Aldehydes transfer hydrogenations

For transition-metal-catalyzed hydrogenation of ketones and aldehydes, H2 or the combination of PrOH with a base has been widely used as the hydrogen source (Scheme 8). In case of using H2, the reaction is called hydrogenation, whereas the reaction using the combination of PrOH with a base is especially called transfer hydrogenation. ... 

Transfer hydrogenation of aldehydes with isopropanol without addition of external base has been achieved using the electronically and coordinatively unsaturated Os complex 43 as catalyst. High turnover frequencies have been observed with aldehyde substrates, however the catalyst was very poor for the hydrogenation of ketones. The stoichiometric conversion of 43 to the spectroscopically identifiable in solution ketone complex 45, via the non-isolable complex 44 (Scheme 2.4), provides evidence for two steps of the operating mechanism (alkoxide exchange, p-hydride elimination to form ketone hydride complex) of the transfer hydrogenation reaction [43]. 

The catalytic hydrosi(ly)lations of other C=X functional groups (X = O, NR) constitute alternative routes to the reduction of aldehydes, ketones, imines and other carbonyl compounds (Scheme 2.9), circumventing the use of molecular hydrogen or occasionally harsh transfer hydrogenation conditions. 

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

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

Gordon used a household microwave oven for the transfer hydrogenation of benz-aldehyde with (carbonyl)-chlorohydridotris-(triphenylphosphine)ruthenium(II) as catalyst and formic acid as hydrogen donor (Eq. 11.43) [61]. An improvement in the average catalytic activity from 280 to 6700 turnovers h-1 was achieved when the traditional reflux conditions were replaced by microwave heating. 

Fig. 15.5 Transfer hydrogenation of aldehydes using [Rh(COD)CI]2/TPPTS at 80°C using i-PrOH as hydrogen donor. Values shown are yields (TOF, h 1).

The water-soluble ligand (TPPTS) was discussed earlier with regard to aldehyde reduction [17]. Similarly, in ketone transfer hydrogenation, high yields are obtained for a variety of substrates with the ability for efficient catalyst recycling at no expense of activity or selectivity (Fig. 15.10). 

Aldehydes may sometimes pose a problem in transfer hydrogenations catalyzed by transition metals. They can poison the catalyst or decarbonylate, forming CO, which may coordinate to the metal complex and result in a change in activity (Scheme 20.26) [65, 66]. 

Transfer hydrogenation is a mild and efficient means of reducing aldehydes, and can be advantageous over other reagents such as sodium borohydride. Clearly, the product is a primary alcohol and therefore not chiral, but a chiral center might be alpha to the aldehyde, in which case a resolution can be effected. Indeed, under the appropriate conditions the chiral center can be race-mized and a dynamic kinetic resolution effected [57]. 

The Meerwein-Ponndorf-Verley reaction is a classic method for ketone/ aldehyde carbonyl group reduction, which involves at least 1 equivalent of aluminum alkoxide as a promoter. In this reaction, the hydrogen is transferred from isopropanol to the ketone/aldehyde substrate, so the reaction can also be referred to as a transfer hydrogenation reaction. 

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]. 

Scheme 11 Carbonyl tert-prenylation, crotylation, and allylation from the aldehyde or alcohol oxidation level under the conditions or iridium-catalyzed transfer hydrogenation...

SEGPHOS [271, 272]. Using this complex as a precatalyst, transfer hydrogenation of 1,1-dimethylallene in the presence of diverse aldehydes mediated by isopropanol delivers products of ferf-prenylation in good to excellent yield and with excellent levels of enantioselectivity. In the absence of isopropanol, enantio-selective carbonyl reverse prenylation is achieved directly from the alcohol oxidation level to furnish an equivalent set of adducts. Notably, enantioselective ferf-prenylation is achieved under mild conditions (30-50°C) in the absence of stoichiometric metallic reagents. Indeed, for reactions conducted from the alcohol oxidation level, stoichiometric byproducts are completely absent (Scheme 13). 

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