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 Me 2 CuMgBr·MgBr 2 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.