Synthesis of Cyclobakuchiols A, B, and C by Using Conformation-Controlled Stereoselective Reactions

Cyclohexanone with the pMeOC6H4 and CH2C(Me) substituents at the C3 and C4‐positions was prepared from (+)‐β‐pinene and converted to the allylic picolinate by a Masamune–Wittig reaction followed by reduction and esterification. Allylic substitution of this picolinate with Me2CuMgBr⋅MgBr2 in the presence of ZnI2 proceeded with γ regio‐ and stereoselectively to afford the quaternary carbon center on the cyclohexane ring with the CH2CH and Me groups in axial and equatorial positions, respectively. This product was converted to cyclobakuchiol A by demethylation and to cyclobakuchiol C by epoxidation of the CH2C(Me) group. For the synthesis of cyclobakuchiol B, the enantiomer of the above cyclohexanone derived from (−)‐β‐pinene was converted to the cyclohexane‐carboxylate, and the derived enolate was subjected to the reaction with CH2CHSOPh followed by sulfoxide elimination to afford the intermediate with the quaternary carbon center with MeOC(O) and CH2CH groups in axial and equatorial positions. The MeOC(O) group was transformed to the Me group to complete the synthesis of cyclobakuchiol B. Control is key! Synthesis of cyclobakuchiols A and C was stereoselectively accomplished by conformation‐controlled substitution of allylic picolinate with Me2CuMgBr⋅MgBr2/ZnI2. On the other hand, cyclobakuchiol B was synthesized by stereoselective addition of the cyclohexanecarboxylate enolate to CH2CHSOPh (see scheme).