Ketones outer-sphere mechanism

Scheme 4. (a) Inner-sphere and (b) outer-sphere mechanisms for ketone hydrogenation. 

Fig. 4. Energy profiles in THF for both concerted pathways at B3LYP level for the hydrogenation of ketones by the Shvo s catalyst. Inner-sphere mechanism dashed fine outer-sphere mechanism solid line.

Fig. 5. Transition-states of the concerted outer-sphere mechanism for the hydrogenation of ketones in both the model (left) and complete (right) Shvo s catalysts.

The identity of active catalytic species for the TH of ketones with our iron carbonyl [6.5.6]-P-N-N-P complexes was still unclear. Did the imine or imines on the ligand get reduced in situ, allowing catalysis to occur through a bifunctional outer sphere mechanism, as seen with the analogous ruthenium systems This question drove us to further investigate the mechanism of transfer hydrogenation with our first generation [6.5.6]-P-N-N-P systems. 

Outer-Sphere Mechanism for the Hydrogenation of Ketones and Imines... 

The mechanism of hydrogen transfer to ketones, catalysed by Knolker s iron complex (29) (TMS = trimethylsilyl), has been studied by applying DFT calculations to a semi-simplified system for two inner-sphere mechanisms and three outer-sphere mechanisms. An outer-sphere mechanism involving a concerted hydrogen transfer to the substrate is found to be the most kinetically feasible. The real system had a higher free energy barrier because of the steric effect of the substituent group. 

The formation of diastereomeric product 67 from the substrate E)-65 is plausibly rationalized by a twofold inversion firstly in the formation of the Jt-complex 66 and secondly by an approach of the nucleophilic enolate. In this case, there is no need for a thermodynamically controlled (Z)- to ( )-interconversion, and thus, a net retention in the allylic alkylation results (Scheme 5.22). Analogous stereochemical outcome was observed for the reaction of the lithium enolate of cyclohexanone with the allylic substrates (Z)-60 and ( )-65. The results shown in Schemes 5.21 and 5.22 clearly prove the outer-sphere mechanism for the Tsuji-Trost reaction of ketone lithium enolates [16c]. 

Noyori and coworkers reported well-defined ruthenium(II) catalyst systems of the type RuH( 76-arene)(NH2CHPhCHPhNTs) for the asymmetric transfer hydrogenation of ketones and imines [94]. These also act via an outer-sphere hydride transfer mechanism shown in Scheme 3.12. The hydride transfer from ruthenium and proton transfer from the amino group to the C=0 bond of a ketone or C=N bond of an imine produces the alcohol or amine product, respectively. The amido complex that is produced is unreactive to H2 (except at high pressures), but readily reacts with iPrOH or formate to regenerate the hydride catalyst. 

An interesting catalytic ruthenium system, Ru(7/5-C5Ar4OH)(CO)2H based on substituted cyclopentadienyl ligands was discovered by Shvo and coworkers [95— 98]. This operates in a similar fashion to the Noyori system of Scheme 3.12, but transfers hydride from the ruthenium and proton from the hydroxyl group on the ring in an outer-sphere hydrogenation mechanism. The source of hydrogen can be H2 or formic acid. Casey and coworkers have recently shown, on the basis of kinetic isotope effects, that the transfer of H+ and TT equivalents to the ketone for the Shvo system and the Noyori system (Scheme 3.12) is a concerted process [99, 100]. 

For the unusual reactivity of ferrocenylsilanes toward 5u in THF, affording ketones instead of the expected tertiary alcohols, a mechanism was proposed including the inner-sphere electron transfer from 5u within a reactant complex. The proposition was based on an electrochemical CV examination, which indicated that the outer-sphere process is thermodynamically unfavorable. 

Nevertheless, the mechanism of the Shvo s catalyst has been one of the most controversial regarding the nature of the hydrogen-transfer process (84). The analysis of this reaction mechanism served as an example of comparison of both the inner- and outer-sphere reaction pathways for hydrogenation of polar, C=0 (85-87) and C=N (88—95) and unpolar bonds (95). In the next subsections are presented the mechanistic studies we carried out for the hydrogenation of ketones, imines, alkenes, and alkynes (29,87,95). 

