Enantioselective Access to (−)‐ Ambrox ® Starting from β ‐Farnesene

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 .