Reaching For Meta Substitution

A new mode of C–H activation selectively functionalizes the meta position of aromatic rings, chemists at Scripps Research Institute report (Nature, DOI: 10.1038/nature11158). The strategy could make it easier to bring C–H activation to bear on challenging problems in synthesis, including making drugs with sophisticated substitution patterns. Despite advances in the activation of inert C–H bonds, it’s still tough to selectively transform one C–H bond among many in an aromatic ring. Chemists’ typical solution is a directing group, which tends to form a rigid six- or seven-membered ring transition state with a metal catalyst and produces ortho-substituted products. Meta substitution has remained elusive because it would require a larger ring called a cyclophane in the transition state, which would be strained. Jin-Quan Yu, postdoctoral researchers Dasheng (Jackson) Leow and Gang Li, and graduate student Tian-Sheng (Tyson) Mei realized they could relieve that strain by designing a less-rigid transition state....