Stereoselective Synthesis of (-)-Ambrox via Metalloporphyrin-Catalyzed C(sp3)-H Bond Oxidation of Hydrocarbons.

Ambrox is a naturally tricyclic terpenoid furan, which is mainly responsible for the characteristic pleasant odor of ambergris. A concise synthesis of racemic ambrox was accomplished in a ten-step linear sequence starting from commercially available dihydroboronal with an overall yield of 20.7%. The synthetic strategy features a Brønsted acid-mediated biomimetic cyclization of a monocyclic enol acetate and a late-stage C(sp3)-H bond hydroxylation of hydrocarbons catalyzed by an activated (CO)RuII(TPFPP) complex as the key steps. Building upon this approach, an enantioselective route to (-)-ambrox was successfully achieved in 11 linear steps with 14.9% overall yield by utilizing a chiral alcohol as the key intermediate, which could be conveniently prepared from the relatively inexpensive dihydro-β-ionone via Ru-catalyzed enantioselective hydrogenation of β-monocyclofarnesol.