Iron-Catalyzed C-H Amination

“Iron-Catalyzed Intramolecular Allylic C-H Amination” Paradine, S. M.; White, M. C. J. Am. Chem. Soc. 2012, 134, 2036-2039. DOI: 10.1021/ja211600g

In their recent communication, Christina White’s group at Illinois reports a new allylic C-H amination catalyzed by iron. This builds on previous work from their group in Pd sulfoxide catalyzed allylic amination and iron catalyzed C-H oxidation. In addition to showcasing an exciting reaction, this paper is a great contribution from a green chemistry perspective: they use a cheap, non-toxic metal catalyst to do a highly selective C-H oxidation reaction, one that streamlines the synthesis of C-N bonds directly from the (relatively) unreactive C-H bond. Interestingly, quantitative comparisons are made throughout the paper to the more commonly used Rh2(OAc)4 catalyst.

They start by screening Fe catalysts for intramolecular allylic amination reactivity of sulfamate substrates. Although the polypyridyl Fe complex they have used previously for hydroxylation and desaturation chemistry gave a low yield of product, the phthalocyanine Fe complex 1 gave a good yield (and better than a tetraphenylporphyrin iron complex) of allylic amination. Importantly, they obtained only trace quantities of the aziridination product, showing the high selectivity of the iron-catalyzed reaction (>20:1).

Using the optimized conditions, they then report an impressive olefin substrate scope, including styrenyl, trisubstituted, terminal, and cyclic olefins. Their conditions also successfully functionalize benzylic and tertiary C-H bonds, the latter with complete retention of configuration. Note that mechanistically this latter finding implies a very fast rebound step following the tertiary H-atom abstraction by a proposed metal nitrenoid intermediate.

With such a large substrate scope, the authors were able to investigate the ability of their catalyst to distinguish between multiple C-H bonds in a single substrate, either electronically or sterically. For example, they found that allylic amination is preferred over benzylic, ethereal, tertiary, and secondary C-H amination, in line with the bond dissociation energies of the C-H bonds. It is noteworthy that their catalyst exhibited higher selectivities than the usual workhorse for C-H amination, Rh2(OAc)4.

Lastly, in light of the retention of configuration finding (see above), they investigated the mechanism by measuring a kinetic isotope effect (2.5 vs 1.8 for Rh2(OAc)4) and by using an olefinic substrate capable of E/Z isomerization. Both experiments were consistent with a rate-determining H-atom abstraction to generate a short lived carbon radical intermediate. Note that the Rh2(OAc)4-catalyzed reaction with the Z substrate proceeded with no isomerization, suggesting a distinct mechanism for the Rh-catalyzed reaction.

Overall, this paper highlights a great reaction that complements the wealth of C-H amination work conducted with Rh catalysts. Importantly, their use of an iron catalyst reveals how earth abundant metal catalysts can compete with the tried and true – but rare, expensive and potentially harmful – Pt group metals.

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2 Responses

  1. Do you know if this type of reaction works on C-H bonds that are further away from the directing group? Or is it only good for allyl amination beta to the alcohol?

  2. Thanks Courtney!

    As far as I can tell, the communication doesn’t report reactions of any substrates with gamma-allylic C-H bonds so I’m not sure. It’s interesting that the 7-membered ring resulting from such an oxidation is similar to the ring formed from aziridination, which they see very little of in this chemistry.

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