DOS) aims to yield collections
of products having many distinct molecular skeletons with
controlled variation of stereochemistry in a small number
(between three and five) of steps.1 The primary strategy for
accomplishing skeletal diversity thus far has been to treat a
substrate having potential for diverse reactivity with different
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