Synthesis Of Ruthenium Polypyridyl Complexes Research Articles

Reductive Labilization of a Cyclometalating Ligand Applied to Auxiliary-Mediated Asymmetric Coordination Chemistry

(4S)-4-Isopropyl-2-(3-nitrophenyl)-4,5-dihydrooxazole ((S)-Phox) is introduced as a novel chiral auxiliary for the asymmetric synthesis of ruthenium polypyridyl complexes. A simply accessible (S)-Phox-bearing precursor serves as the starting point for diastereoselective coordination chemistry: The stereogenic carbon atom of the cyclometalating auxiliary controls the spatial arrangement of incoming 1,10-phenanthrolines during ligand substitution reactions (ratio Λ:Δ up to 14:1), and further precipitation affords diastereopure compounds. In the following key step, the labilization of the auxiliary ligand is achieved by reduction, thus permitting its replacement against a third polypyridyl ligand with complete retention of the configuration at the metal center (er > 99:1) under mildly acidic conditions, in contrast with previously developed systems that require strong acid. On the basis of results of NMR experiments and X-ray analysis obtained for intermediate compounds, mechanistic considerations for the formation of diastereomeric complexes were made, revealing a Δ → Λ isomerization as the reason for the observed limitations in selectivity optimization. This work expands the pool of methods available for the asymmetric synthesis of tris-heteroleptic ruthenium polypyridyl complexes and additionally may serve as an inspiration for the synthesis of other nonracemic octahedral chiral-at-metal compounds.

Chiral-Auxiliary-Mediated Asymmetric Synthesis of Ruthenium Polypyridyl Complexes

An octahedral metal complex with 6 different monodentate ligands can form 15 diastereomers as pairs of enantiomers. As a result, the elaborate stereochemistry of octahedral coordination geometries provides tremendous opportunities in the fields of catalysis, the materials sciences, and the life sciences. The demand for enantiomerically pure coordination complexes for tasks related to the selective molecular recognition of biomacromolecules led us to develop synthetic methods to control the absolute stereochemistry at octahedral metal centers. A few years ago our laboratory therefore embarked on a project exploring new and general synthetic strategies for the asymmetric synthesis of inert octahedral transition metal complexes. We initially used the example of thermally inert ruthenium polypyridyl complexes and developed a family of chiral bidentate ligands, including salicyloxazolines, (mercaptophenyl)oxazolines, sulfinylphenols, N-acetylsulfinamides, a phosphinohydroxybinaphthyl, and even the amino acid proline to serve as chiral auxiliaries for asymmetric coordination chemistry. All these chiral auxiliaries strongly coordinate to ruthenium(II) in a bidentate, deprotonated fashion, allowing them to control the absolute metal-centered configuration in the course of subsequent ligand exchange reactions. Finally, we can remove them from the metal without any loss of chiral information and without leaving a chemical trace. A key feature of these chiral auxiliary ligands is their switchable binding strength. A chelate effect ensures that the chiral ligands coordinate very tightly to the metal center, placing their carbon-based, sulfur-based, or axial chirality in a well-defined position close to the metal center to efficiently establish the absolute metal-centered configuration. At the same time a coordinating phenolate, carboximidate, carboxylate, or thiophenolate moiety makes the coordination reversible by weakening the binding strength through protonation or methylation. Following this strategy, we synthesized a large number of homoleptic, bis-heteroleptic, and tris-heteroleptic ruthenium polypyridyl complexes in an asymmetric fashion with enantiomeric ratios that routinely reached or exceeded 96:4. Our approach should serve as a blueprint for the asymmetric synthesis of different classes of ruthenium complexes and chiral coordination complexes of other metals.

2-Diphenylphosphino-2′-hydroxy-1,1′-binaphthyl as a chiral auxiliary for asymmetric coordination chemistry

In this study, the bidentate ligand (R)-2-diphenylphosphino-2′-hydroxy-1,1′-binaphthyl (HO-MOP) was investigated as a chiral auxiliary for the asymmetric synthesis of ruthenium polypyridyl complexes. It was found that (R)-HO-MOP serves as an effective chiral auxiliary starting from different precursor complexes, most notably using the commercially available half-sandwich complex [Ru(η6-C6H6)Cl2]2.

Chiral Salicyloxazolines as Auxiliaries for the Asymmetric Synthesis of Ruthenium Polypyridyl Complexes

Chiral auxiliaries are promising emerging tools for the asymmetric synthesis of octahedral metal complexes. We recently introduced chiral salicyloxazolines as coordinating bidentate chiral ligands which provide excellent control over the metal-centered configuration in the course of ligand substitution reactions and can be removed afterward in an acid-induced fashion under complete retention of configuration (J. Am. Chem. Soc. 2009, 131, 9602-9603). Here reported is our detailed investigation of this sequence of reactions, affording virtually enantiopure ruthenium polypyridyl complexes. The control of the metal-centered chirality by the coordinated chiral salicyloxazolinate ligand was evaluated as a function of reaction conditions, the employed bidentate 2,2'-bipyridine and 1,10-phenanthroline ligands, and the substituent at the asymmetric 5-position of the oxazoline heterocycle. Most striking was the strong influence of the reaction solvent, with aprotic solvents of lower polarity providing the most favorable diastereoselectivities. Through a combination of computational and experimental results, it was revealed that the observed stereoselectivities are under thermodynamic control. The removal of the chiral salicyloxazoline auxiliary under retention of the configuration requires acidic conditions and a coordinating solvent such as MeCN or THF in order to prevent partial racemization. This method represents the first general strategy for the asymmetric synthesis of enantiopure heteroleptic ruthenium polypyridyl complexes.