Rhodium-Catalyzed C-H Amination: A Case Study of Selectivity in C-H Functionalization Reactions

An advanced undergraduate organic chemistry laboratory experiment involving a rhodium-catalyzed intermolecular hydrocarbon C-H oxidation reaction is described. In the initial phase of this lab, students conduct a C-H amination reaction of ethylbenzene and isolate a benzylic amine product. In the second part of the lab, competition experiments are performed to compare the relative rates of C-H insertion with electronically disparate para-substituted ethylbenzene derivatives. Reaction progress is monitored by thin-layer chromatography and the outcome quantitatively assessed using ¹H NMR spectroscopy. Data from competition experiments form the basis for a discussion of reaction mechanism including analysis of putative transition structures and relative potential energy barriers for C-H oxidation. Experiments have been designed such that instructors can tailor the level of detail and discussion from introductory to advanced.