An Enantioselective Approach to Pinguisane Sesquiterpenes: Total Synthesis of (-)-Pinguisenol and (-)-Isonaviculol

A short and efficient enantioselective approach to pinguisane-type sesquiterpenes has been developed starting from a Hajos-Parrish-type ketone. This led to the first total syntheses of isonaviculol (10 steps, 6.6 % overall yield) and natural pinguisenol (9 steps, 12 % overall yield). The key reactions were regioselective thioketal protection, stereoselective cyclopropanation using Furukawa's protocol, diastereoselective hydrogenation of an olefin using a Thalesnano H-Cube Pro flow reactor, Li/liquid NH3 mediated cyclopropane reduction, and a PCC-mediated 1,3-oxidative transposition sequence.