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

Abstract

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.

Catalytic Nitrene Transfer by an FeIV‐Imido Complex Generated by a Comproportionation Process

“…We thus performed competition experiments opposing styrene to p-X-styrenes (X=NO 2 , CN, CF 3 , Cl, Me) and plotted all data in the form of log(Yield X /Yield H ) vs. σ + a parameter adding resonance to dominant inductive effect. [12,46] Combined data of both catalysts (Figure 1, Table 1 and Table S2) gave an excellent correlation (R 2 = 0.98) with a slope value 1 + = À 0.42 in agreement with an electrophilic active species as found for several iron aziridination catalysts. [12,33,34,[47][48][49][50] This observation thus confirms that the same active species is operative whatever 1…”

A broadly applicable quantitative relative reactivity model for nucleophilic aromatic substitution (SNAr) using simple descriptors

“…To complement the existing S N Ar rate data from the literature, we measured relative reaction rates for 74 individual electrophilesincluding many nitrogen heterocycles relevant to pharmaceutical synthesisusing a competition experiment approach, which is commonly used to generate univariate Hammett plots. [76][77][78][79][80][81] Having control over the composition of our training set gives us the exibility to have a varied and balanced distribution of structural features, which is necessary to ensure both accuracy and applicability in making new predictions. To make the model easy to implement, and to reduce the computational cost required, we combined simple and easy-to-obtain ground state molecular descriptors with our own experimentally determined S N Ar rates.…”

Development of Nonclassical Photoprecursors for Rh2 Nitrenes

“…Complexation of these sulfilimine ligands with Rh 2 esp 2 was pursued because (1) Rh 2 esp 2 is commonly employed as a catalyst in nitrene transfer chemistry ,,,,,,,,,, and (2) our previous in crystallo studies employed this complex. , Treatment of Rh 2 esp 2 with 2 equiv of sulfilimine ligands 6a – 6d resulted in the formation of 2:1 complexes 9a – 9d , which feature a N -coordinated sulfilimine ligand on both axial sites of the Rh 2 core (Figure ). In contrast, 6e forms an S -coordinated 2:1 complex with the Rh 2 (II,II) core ( 9e ).…”

“…31−33 Photochemically promoted dibenzothiophene extrusion from 9d would result in an N-arylsulfonyl nitrene featuring pendant methine C−H bonds, which represent potential sites for intramolecular C−H amination. 35 Complexation of these sulfilimine ligands with Rh 2 esp 2 was pursued because (1) Rh 2 esp 2 is commonly employed as a catalyst in nitrene transfer chemistry 1,2,5,7,8,13,14,16,17,36,37 and (2) our previous in crystallo studies employed this complex. 18 ,21 Treatment of Rh 2 esp 2 with 2 equiv of sulfilimine ligands 6a−6d resulted in the formation of 2:1 complexes 9a−9d, which feature a N-coordinated sulfilimine ligand on both axial sites of the Rh 2 core (Figure 2).…”