Efficient Synthesis of Anastrephin via the Allylic Substitution for Quaternary Carbon Construction

Lactone-moiety-attached 2-cyclohexylideneethyl picolinate was prepared through the OH-directed epoxidation (98% ds) of (R)-3-methylcyclohex-2-en-1-ol (99% ee), Horner-Wadsworth-Emmons olefination, conversion to the allylic moiety, and epoxide ring opening with Et(2)AlCH(2)CO(2)t-Bu. The allylic substitution of the picolinate with Me2CuMgBrMgBr2 furnished a quaternary carbon center with 92% ds. Finally, the lactonization of the product, the tert-butyl ester of the seco acid, under acidic conditions, afforded (-)-anastrephin.