Investigation of mixed-valent ruthenium dimers as inner-sphere ketone transfer hydrogenation catalysts

Includes bibliographical references (pages 128-130)Over the last decade and half, a considerable amount of research has been devoted to the development of homogeneous transfer hydrogenation catalysts that transfer hydrogen from inexpensive alcohol solvents to ketone substrates. Most of this work has been based on the groundbreaking Noyori system that exhibits high enantioselectivity toward a limited number of substrates. Despite significant effort, direct connections between ligand design and selectivity remain elusive for Noyori catalysts due to what is now recognized as an outer-sphere mechanism that relies on non-covalent and unpredictable catalyst-substrate interactions. \ud \ud The Kelson group is addressing the vulnerabilities of the Noyori system through the development of inner-sphere transfer hydrogenation catalysts that covalently bind substrates. Specifically, the compounds (Tpy)Ru(Pyo)2(OH2) (Complex 1) and (Tpy)Ru(Pyr)2(OH2) (Complex 2) where Tpy = 2,2':6',2"-terpyridine, Pyo = 2-pyridonate, and Pyr = 2-pyrolidinonate are active ketone transfer hydrogenation catalysts. Surprisingly, these complexes were demonstrated by ESI-MS to function exclusively through dimeric intermediates such as (Tpy)(Pyo)RuII(??-Pyo)2RuIII(Pyo)(Tpy)+ (from Complex 1). The necessary self-assembly of these dimers proved to be a design problem, so the Kelson group investigated the synthesis and catalytic activity of complexes with bisterpyridine binucleating ligands. These efforts are described in this thesis. \ud \ud Binucleating back-to-back bisterpyridine ligands were prepared thorough single-flask polypyridine coupling protocols developed within the Kelson group. The TpyTpy ligand (consisting of two 2,2':6',2"-terpyridine groups directly linked through their 4'-positions) was prepared by the borylation of 4'-chloro-2,2':6',2"-terpyridine followed by Suzuki-Muriaura coupling to another equivalent of the same terpyridine. The TpyPhTpy ligand (where the 4'-positions of two Tpy groups are para-linked through a phenyl ring) were prepared by the single flask diborylation of 1,4-dibromobenzene and subsequent Suzuki-Muriaura coupling to two equivalents of 4'-chloro-2,2':6',2"-terpyridine. These procedures have promise in producing a wider array of ligands when needed. \ud \ud A series of in-situ catalytic tests were used to demonstrate activity among ruthenium complexes with the binucleating bisterpyridine ligands TpyTpy and TpyPhTpy and identify the best ligand sets for closer investigation. These experiments confirmed that bisterpyridyl ruthenium dimers can catalyze ketone transfer hydrogenation and identified [(Tpy)Ru(L3L3)Ru(Pyo)2(OH2)]2+ and [(Bpy)(Cl)Ru(L3L3)Ru(Pyo)2(OH2)]+ (where L3L3 = TpyTpy or TpyPhTpy) as the more promising catalytic structures. \ud \ud A synthetic sequence was developed to directly prepare the [(Tpy)Ru(TpyPhTpy)-Ru(Pyo)2(OH2)](ClO4)2 and [(Bpy)(Cl)Ru(TpyPhTpy)Ru(Pyo)2(OH2)](ClO4) complexes. All products were characterized by ESI-MS and 1H NMR (though the former was far more informative). While the reactions leading to [(Tpy)Ru(TpyPhTpy)Ru(Pyo)2(OH2)](ClO4) presented few problems, those to [(Bpy)(Cl)Ru(TpyPhTpy)Ru(Pyo)2(OH2)](ClO4) were more prone to side reactions particularly to [(Bpy)(Cl)Ru(TpyPhTpy)Ru(Cl)(Bpy)](ClO4)2. Nonetheless, samples of both complexes exhibited catalytic activity comparable to the in-situ reactions validating the choice of targets. \ud \ud Finally, a simple theoretical study was carried out to calculate the relative stabilities of RuIIRuII, RuIIRuIII, and RuIIIRuIII oxidation states versus RuII and RuIII in monomers. At issue was the unusual observation that mixed valent RuIIRuIII intermediates were always observed during ketone transfer hydrogenation reactions with polypyridyl ruthenium catalysts though the alkaline alcohol environment should reduce RuIII to RuII. The results suggest that the mixed valent RuIIRuIII oxidation states were stabilized versus RuIII itself and were more likely to persist in a reducing environment. This lends some credence to the possibility that inner-sphere transfer hydrogenation requires RuIII which persists only in the dimer intermediates. \ud \ud Overall, the work described in this thesis confirms that bisterpyridine supported ruthenium dimers represent a new family of ketone transfer hydrogenation catalysts with promise as design platforms for customized selectivity