Thiocarbonyl-enabled ferrocene C–H nitrogenation by cobalt(III) catalysis: thermal and mechanochemical

Versatile C–H amidations of synthetically useful ferrocenes were accomplished by weakly-coordinating thiocarbonyl-assisted cobalt catalysis. Thus, carboxylates enabled ferrocene C–H nitrogenations with dioxazolones, featuring ample substrate scope and robust functional group tolerance. Mechanistic studies provided strong support for a facile organometallic C–H activation manifold.


Results and Discussion
We initiated our studies by probing various reaction conditions for the envisioned C-H amidation of ferrocene 1a (Table 1). Among a variety of ligands, N-heterocyclic carbenes and phosphines provided unsatisfactory results ( far to deliver the desired product, under otherwise identical reaction conditions. With the optimized reaction conditions in hand, we explored the robustness of the cobalt-catalyzed ferrocene C-H amidation with a variety of 1,4,2-dioxazol-5-ones 2 (Scheme 1). Hence, the chemoselectivity of the cobalt catalyst was reflected by fully tolerating sensitive electrophilic functional groups, including amido, chloro, bromo and nitro substituents in the para-, metaand even the more congested ortho-position.
Moreover, differently substituted thiocarbonyls 1 were found to be amenable within the cobalt-catalyzed C-H amidation manifold by weak-coordination (Scheme 3).
Given the versatility of the cobalt-catalyzed C-H nitrogenation, we became intrigued to delineating its mode of action. To this end, C-H amidations in the presence of isotopically labelled co-solvents led to a significant H/D scrambling in proximity to the thiocarbonyl group. These findings are indicative of a reversible, thus facile organometallic C-H cobaltation regime (Scheme 4).
Next, intermolecular competition experiments revealed that electron-rich arylated thiocarbonylferrocene 1 reacted preferen-tially, which can be rationalized with a base-assisted internal electrophilic substitution (BIES) [24,105] C-H cobaltation mechanism. In addition, the electron-rich amidating reagent 2c was found to be inherently more reactive (Scheme 5).
As to further late-stage manipulation of the thus-obtained products, the amidated thiocarbonylferrocene 3aa could be easily transformed into the corresponding synthetically useful aminoketone 4aa (Scheme 6), illustrating the unique synthetic utility of our strategy.
Mechanochemical molecular synthesis has attracted recent renewed attention as an attractive alternative for facilitating sustainable organic syntheses [106]. Thus, we were delighted to observe that the mechanochemical C-H nitrogenations proved likewise viable by thiocarbonyl assistance in an effective manner (Scheme 7).

Conclusion
In conclusion, we have reported on the unprecedented cobaltcatalyzed C-H nitrogenation of ferrocenes by weakly-coordinating thiocarbonyls. The carboxylate-assisted cobalt catalysis was characterized by high functional group tolerance and ample substrate scope. Mechanistic studies provided evidence for a facile C-H activation. The C-H amidation was achieved in a thermal fashion as well as by means of mechanochemistry, providing access to synthetically meaningful aminoketones.