Enantioselective Synthesis of 3-Alkyl-1,5-Functionalized 1,4-Diynes via Isoxazol-5(4 <i>H</i> )-ones

An enantioselective strategy for the synthesis of chiral 3-alkyl-1,5-functionalized 1,4-diynes is reported. The method involves a highly enantioselective organocatalytic conjugate addition of isoxazol-5(4<i>H</i>)-ones to nitroenynes followed by a Zard-type transformation under one-pot conditions yielding chiral skipped diynes in good overall yields and with excellent enantioselectivities. This study highlights the synthetic versatility of the isoxazol-5(4<i>H</i>)-one scaffold and its value as a platform for accessing structurally diverse and synthetically relevant building blocks.