Synthesis of the Spiroketal Fragment of (–)‐Ushikulide A

The stereoselective synthesis of the spiroketal fragment of the immunosuppressant (–)-ushikulide A is described. The salient feature of this synthesis is the construction of the spiroketal moiety by hydrolysis of a dialkylated tosylmethyl isocyanide derivative derived from alkylation of tosylmethyl isocyanide (TosMIC) with suitably substituted halohydrin derivatives. The key functionalized tetrahydropyran ring was constructed by using Prins cyclization of the α-acetoxy ether.