6-O-demethylation of the thevinols with lithium aluminium hydride: Selective demethylation of a tertiary alkyl methyl ether in the presence of an aryl methyl ether
Sw. Breeden et al., 6-O-demethylation of the thevinols with lithium aluminium hydride: Selective demethylation of a tertiary alkyl methyl ether in the presence of an aryl methyl ether, HELV CHIM A, 82(11), 1999, pp. 1978-1980
In the pursuit of ring-constrained analogues of buprenorphine, we wished to
prepare 6-O-demethylated analogues of the thevinols and orvinols. Previous
ly it had been disclosed that lithium aluminum hydride (LAH) in THF contain
ing a chlorinated solvent could achieve this transformation. Here we report
the results of our work with LAH in the non-coordinating solvent toluene.
In refluxing toluene, the selective 6-O-demethylation of thevinols could be
achieved with no 3-O-demethylation being observed. It appears that a C(20)
-OH or C(2O)-NH2 group is needed on the substrate for this hydrogenolysis t
o proceed.