Formation of Seven-membered Carbocycles by RCM

RCM of 1,8-dienes constitutes an efficient access to cycloheptenes since di-, tri-, and tetrasubstituted olefins could be elaborated in good yields with catalyst loading as low as 1 mol%. In this context, the highly demanding field of natural product synthesis constitutes an efficient test for the development of more active and 

Trisubstituted olefins embedded in seven-membered carbocycles are also synthesized in high yields from the corresponding 1,8-dienes. In their elegant total synthesis of (—)-cyanthiwigin F (276), Stoltz and Enquist used for the first time catalyst (Ru]-X [49] possessing an increased activity for the generation of trisubstituted olefins. A double Pd-catalyzed decarboxylative allyUc alkylation of 277 in 

309 with great efficiency. This synthetic strategy was later extended to the synthesis of cyanthiwigin W and Z [77]. 

This very efficient RCM should not mask the fact that trisubstituted double bonds of terpenoids, imposed by the biosynthesis pathway from isoprene units, could be challenging to prepare through the RCM of 1,8-dienes as subtle differences in the metathesis precursor can have a dramatic impact on the reaction rate and yields [80]. 

However, during a synthesis of (—)-tormesol (321), a diterpene isolated from Halimium viscosum, the cyclization of the related nonenolizable / -ketoester 322 proved sluggish as only 50% conversion was observed using catalyst [Ru]-I in combination with Ti(Oi-Pr)4 (1 equiv.). The more active [Ru]-II overcame this limitation and allowed the synthesis of cycloheptene 323 in excellent yield with a low 

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