Brugia Malayi - Clark Science Center - Smith College

Development of a Tandem Diels-Alder/Pauson-Khand Reaction for the
Synthesis of Tetracycles Mediated by a Cobalt-Complexed Alkyne
Elsa Hinds and Zulema Peralta
The ultimate goal of this project is to cobalt-complex tetraenyne, 12, which will promote a tandem Diels-Alder/Pauson-Khand
reaction to form tetracycle 14. Previous work on this project developed the current synthetic scheme and the plan for this
summer was to continue the scheme in hope of synthesizing acyclic precursor 12. Previous work had successfully synthesized
1-7. Summer work focused on optimizing the Sonogashira reaction (6-7) and Suzuki coupling forming 8. Once 8 was formed, the
synthesis would continue with steps previously completed on a similar acyclic precursor.
Optimization of the Sonogashira reaction on 6 was imperative because previously the largest yield was 50%, which in a 10-
step synthesis is not optimal. To accomplish this, different purification conditions were employed via column chromatography
as well as changing the palladium catalyst from Pd(PPh 3
) 4
to bench-stable Pd(PPh 3
) 2
Cl 2
. Toward the end of the summer the Ph
substrate was changed to a TMS group, and the purification was simple. While the Sonogashira conditions were being optimized,
Suzuki reactions were being performed on pure 7, and the Ph Sonogashira product yielded pure 8 after optimization with base
conditions. Once the pure TMS 7 was available, Suzuki reactions were attempted to no avail. This was likely due to the fact
that TMS alkynes are frequently deprotected in base conditions so a third, alkyl substrate has been tested with success in the
Sonogashira. Once the Sonogashira is optimized, steps toward 12 will continue in the fall. (Supported by the Howard Hughes
Medical Institute and American Chemical Society Fellowship)
Adviser: Kevin Shea
2012
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