Iridium-catalyzed C–H borylation of quinolines and unsymmetrical 1,2-disubstituted benzenes: insights into steric and electronic effects on selectivity
2012; Royal Society of Chemistry; Volume: 3; Issue: 12 Linguagem: Inglês
10.1039/c2sc20776a
ISSN2041-6539
AutoresHazmi Tajuddin, Peter Harrisson, Bianca Bitterlich, J.C. Collings, Neil Sim, Andrei S. Batsanov, Man Sing Cheung, Soichiro Kawamorita, Aoife C. Maxwell, Lena Shukla, James Morris, Zhenyang Lin, Todd B. Marder, Patrick G. Steel,
Tópico(s)Catalytic Cross-Coupling Reactions
ResumoBorylation 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.
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