57th Annual Report on Research 2012 Under Sponsorship of the ACS Petroleum Research Fund

Activation of unactivated C-H bonds of hydrocarbons is one of fundamental chemical transformations, which could have enormous impact on efficient use of ubiquitous petroleum products if a practical process can be developed. Cyclometalation, an intramolecular version of the C-H bond activation, is an important reaction used to study the mechanism of the C-H bond activation. Selectivity is a fundamental issue in all chemical reactions. Recently, we have discovered a solvent-controlled switch between sp² and sp³ C-H bond activation by platinum (II) in the cycloplatination of 6-(N-alkyl-N-phenylamino)-2,2’-bipyridine, which allows selectively activate either sp² or sp³ C-H bond. In acetic acid the reaction of 6-(N-alkyl-N-phenylamino)-2,2’-bipyridine with K₂PtCl₄ produced predominantly sp³ C-H activation products, however the reaction in acetonitrile gave selectively sp² C-H activation products. Further deuterium labeling experiments suggested that the reaction in acetic acid was thermodynamically controlled while the reaction in acetonitrile was kinetically controlled. In the proposed research, we intended to further explore the control in selective carbon-hydrogen bond activations.

Although the selectivity control was nearly perfect for the reaction of 6-(N-methyl-N-phenylamino)-2,2’-bipyridine, there are some issues with other substrates. Particularly, the reaction of 6-(N-isopropyl-N-phenylamino)-2,2’-bipyridine with K₂PtCl₄ showed poor selectivity (70%) of sp² C-H bond activation in acetonitrile. Furthermore, low yield of sp³ C-H bond activation product was observed in acetic acid. We have proposed that the poor selectivity might be due to the hydrogen chloride released from the sp² C-H activation, which may catalyze the isomerization of sp² C-H bond activation product to thermodynamically more stable product resulted from the sp³ C-H bond activation. Therefore, we have examined the effect of several bases including Na₂CO₃, NaOAc, pyridine, triethylamine, diisopropylethylamine, and tetramethylpiperidine on the selectivity of the sp² C-H bond activation of 6-(N-isopropyl-N-phenylamino)-2,2’-bipyridine in acetonitrile. It was found that the addition of one equivalent of a base improved the selectivity of the sp² C-H bond activation substantially from 70% to 96-100% depending on the bases used. When less hindered bases were used, the reaction was much slower, probably due to the coordination of the base to the platinum, thus lower the reactivity of the platinum complex. The use of bulky bases such as tetramethylpiperidine and diisopropylethylamine turned to be the best of the choices, since they can neutralize the HCl generated from the fast sp² C-H activation but do not coordinate to the platinum strongly. On the other hand, we found that when two equivalents of the 6-(N-isopropyl-N-phenylamino)-2,2’-bipyridine relative to K₂PtCl₄ were used in the reaction, exclusive formation of the sp² C-H bond activation was observed. Obviously, the excess amount of the ligand served as the HCl scavenger.

To further understand this interesting intramolecular C-H bond activation process, a few of other 6-substituted 2,2’-bipyridines were prepared and their reactions with K₂PtCl₄ under different conditions were attempted. It was found that the reactions of 6-(1-phenylvinyl)-2,2’-bipyridine and 6-(prop-1-en-2-yl)-2,2’-bipyridine with K₂PtCl₂ proceeded to produce exclusively the product through the vinylic C-H bond activation, regardless whether in acetonitrile or acetic acid. The reaction of 6-(1-phenylvinyl)-2,2’-bipyridine indicated that the formation of a fused five-five-membered metallacycle was preferred and the reaction of 6-(prop-1-en-2-yl)-2,2’-bipyridine suggested that the sp² C-H bond activation is preferred. Other interesting results were also obtained. For example, the reaction of 6-(3-butenyl)-2,2’-bipyridine with K₂PtCl₄ proceeded with the isomerization of the double bond to form a fused five-five-membered metallacycle. It would be interesting to further investigate the isomerization mechanism and to examine whether the isomerization of the double bond proceeded prior to the C-H bond activation or following the C-Pt bond formation or during the C-H bond activation process. More experimental designs are clearly necessary. One closely related ligand, 6-allyl-2,2’-bipyridine, is the next one to be examined.

Finally, during the course of our study, we have also developed a new synthetic method involving the oxidative addition of heteroaryl halide to Cp₂ZrBu₂ (Negeshi reagent) to form the heteroarylzirconocene halides and their subsequent cross coupling with functional aryl and heteroaryl halides. This method allows us to prepare a variety of ligands for studying the intramolecular organometallic C-H bond activation.

As we are making steady progress on the proposed research, we are also planning DFT theoretical calculations to study the reaction mechanisms through collaboration with one of computational chemists in our department.