Total Synthesis of Tetrahydrolipstatin and Stereoisomers via a Highly Regio- and Diastereoselective Carbonylation of Epoxyhomoallylic Alcohols

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]⁺[Co­(CO)₄]⁻ 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