Neo-Menthol

A satisfactory result was obtained with the ligand 4 [43], which was synthesized from neo-menthol and contains an equatorial cyclopentadienyl group. The enantioselectivity of the opening attained synthetically useful levels (97 3) and the isolated yields were reasonable. Complex 5 [44], incorporating a ligand derived from phenylmenthone, also performed well. An enantioselectivity of 96.5 3.5 was observed. Phenylmenthol has already been extensively and successfully used as a chiral auxiliary [45]. 

Since the tosylate of menthol must be in a boat conformation in order for anti-elimination to occur, its rate of product formation must be slower than that of neo-menthol. This is due to the fact that the boat conformation is at an energy maximum, approximately 7-1 kcal/mole less stable than the chair conformation. Because the boat conformation is at an energy maximum, it is really not a conformer at all instead, it can be considered as a transition state between two conformers. As such, its probability of existence at a given time is very low, and it probably occurs at a ratio of 1 to 10,000 when compared to the more stable chair conformation at room temperature. 

Stereochemical aspects have to be taken into account for the synthetic route to (—)-menthol. The core of menthol is a nonplanar cyclohexane ring with a methyl, hydroxyl, and isopropyl substituents. Menthol has three chiral centers and, thus, eight different conformers are possible. These are (+)- and (—)-menthol, (-1-)- and (—)-neo-menthol, (-1-)- and (—)-isomenthol, and (+)- and (—)-neoisomenthol (Figure 6.17.1). Owing to the above-mentioned properties of (—)-menthol, where all substituents are in the equatorial position, this isomer is the by far most desired product. 

Table 7.39 Eletrooxidations of (neo)menthol catalyzed by nitroxyl catalysts... 

Pickayd ai id fAttlebury have isolated from tihti oil an isomei of menthol, which occurs in small quantity, and which thev have named neo-mcnthol. This body is of particular interest in regard to the Stereochemistry of this important body. 

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