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Enzymatic Resolution of O ‐(Methoxymethyl)‐Protected Tropane‐diols
Author(s) -
Affolter Olena,
Baro Angelika,
Laschat Sabine,
Fischer Peter
Publication year - 2007
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200790206
Subject(s) - chemistry , vinyl acetate , diol , tropane , ether , kinetic resolution , vinyl ether , resolution (logic) , organic chemistry , stereochemistry , enantioselective synthesis , catalysis , copolymer , artificial intelligence , computer science , polymer
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.