Enantioselective Synthesis of (−)‐β‐Santalol by a Copper‐Catalyzed Enynol Cyclization–Fragmentation Reaction

Abstract

We report herein the first enantioselective, direct synthesis of the highly prized natural sandalwood odorant ( )-b-santalol (( )-1). The key step in the synthesis is an efficient copper-catalyzed rearrangement of an enynol. The increasing scarcity of East Indian sandalwood oil has motivated research chemists over the last 40 years to develop a synthesis of the most valuable component, ( )-b-santalol ( )-1, which makes up 20–25% of the composition of the oil, or its racemate. Despite extensive efforts, this excellent fragrance ingredient is still not commercially available. Recently, we reported the cost-efficient copper-catalyzed cycloisomerization of 5-en-1-yn-3-ols (cyclopropanation/1,2alkyl shift; Scheme 1, A!E) and related enynol esters.