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Monday, March 14, 2005
Douglass Taber
University of Delaware

Catalytic C-C Bond-Forming Reactions

Usually, carbon-carbon bonds are formed by coupling two carbons each of which are already functionalized in some way, as with the displacement of a C-Br with NaCN to form C–CN. It would be more efficient, and potentially less expensive and less polluting, if one of the partners could be an ordinary C-H bond. Intramolecular processes for carbene insertion into unactivated C-H bonds have been known for years. Practical intermolecular processes for C-C bond formation to a C-H bond are just starting to appear.

There are two ways to approach this problem. One way is to activate the target C-H with the organometallic catalyst. This process can be remarkably selective. Yasutaka Ishii of Kansai University, Osaka has reported (J. Org. Chem. 2004, 69, 1221. ) that Pd-mediated oxidation of 1, for instance, proceeds predominantly at the para position, leading, after Heck coupling, to the product 2.

The C-H bond does not have to be attached to an aromatic ring. Robert Bergman and Jonathan Ellman of the University of California at Berkeley have reported (Org. Lett. 2004, 6, 1685 . ) that a Rh catalyst will activate 4 to add to simple alkenes such as 3 in a reductive sense, to give 5.

The other way to effect C-H activation is to add a carbene or carbenoid to the C-H bond. One of the most promising ways to generate the required carbene is by catalytic rearrangement of an alkyne. Chuan He of the University of Chicago has observed (J. Org. Chem. 2004, 69, 3669. ) that an Au catalyst will rearrange ethyl propiolate 7 to give an intermediate that inserts into aromatic C-H bonds to give the Z-alkene 8.

Insertion can also be carried out on the C-H bonds of heteroaromatics. Masahiro Murakami of Kyoto University has described (J. Am. Chem. Soc. 2003, 125, 4720. ) a Ru catalyst that will effect rearrangement of a silyl alkyne such as 10 into the vinylidene carbene. The intermediate Ru carbene complex is then electrophilic enough to insert into the aromatic C-H bond. The insertion is highly regioselective. The Au and the Ru alkylidene insertions are geometrically complementary, as Ru gives the E-alkene.

D. F. Taber, Org. Chem. Highlights 2005, March 14.