Total Synthesis
of Tetrahydrolipstatin and Stereoisomers
via a Highly Regio- and Diastereoselective Carbonylation of Epoxyhomoallylic
Alcohols
- Publication date
- Publisher
Abstract
A concise
enantioselective synthesis of tetrahydrolipstatin (THL)
and seven stereoisomers has been achieved. The synthesis of THL was
accomplished in 10 steps and 31% overall yield from an achiral ynone.
Key to the success of the approach is the use of a bimetallic [Lewis
acid]<sup>+</sup>[Co(CO)<sub>4</sub>]<sup>−</sup> catalyst
for a late-stage regioselective carbonylation of an enantiomerically
pure <i>cis</i>-epoxide to a <i>trans</i>-β-lactone.
The success of this route to THL and its stereoisomers also demonstrated
the practicality of the carbonylation catalyst for complex molecule
synthesis as well as its functional group compatibility