3.4- Epoxy-4-methylcyclohexanol

Greg Nard added an equivalent of 3,4-epoxy-4-methylcyclohexanol to an ether solution of methyl magnesium bromide and then added dilute hydrochloric acid. He expected that the product would be a diol. He did not get any of the expected product. What product did he get ... 

Contrary to the case of anionic reactions, the formation of a strong proton-bound dimer for alcohols suggests that nucleophilic displacement may actually involve a frontside attack. Recent experiments carried out at atmospheric pressure by Speranza and Angelini (1980) using radiolytic techniques with isolation and glc analysis of neutral products reveal some interesting stereochemistry. For example, the reaction of protonated epoxy-rra/is-but-2-ene with H20 results in 98% inversion of configuration, while a similar reaction with cis-1 -chloro-4-methylcyclohexane results in approximately 80% of tro/is-4-methylcyclohexanol. With the high pressures utilized and with the possible participation of cluster ions a likelihood in this case, the data are consistent with a Walden inversion for these cases. 

Acid-induced ring opening of 1,2-epoxy-l-methylcydohexarte with HBr. There is a high degree of SN1-llke carbocation character in the transition state, which leads to back-side attack of the nucleophile at the tertiary center and to formation of the isomer of 2-bromo-2-methylcyclohexanol that has -Br and -OH groups trans. 

The mechanisms of these acid-catalyzed epoxide openings are more complex than they at first appear. They seem to be neither purely S l nor Sn2 but instead to be midway between the two extremes and to have characteristics of both. Take the reaction of 1,2-epoxy-l-methylcyclohexane with HBr shown in Figure 18.2, for instance. The reaction yields only a single stereoisomer of 2-bromo-2-methylcyclohexanol in which the -Br and -OH groups are trans, an SN2-like result caused by backside displacement of the epoxide oxygen. But the fact that Br attacks the more hindered tertiary side of the epoxide rather than the less hindered secondary side is an SNl-like result in which the mote stable, tertiary carbocation is involved. 

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