Selective relay alkene metathesis

In the previous section we have demonstrated that alkene RCM is a powerful and broadly applicable method for the synthesis of complex natural products. However, not every diene or polyene substrate can be successfully cyclized even with the significant advantages available by variation of reaction conditimis including catalyst selection, additive use, solvent choice, and concentration, etc. In this regard, selective relay alkene metathesis provides synthetic chemists with an alternative for reviving these otherwise dead systems when such a limitation is encountered. 

The relay strategy has also been applied to selective alkene cross metathesis (CM). Very recently, Kim and coworkers reported the total synthesis of (+)-3-(Z)-isolaureatin (64) via this strategy (Fig. 20) [65]. The crucial cross metathesis of alkene for stereoselective introduction of the (Z)-enyne unit was successfully realized in 76% yield in the presence of Grubbs catalyst (67) using Lee s protocol. The relay precursor, enyne (66), was subjected to the reaction mixture to initiate the desired process. 

In 2009, Lee and coworkers reported the concise total syntheses of epoxyquinoid namral products (+)-asperpentyn (103), (-)-harveynone (104), and (—)-tricholo-menyn A (105) via cascade enyne metathesis and metallotropic [l,3]-shift (Fig. 29) [78]. In order to initiate the cascade effectively, arelay metathesis strategy was also adopted. By treatment of the polyenyne precursor (106) with Grubbs II catalyst, a mixture of epimers (107) and (108) was isolated in 62% yield. This cascade process selectively commenced from the terminal alkene of the allyl ether (106) to form the relay intermediate (109), which then underwent sequential relay metathesis and enyne metathesis to form alkynyl Ru-alkylidene (111). Subsequent facile metallotropic [1,3]-shift took place to provide the conjugated alkyhdene product (112), which would ultimately deliver the final products (107) and (108) through termination at the less hindered carbon. 

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