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

✍ Scribed by Simon W. Breeden; Andrew Coop; Stephen M. Husbands; John W. Lewis

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: German
• Weight: 59 KB
• Volume: 82
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/(sici)1522-2675(19991110)82:11<1978::aid-hlca1978>3.0.co;2-q

✦ Synopsis

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)ÀOH or C(20)ÀNH 2 group is needed on the substrate for this hydrogenolysis to proceed.