Enzymatic Resolution of O-(Methoxymethyl)-Protected Tropane-diols

✍ Scribed by Olena Affolter; Angelika Baro; Sabine Laschat; Peter Fischer

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: German
• Weight: 278 KB
• Volume: 90
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200790206

✦ Synopsis

Abstract

A convenient synthetic route to enantiomerically pure tropane‐diol building blocks is described. The reaction sequence started from tropenone derivatives 1, which were dihydroxylated to give 6,7‐dihydroxytropanone derivatives 2. After introduction of the methoxymethyl (MOM) protecting group in diol 2a, a lipase‐mediated resolution of the resulting racemic mono‐MOM ether (±)‐5d with vinyl acetate and vinyl trifluoroacetate gave the acetates (−)‐6d and (−)‐6f, respectively, with 96–99% ee, and MOM ether (+)‐5d with up to 89% ee. Deacetylation of (−)‐6d afforded quantitatively MOM ether (−)‐5d with 99% ee, the absolute configuration of which was assigned via the modified Mosher method to be (R) at C(6). Enzymatic treatment of unprotected diol 2a with vinyl trifluoroacetate or alkoxycarbonylation resulted in the formation of C~s~‐symmetrical products 9 and 12 rather than the desired desymmetrized derivatives.