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Our project involves the design and development of bifunctional catalysts for C-H oxidation and their use in the development of new C-C bond forming reactions. The design involves joining a ruthenium-based hydride abstraction catalyst with a group 13 Lewis acid: the Lewis acid will bind the organic substrate in a way that will allow a ruthenium(0) center to abstract a hydride (H-) from an organic substrate. This will release an oxidized organic fragment that, in principle, can participate in C-C and C-X bond forming reactions. In net, this will enable nucleophillic substitution-type reactions with hydride as a leaving group. In our second year of PRF support, we have realized success with some of the organic reactivity that we proposed to develop and have demonstrated some very interesting new coordination chemistry.

Aim 1: Survey the effects of steric and electronic perturbations in cyclopentadienones used as ligands for ruthenium catalysts for alcohol oxidation. Correlate the electrophilicity of the metal (via C=O and C≡O stretching frequencies) with alcohol oxidation rate and mechanism.

We reported this study at the end of year 1 of PRF sponsorship and have not done additional work in this specific aim.

Aim 2: Use group 13-based (Al, B) Lewis acids to modify cyclopentadienylruthenium catalysts to enable selective C-H bond activation and functionalization in ethereal C-H groups through a bifunctional catalysis strategy.

Our first plan to functionalize the Shvo system (A) resulted in decomposition of the catalytic materials, and we switched to a dipyridylborate ligand complex (C below, year 1). C is prepared through the intermediacy of E, a C-H agostic complex that has structural homology to our proposed transition state for boron-directed C-H cleavage. This year we determined the structure of E and measured the thermochemistry for formation of this agostic bond. Although the agostic interaction is a 5.5 kcal/mol weaker bond than a coordinated acetonitrile, the entropy of driving off the acetonitrile solvent makes it possible to observe both species in acetonitrile solution. Importantly, this is the first case we know in which a C-H bond expels a ligand from a coordinatively saturated, 18-electron metal center (D), a situation that is made possible by the cooperative reactivity of the two sites of the proposed catalyst. This is our first demonstration of synergistic reactivity made possible by bringing boron and ruthenium together in the same complex. Furthermore, this experiment necessitated that we develop a procedure to acquire inversion recovery kinetics data in the new Varian VNMRJ software. This work is currently submitted for publication as an NMR method.

Aim 3: Apply the new hydride abstraction catalyst to C-C bond formation problems that are otherwise unsolved or difficult to achieve (Scheme 1C), specifically synthesis of tertiary ethers, ketone-ketone crossed aldol reactions, and oxidation-initiated epoxide opening cascades.

In this second year of PRF sponsorship, we have identified a number of reactions for which C is a catalyst. Some of these are illustrated below. In addition to these, we have found that this catalyst is reactive in directed H/D exchange, water oxidation, and other reactions of relevance to bulk chemical production.

We have observed alcohol oxidation catalyzed by C, but we have not determined whether this reaction proceeds through a bifunctional catalytic mechanism. We have also shown that C is a catalyst for aerobic C-H cyanation, thus demonstrating an example of our proposed C-H to C-C conversion reactivity. We are investigating the scope and mechanism of this transformation. We have also utilized C in a Conia-type coupling of 1,3-diketones and alkynes. We’ve gone on to optimize this reaction and a report is forthcoming.

In sum, my group has accomplished several of our proposed aims from the original PRF type G proposal and in so doing have opened several new avenues of investigation for our future. We thank the PRF for its sponsorship at this early point in the life of our group.