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Synthesis of Cyclobakuchiols A, B, and C by Using Conformation‐Controlled Stereoselective Reactions
Author(s) -
Kawashima Hidehisa,
Kaneko Yuki,
Sakai Masahiro,
Kobayashi Yuichi
Publication year - 2014
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201303538
Subject(s) - cyclohexanone , chemistry , allylic rearrangement , stereoselectivity , cyclohexane , medicinal chemistry , stereochemistry , sulfoxide , carboxylate , quaternary carbon , organic chemistry , enantioselective synthesis , catalysis
Cyclohexanone with the p MeOC 6 H 4 and CH 2 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 Me 2 CuMgBr ⋅ MgBr 2 in the presence of ZnI 2 proceeded with γ regio‐ and stereoselectively to afford the quaternary carbon center on the cyclohexane ring with the CH 2 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 CH 2 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 CH 2 CHSOPh followed by sulfoxide elimination to afford the intermediate with the quaternary carbon center with MeOC(O) and CH 2 CH groups in axial and equatorial positions. The MeOC(O) group was transformed to the Me group to complete the synthesis of cyclobakuchiol B.