Authors: Evan R. King, Elisabeth T. Hennessy, and Theodore A. Betley
Journal: Journal of the American Chemical Society
Affiliation: Department of Chemistry and Chemical Biology, Harvard University
Proposed catalytic cycle of C-H amination and olefin aziridination.
Controlled cleavage and functionalization of unactivated C-H bonds has been a research goal of countless organometallic chemists. Recent years have seen some modest breakthroughs in the field. As usual, nature uses metalloenzymes containing cobalt (Co) or iron (Fe) to perform these transformations in a very controlled manner which can not be reproduced in the lab. Some of the best catalysts for C-H bond functionalization utilize rhodium or ruthenium, which are quite expensive. The Betley group has developed a coordinatively unsaturated (bound to less molecules than it would like) Fe complex able to carry out group transfer chemistry reminiscent of certain metalloenzymes such as methane monooxygenase and cytochrome P450
The Betley group chose to base their ligand off of dipyrromethene, which is slightly less than half of the biologically important porphyrin. The simple ligand allows for high yielding syntheses of multiple derivatives with varying electronic and steric properties.
The reaction catalyzed by these metal complexes begins with an alkyl or aryl azide, which loses a molecule of dinitrogen to yield a terminal Fe imido complex. The Betley group characterized this catalytic intermediate by x-ray diffractometry and found that the molecule contained the longest reported Fe-imido bond. Magnetic characterization found that the intermediate has a spin of 2, meaning it has 4 unpaired electrons, which explains the long Fe-N bond distance, as there are no empty metal orbitals to for N to form a bond with. Along with computational studies, this allowed the researchers to conclude that the electronic structure of the complex is that of the high-spin Fe(III) (spin 5/2) antiferromagnetically coupled to a radical (spin 1/2) on the imido, giving the overall spin of 2. This unpaired electron density can be seen in the picture above.
In the presence of molecules containing benzyl C-H’s (toluene for example), this Fe-imido intermediate goes on to abstract a benzyl hydrogen atom, leaving a radical delocalized on the aromatic pi system. This radical then attacks the N in what is known as a radical rebound mechanism, reducing the Fe back to Fe(II) and releasing the newly formed amine.
If there are no benzyl protons available, alkenes, such as styrene, can be added to the reaction mixture to form an aziridine. The reaction probably proceeds in way similar to that of the previously described amination. Radical attack on the double bonds terminal C produces the same delocalized radical, which can then attack the N forming an aziridine.
The researchers attribute the reactivity of this complex to its electronic structure, namely the imido radical, which weakens the Fe-N interaction, thereby increasing reactivity. Future work on this project will include expanding the scope of the reaction, including finding other groups to transfer and more substrates.