Rhodium(II)-Catalyzed Regioselective Remote C–H Alkylation of Protic Indoles
Lingheng Kong, Han Xi, Haohua Chen, Huaming Sun, Yu Lan, Xingwei Li
Abstract
Control of regioselectivity that defies the intrinsic reactivity of arene C–H bonds remains a formidable challenge. In this work, dimeric Rh(II) complexes have been applied as an efficient catalyst for the regioselective coupling of NH indoles with diazo compounds. Two-substituted indoles mostly reacted with C(6) selectivity. Mechanistic studies revealed that the regioselectivity results from the hydrogen-bonding directing effect, and the C–C bond formation proceeds via the Friedel–Crafts-type attack of indole toward the Rh(II) carbene species. In contrast, the reaction of 4-methoxyindoles occurred exclusively with the complementary C(7) selectivity.
Topics & Concepts
RegioselectivityChemistryRhodiumCarbeneDiazoIndole testCatalysisSelectivityAlkylationMedicinal chemistryReactivity (psychology)Friedel–Crafts reactionCombinatorial chemistryStereochemistryOrganic chemistryMedicinePathologyAlternative medicineCatalytic C–H Functionalization MethodsCyclopropane Reaction MechanismsCatalytic Cross-Coupling Reactions