Organic Chemistry Portal
Organic Chemistry Highlights

Monday, March 28, 2005
Douglass Taber
University of Delaware

Alkyne Metathesis in Organic Synthesis

While alkyne metathesis is not going to displace alkene metathesis as a synthetic method, it is a complementary approach that can offer advantages.

Catalysts for alkyne metathesis are still under active development. A recent paper by Karol Grela of the Polish Academy of Sciences in Warsaw (J. Org. Chem. 2004, 69, 7748. DOI: 10.1021/jo049158i) provides an detailed overview of the options. The choice is between sensitive preformed catalysts that provide high turnover but require more exacting organometallic techniques, or, alternatively, in situ catalysts that require higher temperature and longer reaction times, but are less expensive and less technically challenging to prepare. For the latter, the inexpensive Mo(CO)6 has been the precursor of choice, with an added phenol ligand. In this paper, Professor Grela and co-workers optimized the supporting phenol, finding that 2-fluorophenol was the most effective. Dimerizations with this catalyst system require no special precautions - indeed, they can be run open to the air. Both cyclodimerization (1->2) and cross metathesis (3->4) proceeded efficiently.

The more widely used alkene metathesis is deficient in that the alkenes so prepared are often mixtures of geometric isomers. Alkyne metathesis offered what promised to be a general solution to this problem. Hydrogenation of the alkyne products to the Z-alkene was straightforward. Reduction of the isolated alkyne to the E-alkene was not so obvious. Alois Fürstner of the Max-Planck-Institut, Mülheim, has surveyed (Tetrahedron 2004, 60, 7315. DOI: 10.1016/j.tet.2004.05.042) several approaches, then optimized the most promising, Ru-mediated hydrosilylation followed by protodesilylation. The procedure worked equally well to construct E,E-dienes. This promises to be a mild and general solution to the long-standing challenge of E-reduction of an alkyne in the presence of other functional groups.

In each of the alkyne metatheses outlined here, the byproduct is the volatile 2-butyne. The alkyne metathesis can only be carried out on internal alkynes, since the metathesis catalysts cyclotrimerize terminal alkynes such as 11 to benzene derivatives. In this context, it may prove useful that readily-available terminal alkynes such as 14 are easily isomerized specifically to methyl alkynes such as 15 (Tetrahedron Lett. 1990, 31, 5843. DOI: 10.1016/S0040-4039(00)97973-5).

D. F. Taber, Org. Chem. Highlights 2005, March 28.