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.