Total Synthesis of Both Enantiomers of Copalol via Optical Resolution of a General Synthetic Intermediate for Drimane Sesquiterpenes and Labdane Diterpenes

The total synthesis of both enantiomers of copalol (6) was accomplished via the optical resolution of a racemic diol [(±)-4] which is a general synthetic intermediate for drimane sesquiterpenes and labdane diterpenes. Esterification between (±)-4 and Boc-l-proline gave the diastereomeric pair of monoesters (5a and 5b) which could be readily separated by flash column chromatography. PDC-oxidation of the resolved 5a and 5b, and subsequent β-elimination gave optically active enones (9 and ent-9). Both enones were respectively converted into (+)-6 in 36% yield and (−)-6 in 26% yield in five steps: (1) Sakurai reaction (TiCl4-promoted conjugate addition of allylsilane), (2) Wittig methylenation, (3) Wacker oxidation, (4) Horner–Emmons reaction, and (5) DIBAL-H reduction.