Cyclohexanone transfer hydrogenation

Pioneering studies on a different class of transfer hydrogenation catalysts were carried out by Henbest et al. in 1964 [15]. These authors reported the reduction of cyclohexanone (4) to cyclohexanol (5) in aqueous 2-propanol using chloroiridic acid (H2IrCl6) (6) as catalyst (Scheme 20.2). In the initial experiments, turnover frequencies (TOF) of 200 h 1 were reported. 

The same catalyst has also been used for the reduction of aldehydes to primary alcohols [7]. Several other iridium W-heterocyclic carbene complexes have been shown to be successful as catalysts for the transfer hydrogenation of ketones [8-12], including the interesting complex 6, where the cyclopentadienyl ring is tethered to the 77-heterocyclic carbene. Complex 6 was employed at low catalyst loading for the reduction of a range of ketones including the conversion of cyclohexanone 11 into cyclohexanol 12 [13]. 

The catalyst is also effective for the reduction of styrenes, ketones, and aldehydes. Cyclohexenone 16 was reduced to cyclohexanone 11 by transfer hydrogenation, and using a higher catalyst loading, styrene 17 was reduced to ethylbenzene 18. The elaboration of [Ir(cod)Cl]2 into the triazole-derived iridium carbene complex 19 provided a catalyst, which was used to reduce aUcene 20 by transfer hydrogenation [25]. 

Excellent enantioselectivity was achieved for the transfer hydrogenation of pinacolone by using (S)-25a as a catalyst with 2-propanol in the presence of (CH3)2CHONa to give the S alcohol in >99% ee (Scheme 28) [90], 2,2-Dimethyl-cyclohexanone was reduced with the same catalyst with 98% optical yield. Reduction of cyclohexyl methyl ketone with (S)-25b gave the S alcohol in 66% ee. 

The pincer rhodium(III) complex was successfully employed in the transfer hydrogenation of cyclohexanone, acetophenone and benzophenone with isopropyl alcohol as... 

In a first model reaction, Danopoulos et al. [472] reacted a free pincer carbene ligand with [RuCPPhjljCl ] and obtained the corresponding octahedral pincer carbene adduct (see Figure 3.156). The complex lacks the yhdene functionality necessary for activity of the complex in olefin metathesis. Instead, the compound was successfully employed in the transfer hydrogenation of cyclohexanone, acetophenone and benzylidene anihne. Reaction temperatures were mostly low to moderate (25-55 °C) and catalyst loadings in the range of 0.015 to 0.1% with TONs of only 150 to 8800. 

Wismeijer et al. studied the liquid-phase transfer-hydrogenation of 4-tg/t-butyl-cyclohexanone by z-PrOH at 83 °C over activated y-Al203 as the catalyst [5]. The activity of the catalyst was found to increase with increasing activation temperature. Selective poisoning experiments indicated that co-ordinatively unsaturated Al surface ions (Lewis acid sites), formed upon dehydroxylation, were essential... 

Cyclohex-2-en-l-one was converted initially to cyclohexanone but this was subsequently reduced at a rate comparable to the rate of appearance of the cyclohexanol e.g. after 30 min there was 40% reduction of the enone to equal amoimts of the saturated ketone and alcohol, while after 48 h there was 73% conversion of enone to essentially just cyclohexanol - no cyclohexen-l-ol was detected (10). Nitrobenzene was reduced selectively to aniline, but the conversion was only 20% after 48 h, while 4-nitrobenzaldehyde gave a mixture of mainly nitrobenzyl alcohol and smaller amounts of aminobenzyl alcohol and the aminobenzaldehyde. Heptan-l-al was also reduced to heptan-l-ol, while benzaldehyde under such basic conditions imderwent the Cannizzaro reaction to give the alcohol and benzoate. The findings summarized in this paragraph are all reproducible, while a notable transfer hydrogenation of oct-l-ene to octane noted in the earlier commimication has not been duplicated this will be commented on later. 

The bifunctional complexes 29 and 30 demonstrated low activities in transfer hydrogenations of acetophenone and cyclohexanone (Scheme 32). For instance, the reaction of acetophenone in 2-propanol catalyzed by 0.45 mol% of complex 29 afforded within 1 h a 50% conversion corresponding to a TON value of 109. A maximum conversion of 66% was eventually achieved reaching the equilibrium state between acetophenone and 1-phenylethanol. The transfer hydrogenation of cyclohexanone catalyzed by 0.33 mol% of complex 30 afforded within 65 min a conversion of 54% corresponding to a TON of 162. The low TON values were attributed to the decomposition of the catalyst due to the instability of 30 in 2-propanol. 

KO Bu as base. The preformed Ru hydride 27a was similarly inactive in the absence of added KO Bu, although 94% conversion was obtained in the hydrogenation of cyclohexanone when using 2mol% KO Bu (entry 6, Table 6.1). These preliminary results estabhsh the catalytic utility of such (PSiP) Ru" complexes in ketone transfer hydrogenation. 

Reactions of the phosphoranimine-phosphine ligand (55) with the ru-thenium(II) complexes Ru(f/ -arene)(/i-Cl)Cl2 afford the neutral complexes (56a f) with metalligand coordination at the phosphine phosphorus. These complexes can be transformed in the cationic complexes (57a f) by treatment with AgSbFg. Both the neutral and cationic complexes have been used as catalysts in the transfer hydrogenation of cyclohexanone by 2-propanol. All complexes appear to be efficient catalysts, the most active being (571). ... 

Efforts to cleave the S-Ru bond by an excess of NaX failed, demonstrating a greater stability of this bond when compared with the 0-Ru, which is in accordance with the soft character of the metal atom. Investigations of the catalytic activity of these complexes in the transfer hydrogenation of cyclohexanone by 2-propanol reveal all complexes to be active and efficient catalysts with a higher activity for the Ru(IV) compounds compared to the corresponding Ru(II) compounds. ... 

A cationic half-sandwich complex of ruthenium containing a l-(2-methylpyridine)phosphole as ligand (Fig. 64) is a very efficient catalyst for the transfer hydrogenation of cyclic ketones such as cyclohexanone and syn-2,5-dimethyl cyclohexanone, as well as acetophenone, benzophenone, and 2-acetylpyrodine, in basic 2-propanol. TOFs in the 1.03x 10 to 1.33x 10 h range, at complete conversion, were achieved (268). 

Several studies have been published on neutral and cationic half-sandwich (aiene)Ru(II) derivatives containing differently substituted pyrazoles and pyrazolates [9], and also pyrazole-phosphinite ligands, together with preliminary tests on their catalytic activity in transfer hydrogenation of cyclohexanone by propan-2-ol [10]. 

These mechanistic interpretations can also be applied to the hydrogenation of cyclohexanones. In acid, the carbonium ion (19) is formed and adsorbed on the catalyst from the least hindered side. Hydride ion transfer from the catalyst gives the axial alcohol (20). " In base, the enolate anion (21) is also adsorbed from the least hindered side. Hydride ion transfer from the catalyst followed by protonation from the solution gives the equatorial alcohol (22). 

Ir(cod)Cl]2 reacts with Q-diimines LL (derived from glyoxal and biacetyl) to yield cationic [Ir(cod)LL]+.523 If the reaction is carried out in the presence of SnCl2, then the pentacoordinate Ir(SnCl3)(cod)LL species results. The compounds are active catalysts in the homogeneous hydrogen transfer from isopropanol to cyclohexanone or to acetophenone followed by hydrogenation... 

Cyclohexanones undergo type I cleavage to produce a mixture of ketenes and aldehydes by hydrogen transfer,<1-3)... 

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