Titanium-catalyzed enantioselective synthesis of α-ambrinol

Article abstract of DOI:10.1002/adsc.200700511

We describe the first enantioselective synthesis of the odorant compound (-)-α-ambrinol (96% ee) from commercial geranylacetone. The key steps are a Jacobsen's asymmetric epoxidation and a titanium-catalyzed stereoselective cyclization initiated by radical epoxide opening. The oxirane ring opening proceeds with retention of configuration at the epoxide chiral center, giving a secondary alcohol which can be advantageously exploited to raise the ee provided by the synthetic sequence. We also synthesized (+)-α-ambrinol by a closely related procedure, showing the synthetic versatility of combining titanium-catalyzed cyclization with Jacobsen's epoxidation reactions.