Synfacts 2006(4): 0321-0321  
DOI: 10.1055/s-2006-932069
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart · New York

Predicting Regioselectivity in Cross-Coupling of Polyhaloheteroaromatics

Contributor(s): Victor Snieckus, Oleg M. Demchuk
S. T. Handy*, Y. Zhang
Middle Tennessee State University, Murfreesboro and Binghamton University, USA
Further Information

Publication History

Publication Date:
24 March 2006 (online)

Significance

A simple predictive tool for the re­gioselectivity of the widely used transition-metal-catalyzed cross-coupling reactions of polyhaloheteroaromatics based on 1H NMR spectroscopy of parent heteroaromatic compounds is proposed. An analysis of the extensive literature data of cross-coupling regioselectivity in 5- and 6-membered ring heterocycles and their 1H NMR spectra suggest that the initial site of coupling is always at the more electron-deficient center which correlates with the larger proton chemical shift. Interesting sequential reactions by variations of conditions (e.g., Negishi followed by Kumada-Corriu couplings) were established. Application of this tool to non-heteroaromatic polyhalo systems also led to predictable results.