An interesting approach in which asymmetric centers are controlled so as to avoid isomeric materials with opposing antipodes in the synthetic sequence was developed by Glidden-Durkee (SCM Corporation) in the early 1960's. (-)-beta-Pinene of very high optical purity occurs as a major constituent in both gum and sulfate turpentine produced in the eastern United States. Typically, these types of turpentine contain 60-65% alpha-pinene and 20-35% (-)-beta-pinene from which the latter is commercially separated by fractional distillation for use as a raw material in resins and for perfume and flavor materials such as geraniol, linalool, citral, nopol, and a multitude of related aromatics. Hydrogenation of (-)-beta-pinene affords predominantly (-)-cis-pinane with the requisite asymmetry at C-1 required for conversion all the way to (-)-menthol. Pyrolysis of (-)-cis-pinane affords optically active 2,6-dimethtyl-2,7-octadiene which can be converted to (+)citronellol by several routes. One procedure involves protection of the 2,3-double bond by reaction with HCl to form 2-chloro-2,6-dimethyl-7-octene followed by anti-Markownikoff addition of HBr. Solvolysis of the intermediate bromo-chloro compound affords a mixture of alpha- and beta-citronellol (either directly or more usually as the ester). [Only the beta-isomer is desired and so the alpha-double bond is subjected to isomerization to the beta position.] Alternatively, direct treatment of 2,6-dimethyl-2,7-octadiene with organoaluminum compounds such as aluminum triisobutyl (or alkyl boranes) and oxidation-hydrolysis affords (+)-beta-citronallal in high yield. This latter sequence offers considerable advantages over the former, provided appropriate safety precautions are employed. Catalytic oxidation of (+)-citronellol gives (+)-citronellal, in good yield, which is then convertible to (-)-menthol by classical procedures. The degree of optical purity of the final product obtained via this procedure is highly dependent on excluding the small percentage of trans-pinane produced in hydrogenation of (-)-beta-pinene. Pyrolysis of this latter material affords antipodal 2,6-dimenthyl-2,7-octadieiie which when carried through the sequence gives (+)-menthol. While seemingly insignificant because of the small percentage generated, this can play a distinct role in the final optical purity of the menthol produced.

1. Leffingwell, J.C. & R.E. Shackelford, Laevo-Menthol - Syntheses and organoleptic properties, Cosmetics and Perfumery, 89(6), 69-89, 1974

2. Hopp, R., Menthol: its origins, chemistry, physiology and toxicological properties, Rec. Adv. Tobacco Science, Vol. 19, 3-46 (1993).