J Am Chem Soc. 2006 Sep 06;128(35):11350-1. doi: 10.1021/ja063511f.

Unexpected intermolecular pd-catalyzed cross-coupling reaction employing heteroaromatic carboxylic acids as coupling partners.

Journal of the American Chemical Society

Pat Forgione, Marie-Christine Brochu, Miguel St-Onge, Kris H Thesen, Murray D Bailey, François Bilodeau

PMID: 16939247 DOI: 10.1021/ja063511f

Abstract

Aryl-substituted five-membered heteroaromatics have attracted great interest over the past years due to their presence in a large number of pharmaceuticals and natural products. Recently, an advance in the preparation of these scaffolds was achieved by employing a C-H functionalization strategy. This method allows easy access to these biaryl motifs by precluding the necessity of preparing specific coupling partners, although poor regioselectivity is sometimes observed when more than one reactive C-H is present on the substrate. In an effort to circumvent this liability, we envisioned the use of a carboxylic acid moiety as a blocking group that could be later functionalized or removed. Remarkably, the coupling was found to occur exclusively at the position previously occupied by the acid, even in the presence of a reactive C-H group. This selective transformation was also found to proceed with other heteroaromatic carboxylic acids, allowing for the preparation of a variety of aryl-substituted heteroaromatics that would be difficult to obtain via other methods.

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