A formal total synthesis of (±)-α-pinguisene and (±)-pinguisenol

Abstract

Formal total synthesis of (±)-α-pinguisene and (±)-α-pinguisenol, containing a cis-1,2,6,7-tetramethylbicyclo[4.3.0]nonane skeleton incorporating two vicinal quaternary carbon atoms and four cis oriented methyl groups on four contiguous carbon atoms, isolated from liverworts is described. Thus, an orthoester Claisen rearrangement of the allyl alcohol 14, obtained from the Hagemann's ester 15, afforded the ene ester 18. Hydrolysis of the ketal and ester moieties transformed the ene ester 18 into keto acid 23. Intramolecular cyclopropanation of the diazo ketone 24 derived from the keto acid 23 afforded a 3:2 mixture of chromatographically separable tricyclic diones 25 and 26. Simultaneous regioselective reductive cyclopropane-ring cleavage and reduction of the cyclohexanone carbonyl in the dione 25 with lithium in liquid ammonia furnished the keto alcohol 27, which on Wolff-Kishner reduction followed by oxidation of the alcohol afforded the bicyclic ketone 11, Schinzer's precusor of pinguisenol 9 and α-pinguisene 10.