Transfer hydrogenation of aldehydes

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]. 

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). 

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 highly efficient catalytic system for the chemoselective transfer hydrogenation of aldehydes was reported by Xiao et al. [52]. This system consisted of [Cp IrCl2]2 (1), a diamine and HCOONa, and worked on water and in air. A wide range of aromatic aldehydes were reduced to the corresponding primary alcohols in a highly chemoselective manner some representative examples are summarized in Table 5.9. 

Transfer hydrogenation of aldehydes with 2-propanol without the formation of side-products is described on a silica-supported Zr catalyst335. 

Iridium-monotosylated ethylenediamine [Ts(en)] and Ir-CF3Ts(en) are highly active and chemoselective catalysts for the aqueous-phase transfer hydrogenation of aldehydes using sodium formate as the hydrogen donor.376... 

In subsequent studies, Esteruelas et at disclosed the synthesis of another cationic complex, [(IPr)Os(OH)(p-cymene)][OTf] 52, which was an efficient pre-catalyst for transfer hydrogenation of aldehydes with isopropanol, for hydration of nitriles into amides, and for a-alkylation of arylacetonitriles and methyl ketones with alcohols (Scheme 7.10). All these transformations were assumed to involve cationic hydrido intermediates formed by hydrogen transfer from one of the substrates to the osmium active species. 

Scheme 6.12 Transfer hydrogenation of aldehydes with catalyst 13 in water.

Scheme 8.31 Transfer hydrogenation of aldehydes with Ir-PTsEN catalyst in emulsion system.

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. 

Molybdenum and tungsten carbonyl hydride complexes were shown (Eqs. (16), (17), (22), (23), (24) see Schemes 7.5 and 7.7) to function as hydride donors in the presence of acids. Tungsten dihydrides are capable of carrying out stoichiometric ionic hydrogenation of aldehydes and ketones (Eq. (28)). These stoichiometric reactions provided evidence that the proton and hydride transfer steps necessary for a catalytic cycle were viable, but closing of the cycle requires that the metal hydride bonds be regenerated from reaction with H2. 

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]. 

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). 

New catalytic allylation methodologies continue to emerge. For example, iridium-catalyzed transfer hydrogenation of a-(trimethylsilyl)allyl acetate in the presence of aldehydes mediated by isopropanol and employing the iridium catalyst... 

Various a,P-unsaturated aldehydes were also selectively reduced to give allylic alcohols by this catalytic system (Scheme 5.19). The transfer hydrogenation of ali-... 

Carbon-Nitrogen Bond Formation Based on Hydrogen Transfer 123 Table 5.9 Transfer hydrogenation of aromatic aldehydes with HCOONa in water. ... 

A possible mechanism for the P-alkylation of secondary alcohols with primary alcohols catalyzed by a 1/base system is illustrated in Scheme 5.28. The first step of the reaction involves oxidation of the primary and secondary alcohols to aldehydes and ketones, accompanied by the transitory generation of a hydrido iridium species. A base-mediated cross-aldol condensation then occurs to give an a,P-unsaturated ketone. Finally, successive transfer hydrogenation of the C=C and C=0 double bonds of the a,P-unsaturated ketone by the hydrido iridium species occurs to give the product. 

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