Hydrogenation reactions catalysed by organometallic complexes

In this thesis we have computationally studied two types of reduction processes which can be classified as asymmetric hydrogenation of ketones and reduction of imines. Density functional theory has been applied throughout the thesis. The reduction of acetophenone to phenylethanol catalysed by the trans- Ru(II)H2(diphosphine)(diamine) has been studied with an emphasis on the effect of the structure of the diphosphine and diamine ligands. The computed reaction pathways of the Ru(II)H2(diphosphine)[(S,S)-DPEN] catalysed reactions with different (S)-diphosphine ligands (XylBINAP, TolBINAP and BINAP) shows that the presence of two methyl groups in the meta position is critical to obtaining a high difference in activation energy for the reaction pathways associated with the (R)- and (S)-alcohols, and consequently high enantioselectivity. The effect of the diamine structure, while keeping the TolBINAP and XylBINAP fixed, has also been analysed. To enhance the enantioselectivity of the TolBINAP system, the addition of two methyl groups and the removal of a phenyl group on the diamine (DMAPEN) create the necessary steric interactions. We conclude this section by reporting a correlation between the enantiomeric excess and the difference in the computed activation energies along the two most favourable (S)- and (R)-reaction pathways, which shows that the computational procedure adopted could be used to predict the enantiomeric excess of ketone hydrogenation reactions catalysed by Noyori-type catalysts, and assist in the choice of ligands when optimising the enantiomeric excess. Calculations yield new insights into the structural, electronic and catalytic properties of the hydrogenation of ketones catalysed by the simplified Fe(II)H2(PH3)2(en) and real Fe(II)H2(diphosphine)(diamine) complexes. Calculations conducted using several different functionals on the trans- and cis-isomers of Fe(II)H2[(S)-XylBINAP][(S,S)-DPEN] complexes show that, as with the Ru(II)H2(diphosphine)(diamine) complexes, the trans- [Fe(II)H2(diphosphine)(diamine)] complex is the more stable isomer. Analysis of the spin states of the trans-[Fe(II)H2(diphosphine)(diamine)] complexes also shows that the singlet state is significantly more stable than the triplet and quintet states, as with the Ru(II)H2(diphosphine)(diamine) complexes. Calculations on the catalytic cycle for the hydrogenation of ketones using the two simplified trans-[M(II)H2(PH3)2(en)] catalysts, where M is either Ru or Fe, show that the mechanism of reactions as well as the activation energies are very similar, in particular: (a) the ketone/alcohol hydrogen transfer reaction occurs through the metal–ligand bifunctional mechanism, with energy barriers of 3.4 kcal/mol and 3.2 kcal/mol for the ruthenium- and iron-catalysed reactions respectively; (b) the heterolytic splitting reactions of H2 across the M=N bond for the regeneration of the ruthenium and iron catalysts have activation barriers of 13.8 kcal/mol and 12.8 kcal/mol respectively, and the heterolytic splitting steps are expected to be the rate-determining steps for both catalytic systems. The reduction of acetophenone by the trans- [Fe(II)H2{(S)-XylBINAP}{(S,S)-DPEN}] complexes along the two competitive reaction pathways shows that the intermediates for the iron catalytic system are similar to those responsible for a high enantioselectivity of (R)-alcohol in the trans-[Ru(II)H2{(S)- XylBINAP}{(S,S)-DPEN}] catalysed acetophenone hydrogenation reaction. Thus, the high enantiomeric excess in the hydrogenation of acetophenone could, in principle, be achieved using iron catalysts. In experimental work, Xiao and co-workers discovered cyclometalated iridium complexes in imine reduction with an unusually broad substrate scope, which shows that the more positive hydricity of iridium hydride affords a higher activity. To study these systems computationally, we initially tested parameters, including exchange-correlation functionals, basis sets and pseudopotentials, subsequently studying the charge and molecular orbital properties of isolated iridium(III) catalysts with different electrondonating and withdrawing functional groups, and investigating their mechanistic details. Three possible reaction pathways in the hydride formation step and six possible reaction pathways in the hydride transfer step have been suggested to locate transition states in both the gas phase and methanol solution. Our results show that hydride formation is the rate-determining step and with explicit methanol included in the reaction, the activation energies in the hydride formation and hydride transfer steps drop by ca. 10 and 4 kcal/mol respectively, compared with those computed in the gas phase.