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Enantioselective Access to (−)‐ Ambrox ® Starting from β ‐Farnesene
Author(s) -
Chapuis Christian
Publication year - 2014
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.201300286
Subject(s) - chemistry , enantioselective synthesis , isomerization , nitrile , ketone , aldehyde , catalysis , enol , enamine , yield (engineering) , bicyclic molecule , hydrolysis , stereochemistry , organic chemistry , medicinal chemistry , materials science , metallurgy
Starting from inexpensive ( E )‐ β ‐farnesene ( 1 ), an eight‐step enantioselective synthesis of the olfactively precious Ambrox ® ((−)‐ 2a ) has been performed. The crucial step is the catalytic asymmetric isomerization of (2 E ,6 E )‐ N , N ‐diethylfarnesylamine ( 3 ) to the corresponding enamine (−)‐( R , E )‐ 4a , applying Takasago 's well‐known industrial methodology. The resulting dihydrofarnesal ((+)‐( R )‐ 5 ) (90% yield, 96% ee), obtained after in situ hydrolysis (AcOH, H 2 O), was then cyclized under catalytic SnCl 4 conditions, via its corresponding unreported enol acetate (−)‐( R )‐ 4b , to afford trans ‐decalenic aldehyde (+)‐ 6a . Subsequent transformations furnished bicyclic ketone (−)‐ 8a and unsaturated nitrile (+)‐ 11 , both reported as intermediates to access to (−)‐ 2a .