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

In the pursuit of ring-constrained analogues of buprenorphine, we wished to prepare 6-O-demethylated analogues of the thevinols and orvinols. Previously it had been disclosed that lithium aluminum hydride (LAH) in THF containing 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(20)-NH₂ group is needed on the substrate for this hydrogenolysis to proceed.