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

Cyclohexanone with the pMeOC(6)H(4) and CH2C(Me) substituents at the C3 and C4-positions was prepared from (+)--pinene and converted to the allylic picolinate by a Masamune-Wittig reaction followed by reduction and esterification. Allylic substitution of this picolinate with Me2CuMgBrMgBr2 in the presence of ZnI2 proceeded with regio- and stereoselectively to afford the quaternary carbon center on the cyclohexane ring with the CH2CH and Me groups in axial and equatorial positions, respectively. This product was converted to cyclobakuchiolA by demethylation and to cyclobakuchiolC by epoxidation of the CH2C(Me) group. For the synthesis of cyclobakuchiolB, the enantiomer of the above cyclohexanone derived from (-)--pinene was converted to the cyclohexane-carboxylate, and the derived enolate was subjected to the reaction with CH2CHSOPh followed by sulfoxide elimination to afford the intermediate with the quaternary carbon center with MeOC(O) and CH2CH groups in axial and equatorial positions. The MeOC(O) group was transformed to the Me group to complete the synthesis of cyclobakuchiolB.