In most cases, olefin metathesis works pretty well, but there are a few exceptions to this rule. For example, hindered olefins can be problematic, and if you’re dealing with polyolefinic substrates, things can get pretty ugly. However, a few tricks have been developed to tame some of these recalcitrant substrates. Relay Ring Closing Metathesis (RRCM) is one of them.
The first example of RRCM was reported by Hoye, as a mean to form a cyclic tetrasubtituted olefin using a first generation catalyst.1 The first-generation Grubbs catalyst has limitations in that it is not reactive enough to directly “bite” on a trisubstituted olefin, so the ruthenium cannot be loaded onto the substrate. However, the catalyst can “bite” on a terminal disubstituted olefin and then cyclize onto a trisubstituted olefin. So, by introducing a relay-arm, and providing an easy-to-load-on olefin A, the ruthenium can be delivered to olefin B via RRCM (releasing the substituted cyclopentene), and then cyclize onto olefin C, yielding the desired tetrasubstituted cyclic olefin.
In its earliest natural product synthesis application, RRCM has been used to effect the formation of a 12-membered-ring precursor of Oximidine III.2 All attempts to cyclize the polyene (see below) failed, but appending a relay-arm on the olefin flanking the epoxide allowed the reaction to proceed without problems.
In the previous cases, the relay strategy helped circumvent the lack of reactivity of hindered olefins, but it can also be useful in differentiating between olefins and competitive metathesis pathways. For example, reacting the triene shown below with a metathesis catalyst results in the formation of both 5- and 6-membered rings. However, if a relay-arm is judiciously introduced, the dihydrofuran is obtained as the sole product.3
These are only a few examples of RRCM, and if you want to know more, I recommend Chapter 9 of “Metathesis in Natural Product Synthesis” as a starting point.
1 Hoye, T. R.; Jeffrey, C. S.; Tennakoon, M. A. Wang, J.; Zhao, H. J. Am. Chem. Soc. 2004, 126, 10210 – 10211.
2 Wang, X.; Bowman, E. J.; Bowman, B. J.; Porco, J. A. Angew. Chem. Int. Ed. 2004, 43, 3601 – 3605.
3 Crimmins, M. T.; Zhang, Y.; Diaz, F. A. Org. Lett. 2006, 8, 2369 – 2372.