Reports: G1
47987-G1 A Heterobimetallic Catalyst for C-C Bond Formation from C-H Precursors
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 first year of PRF support, we have made significant progress toward the aims stated in our original proposal, which is summarized below.
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 have recently reported the outcome of this study. Although the mechanism of alcohol oxidation with the Shvo catalyst has been established, we have added quantitative understanding to some features of this mechanism that are not well understood. For example, we find that an oxidant as weak as acetone can be used to re-oxidize the intermediate ruthenium hydride without catalyst re-oxidation becoming rate limiting. Furthermore, C-H cleavage is a significantly electrophilic event, as demonstrated by a Hammett reaction parameter of rho = -0.89. We then applied our mechanistic insights to extended the ligand-directed hydride abstraction strategy to include a rare example of an iron(0) oxidation catalyst. In this system we find that the iron homolog of Shvo's catalyst is a moderately reactive catalyst for transfer dehydrogenation of aryl carbinols, but participates in their oxidation without degrading significantly. We have found that this reaction appears to have homology to the Shvo mechanism.
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 expand the Shvo mechanism to a general hydride abstraction catalyst was to functionalize Shvo's catalyst with a boron Lewis acid to enable selective targeting of ethereal C-H groups. Our first experiment involved hydroborating Shvo's catalyst with pinacol borane. We found that we are able to form monomeric complex -A- cleanly in benzene at ca. 30% conversion. Treatment of the resulting solution with α-phenethyl alcohol and benzoquinone resulted in low-conversion of the alcohol to acetophenone and decomposition of the catalytic materials. One possible explanation involves dissociation of the cyclopentadienone-borane B-O bond. We thus re-designed our system around a dipyridylborate ligand complex, pictured below (-B-). -B- is prepared through the intermediacy of -C-, a C-H agostic complex that has structural homology to our proposed transition state for boron-directed C-H cleavage (-D-). We are currently working to optimize complex -B- for C-H activation reactivity.
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.
Toward this end, we have found that our catalyst B is effective in the transfer dehydrogenation of alcohols, Conia-type coupling of 1,3-diketones and alkynes, and aerobic C-H cyanation of N-alkylanilines. The latter is an example of the type of C-H to C-C conversion reaction that we proposed to realize.
In our second year of PRF sponsorship we will continue to build on our success in the first two aims of our proposal by optimizing the oxidation reactivity of catalyst -B- and its relatives. Key problems we will address include the development of reactivity similar to the transformations listed in our stated aim and validation of our proposed bifunctional mechanism.
