Synthesis and study of ruthenium phosphine complexes for the catalytic hydrogenation of imines
Creators: name: Fogg, Deryn Elizabeth
Publisher: name: University of British Columbia
Year: 2009

description: Three classes of catalyst based on the "RuCl(PP)" (PP = chelating diphosphine) core have been prepared: dinuclear species containing two such moieties, and mononuclear complexes in which the remaining coordination sites are occupied by a potentially labile arene or nitrile ligand. High catalytic activity, and in some cases excellent enantioselectivity, have been demonstrated previously in olefin and ketone hydrogenation with several such complexes, but a systematic investigation, examining the effect of catalyst structure, had not been undertaken. Comparative studies focusing on activity toward imine hydrogenation were undertaken, as despite its synthetic importance the catalytic reduction of the C=N functionality remains largely undeveloped. A range of chiral (PP = diop, binap, chiraphos; see Figure 1) and achiral (PP = Ph₂P(CH₂)nPPh₂: n = 2; dppe, or 4; dppb) catalysts has been prepared, as shown in Figure 2. Efficient routes to the nitrile derivatives were developed for diphosphines forming a seven-membered chelate ring with the metal. Treatment of the readily accessible precursor RuCl₂(PP)(PPh₃) with nitrile, and a halide-abstracting agent where necessary, permits in a single step complete conversion to Ru₂Cl₄(PP)₂(RCN), Ru₂Cl₃(PP)₂(RCN) ₂⁺X⁻, RuCl₂(PP)(RCN)₂, RuCl(PP)(RCN)₃ ⁺X⁻ (X = CI, PF₆) or the dication Ru(PP)(RCN) ₄²⁺ 2PF₆-, which was characterised by X-ray crystallography (PP = dppb, R = Me). A complex series of equilibria relating these species in halogenated and nitrile solvents is elucidated. Synthetic routes to cationic arene species RuCl(C₆H₆)(PP) ⁺X⁻ were investigated, and two new, chiral complexes of this type were prepared (PP = chiraphos, diop). Improved syntheses, circumventing formation of bis(diphosphine) species t-RuCl₂(PP)₂, were devised for diphosphines forming a five-membered chelate ring. A very mild and potentially valuable route to the useful chiral catalyst RuCl(C₆H₆)(binap) ⁺X⁻ via the dmso adduct RuCl₂(C₆H₆)(dmso) was discovered; reaction of the dmso precursor with less bulky phosphines gave instead the phosphine-bridged complexes [RuCl₂(C₆H₆)]₂(μ-PP). [chemical compound diagrams] Most of the phosphine complexes shown in Figure 2 demonstrated high activity in the hydrogenation of imines at unusually low catalyst concentrations (ca. 0.77 mM Ru), permitting study of the catalysis under relatively mild conditions (room temperature and hydrogen pressures of up to 70 atm). The dinuclear complexes, in particular the air-stable and readily accessible Ru₂Cl₅ (PP)₂, were most active. Mechanistic studies using Ru₂Cl₅(dppb)₂ suggest that catalysis follows the unsaturate route, and imply a common catalyst species RuCl₂(PP)SS' (S = solvent, S' = solvent or imine) for the neutral complexes. The ability of these systems to effect asymmetric induction in prochiral ketimines was investigated. Consistent with the mechanistic work, enantioselectivities were essentially constant for a given phosphine within a neutral series of complexes (PP = binap or diop). These results imply a previously unrecognised basis for comparison of asymmetric hydrogenation data derived from structurally related catalyst systems, and highlight the importance of such comparative and mechanistic work as a means of establishing guidelines for catalyst design. The reactivity of the catalyst precursors Ru₂Cl₅(dppb)₂ and Ru₂Cl₄(dppb)₂ (as well as RuCl₂(dppb)(PPh₃), which generates the latter species in situ), toward imines was investigated. An imine adduct [RuCl(dppb)]₂[PhCH₂N=C(H)Ph] was identified; further substitution reactions (possibly yielding all-cis RuCl₂(dppb)[PhCH₂N=C(H)Ph]₂) are masked by the accessibility of an imine-hydrolysis pathway, which leads to the novel amine-bridged complex Ru₂Cl₄(dppb)₂(μ₂, η²-NH₂CH₂Ph), in which the amine ligand is proposed to coordinate by an agostic bond from a benzylic C-H group, as well as the nitrogen donor. Routes to this species from a number of imines, as well as benzylamine itself, were established, and the thermodynamic relationship between this complex and the less stable, terminal amine isomer was investigated. The generality of the amine-bridged coordination mode was established by preparation of analogous complexes of other primary amines (NH₂R; R = methyl, isopropyl, cyclohexyl, phenyl). Reactions with excess benzylamine were undertaken in order to assess the maximum extent of amine substitution; bis(amine) species were isolated and characterised, but cationic tris(amine) derivatives (analogous to the nitrile complexes described above) were not formed. Examination of the corresponding reactions with the secondary amine dibenzylamine suggested that amine dealkylation is facile, probably occurring via dehydrogenation of coordinated amine, followed by hydrolysis of the imine thus formed.