Position of Coordination of the Lithium Ion Determines the Regioselectivity of Demethylations of 3,4-Dimethoxymorphinans with L-Selectride

L-Selectride is an efficient agent for the 3-O-demethylation of opioids and is known to cleave the least hindered methoxyl group in a molecule.
The treatment of a 3,4-dimethoxymorphinan containing a 6-ketal with L-Selectride gave selective 4-O-demethylation, rather than cleavage of
the less hindered 3-methoxyl. In contrast, a 3,4-dimethoxymorphinan lacking a 6-ketal gave selective 3-O-demethylation, suggesting that the
regiochemistry of L-Selectride-mediated O-demethylation can be manipulated through altering the position of coordination of the lithium ion.