Phosphine-Catalyzed Diastereoselective Synthesis of β‑Lactones from Disubstituted Ketenes and α‑Chiral Oxyaldehydes

In
this article we describe a catalytic procedure for the diastereoselective
synthesis of β-lactones bearing two stereogenic centers, from
disubstituted ketenes and α-chiral oxyaldehydes. Tri-n-butylphosphine was found to be the optimal catalyst in
terms of effecting both good yield and diastereoselectivity (dr from
3:1 to 32:1 for 8 examples) in β-lactone formation. The major
isomer of the β-lactone products was determined to be the anti-diastereomer, and its formation was rationalized by
a polar Felkin–Anh model. Involvement of phosphonium enolate
intermediates in the reaction mechanism was indicated through reaction
monitoring by 31P NMR spectroscopy. The utility of the
methodology is demonstrated by a short synthesis of a (+)-peloruside
A synthon.