Total Synthesis of Lingzhiol and its Analogues through the Wittig Reaction of an Oxocyclopentane Carboxylate

The biosynthesis of polycyclic natural product lingzhiol ( 1 ) through an intramolecular Friedel–Crafts alkylation reaction of an aryl‐substituted cyclopentane epoxide ( 22 ) was attempted. The synthesis of this endocyclic epoxide involved the alkylation of cyclopentane carboxylate 14 with alkyl iodide 25 to afford ketoester 26 . Subsequent Wittig olefination led to exocyclic alkene exo ‐ 15 in good yield. Epoxidation, opening of the epoxide to generate allyl alcohol 29 , and a second epoxidation reaction afforded compounds 22 and 31 . However, presumably owing to stereoelectronic effects, the cyclization of these substrates into polycycles 17 and 32 , respectively, was unsuccessful. Nevertheless, the Wittig reaction to afford exo ‐ 15 allowed us to converge with the previously reported route of Qin et al., which featured the cyclization of spiro epoxide 16 . Thus, lingzhiol is now available in only nine steps. Various analogues of lingzhiol were also prepared, including desoxy derivative 37 , quinone 38 , mono‐methoxy‐deoxy derivative 39 , and ketone 40 .