Further work by Flowers examined the role of solvent polarity in the electron transfer process.30 Inner-sphere electron transfer kinetics show a weak dependence on solvent polarity due to the considerable orbital overlap of the donor-acceptor pair in the transition state. In an outer-sphere process, changes in solvent polarity alter the energetics of electron transfer. The addition of excess HMPA, beyond that required to saturate Sml2, resulted in a linear correlation to the rate of reduction for alkyl iodides, whereas no impact was observed on the rate of ketone reduction.30 Thus the experiments showed a striking difference in the electron transfer mechanism for the substrate classes, which is consistent with the operation of an outer-sphere-type process for the reduction of alkyl iodides and an inner-sphere-type mechanism for the reduction of ketones.30 These findings are consistent with the observations of Daasbjerg and Skrydstrup.28,29... 

A refinement of the mechanism was searched for in the more recent literature when a differentiation was made between what was called inner-sphere ET and outer-sphere ET. It was assumed that, in the reaction of a Grignard reagent with a ketone (i.e., benzophenone), the electron transfer was rate-limiting [44] furthermore, for a series of Grignard reagents, a correlation had been found between the reaction rates and their oxidation potentials [21], according to the Marcus theory for outer-sphere ET [55]. Nevertheless, it seemed questionable [56] whether the electron transfer was an independent step (steps l->2->3-+4 in Scheme 19), or whether it was concerted with the transfer of the magnesium atom (steps l->3->4). 

Transition metals in a high oxidation state are often capable of extracting an electron from electron-rich organic substances. Ketones, esters, nitriles and various other carbon acids that can form enols, enolates and related structures are by far the most commonly used substrates. Their oxidation can lead to a free radical, which then follows one or more of the pathways deployed in Scheme 8.3. Its important to take into account that the rate of radical production will depend on the exact structure of the substrate, its propensity to exist as the corresponding enol or enolate in the medium, the pH, the solvent, the temperature and, of course, the redox potential of the metallic salt (which can be strongly affected by the nature of the ligand around the metal) and the exact mechanism by which electron transfer actually occurs (i.e. inner or outer sphere)... 

A series of molybdenum and tungsten catalysts for the hydrogenation of ketones have been reported by Bullock (101,102). These catalysts operate by an outer-sphere ionic mechanism. The reaction occurs by proton transfer from a cationic metal dihydride (or a metal dihydrogen species), followed by hydride transfer from a neutral metal hydride to a ketone (Fig. 34). 

In this species, there is no direct coordination of the ketone to the Ru, but rather an outer-sphere association with an orientation of the ketone such that two H atoms can be transferred from the 18-electron hydride, one coming from the hydridic H and the other from the NHj group. This nonclassical mechanistic pathway is now widely accepted for this class of catalysts and is referred to as metal-ligand bifunctional catalysis. Theoretical work of Andersson and co-workers and Noyori et al. provided support for the mechanism and further details are discussed in a review by Noyori et al. ... 

Scheme 1.45 A revised catalytic cycle for the asymmetric hydrogenation of aromatic ketones in propan-2-ol by Noyori s (pre)catalyst 1 based on a computed MEp253 follows a H /H" " outer sphere hydrogenation mechanism (see text). KO-f-C4H9 free conditions X = Y = H. Under high KO-f-C4H9 concentration X = Y = K and/or H. Formation of the major enantiomeric product is shown. (Adapted from Dub, P. A. et al., /. Am. Chem. Soc., 136, 3505-3521. Copyright 2014 American Chemical Society.)...

Kndlker s catalyst (151) catalyses hydrogenation of ketones, and DFT calculations have identified five plausible mechanisms two inner- and three outer-sphere. One of the latter proved most viable, with the lowest free energy barrier, and also was consistent with kinetic results for acetophenone. It involves simultaneous proton and hydride transfer and suggests that further improvement will require simultaneous increase in polarization of CpO-H and Fe-H bonds. 

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