Enyne Metathesis

Enyne metathesis is the reaction of an olefin and an alkyne to produce a 1,3-diene.

When an alkyne is available to coordinate a ruthenium alkylidene, the reaction known as enyne metathesis can occur. The mechanism is analogous to an RCM reaction, but due to the added degree of unsaturation, the retro [2+2] reaction forms a new metal alkylidene (IV) that is still attached to the substrate. Enyne metathesis reactions are often run with added ethylene, which will react with the metal alkylidene to give the product shown and turn over the catalyst.

A number of strategies have been developed to leverage the intermediate metal alkylidene intermediate in enyne metathesis reactions. A recent example came out of Daesung Lee’s lab at the University of Illinois, Chicago (Org. Lett. 2009, 11, 2916).  In the context of a formal total synthesis of (–)-cochleamycin A, the Lee group used a silicon tether to template a tandem enyne/RCM sequence.

There are a few slick design elements in this reaction. The temporary silyl tether not only brings the two fragments together, but also enforces exclusive formation of the desired (E,Z)-1,3-diene. Also critical to the success of this reaction is the fact that the catalyst is coaxed to initiate at the desired olefin by making it terminal and the other one internal. If the catalyst initiated at the wrong olefin, they’d end up with the wrong product. Through careful planning, the Lee group took a reaction that could have given a mess and made it practical!

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