Domino metathesis reactions enyne

We have found that a combination of intermolecular and intramolecular domino enyne metathesis reactions is also feasible [122]. Reaction between 1,6-heptadiynes 69-72 and allyltrimethylsilane promoted by 2 gave triene cycloadducts 73-76 in moderate-to-good yields (Scheme 22). 

Royer, F., Viiain, C., Eikaiem, L., Grimaud, L. Seiective Domino Ring-Ciosing Metathesis-Cross-Metathesis Reactions between Enynes and Eiectron-Deficient Aikenes. Org. Lett. 2003, 5, 2007-2009. 

A tandem (domino) cross-metathesis reaction between an enyne and 3 equivalents of a conjugated alkene proceeds in dichloromethane at 40 °C for 12 h with a high yield in the presence of the same ruthenium-carbene flve-membered ring compound 8.53, as shown in Eq. (8.21) [54, 55]. 

The last example in this sectimi is the application of a domino intramolecular enyne metathesis/cross metathesis reaction to the total synthesis of (+)-8-epi-xanthatin (133), which was reported by Martin and coworkers [84, 85]. In this study, the metathesis reactions are highly regioselective and leave the exomethylene moiety on the y-lactone intact (Fig. 35). 

Royer F, Vilain C, EUcaiem L, Grimaud L. Selective domino ring-closing metathesis-cross-metathesis reactions between enynes and electron-deficient alkenes. Org. Lett. 2003 5 2007-2009. 

Coupling an ROM event with enyne metathesis opens up further possibilities for RRM. As already discussed for reactions involving only olefins, norbomenes are valuable strained cycloolefins for the ring-opening step [22], Treatment of the norbomene derivative 123 with the first-generation Grubbs catalyst 1 under ethylene atmosphere induced a smooth domino ROM/enyne RCM/diene RCM process with quantitative formation of the tricyclic compound 124 (Scheme 2.45) [22b]. 

Enyne metathesis/metallotropic [l,3]-shift domino processes are also valuable for natural product synthesis [33c,d]. Reaction of substrate 168 with cis-l,4-diacetoxy-2-butene in the presence of Grubbs catalyst 2 generated the intermediate ruthenium alkinyl carbene through a relay RCM with the hberation of 2,5-dihydrofuran followed by metallotropic [l,3]-shift and terminating (Z)-selective CM with the co-olefin to yield the conjugated enediyne 169 (Scheme 2.58) [33c]. The antitumor active Panax ginseng constituent (3R,9R,10R)-panaxytriol was readily synthesized from 169 in six steps. 

The 1,3-dienes resulting from an enyne metathesis can often be coupled with Diels-Alder reactions in a domino transformation. Heating of benzyldimethylsi-lylacetylene with the styrenes 170 and N-phenylmaleimide in the presence of the... 

Enyne metathesis can also be combined with an intramolecular Diels-Alder reaction (IMDA) in a domino manner [35]. Reaction of the dienes 172 with the terminal alkynes 173 in the presence of the phosphine-free catalyst 4 at reflux temperature yielded the carbobicyclic products 174 preferentially via an exo-(E)-anti or endo-(2)-anti transition state for the [4- -2]-cycloaddition step, respectively (Scheme 2.60) [35a[. 

---