Expedient Approach to α,β‐Unsaturated δ‐Lactones through a Catalytic Asymmetric [2+2] Cycloaddition

The stereoselective synthesis of the cis‐γ,δ‐disubstituted α,β‐unsaturated δ‐lactone fragment of the leustroducsins or phoslactomycins was accomplished. The new synthetic strategy involves a catalytic asymmetric ketene–aldehyde [2+2] cycloaddition leading to the formation of a cis‐disubstituted β‐lactone. Ring extension by enolate condensation and subsequent recyclisation then gave the target δ‐lactone in a straightforward fashion. Coupling studies with cyclohexanone are also reported. The enantioselective synthesis of a δ‐lactone fragment relevant to the phoslactomycin/leustroducsin family of natural products has been accomplished in a straightforward fashion. The new synthetic strategy involves a Nelson's catalytic asymmetric [2+2] cycloaddition between acyl chlorides and aldehydes, followed by ring extension.