Iridium-catalyzed C–H borylation of quinolines and unsymmetrical 1,2-disubstituted benzenes: insights into steric and electronic effects on selectivity?

Chemical Science Pub Date: 2012-09-24 DOI: 10.1039/C2SC20776A

Abstract

Borylation of quinolines provides an attractive method for the late-stage functionalization of this important heterocycle. The regiochemistry of this reaction is dominated by steric factors but, by undertaking reactions at room temperature, an underlying electronic selectivity becomes apparent, as exemplified by the comparative reactions of 7-halo-2-methylquinoline and 2,7-dimethylquinoline which afford variable amounts of the 5- and 4-borylated products. Similar electronic selectivities are observed for nonsymmetrical 1,2-disubstituted benzenes. The site of borylation can be simply estimated by analysis of the 1H NMR spectrum of the starting material with preferential borylation occurring at the site of the most deshielded sterically accessible hydrogen or carbon atom. Such effects can be linked with C–H acidity. Whilst DFT calculations of the pKa for the C–H bond show good correlation with the observed selectivity, small differences suggest that related alternative, but much more computationally demanding values, such as the M–C bond strength, may be better quantitative predictors of selectivity.

Graphical abstract: Iridium-catalyzed C–H borylation of quinolines and unsymmetrical 1,2-disubstituted benzenes: insights into steric and electronic effects on selectivity
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