Cross Metathesis

Cross metathesis (CM) is an attractive alternative to other olefination methods due to the large variety of commercially available olefin starting materials and to the high functional group tolerance of the ruthenium metathesis catalysts. Depending on the types of olefins involved in the metathesis reaction, cross metathesis reactions generally fall into one of three types:

 I. Chain-extending. This brings together two olefins to make a longer chain molecule, an example being the CM of 1-octene with itself to produce 7-octadecene and ethylene gas.

II. Chain-shortening. Functionally the opposite of chain-extending, the most common variant is ethenolysis of an internal olefin to produce terminal olefins. In the example below, methyl oleate is converted to 1-decene and the unsaturated ester.

III. Functionalizing. A terminal olefin can be carried through a synthetic sequence and “functionalized” at a late stage by CM with a functional olefin. An example would be the CM of the terminal olefin below with methyl acrylate to give an unsaturated ester.

Cross metathesis reaction between two different olefins with similar reactivities can yield an equilibrium distribution of metathesis products. In the example below where equivalent ratios of olefin-R₁ and olefin-R₂ are metathesized to yield an equilibrium distribution of 6 metathesis products, 25% each of the homodimers R₁-R₁ and R₂-R₂ and 50% of the crossed product R₁-R₂, and each having cis and trans isomers.

Cross metathesis reactions usually produce trans double bonds, but the selectivity depends on the reaction partners and the metathesis catalyst. Recent reports from Schrock and Hoveyda using conformationally restricted molybdenum complexes highlight their new cis selective catalysts (see J. Am. Chem. Soc., 2009, 131, 7962).

A large number of examples of using cross metathesis in total synthesis have been published. In a recent example, Nicolau’s group used cross metathesis in the total synthesis of an analog of the natural product Biyouyanagin A. A trisubstituted olefin (type III) was reacted with 5eq of 1,4-diacetoxybutene. The final product was produced with remarkable chemo- and stereoselectivity in 73% yield. No products arising from cross metathesis of any of the other double bonds present was observed. (J. Am. Chem. Soc. 2008, 130, 11114). 

Cross metathesis can also be useful to produce highly functionalized reagents for further transformations, for example unsaturated phosphonates, vinyl and allylboronates, vinyl sulfones and vinyl epoxides.

Be Sociable, Share!

•