Isopropanol, as hydrogen source

A series of chiral N,S-chelates was synthesized as ligands for the iridium(l)-catalyzed reduction of ketones using either HCOOH/NEtj or isopropanol as hydrogen sources. The ligands were obtained by sulfoxidation of an (R)-cysteine-based aminosulfide, providing a diastereomeric ligand family containing a chiral sulfur... 

Chaudret and coworkers have studied the activity of chiral aminoalcohol- and oxazoline-stabilized Ru colloids in the hydrogen transfer reaction (Scheme 11.8) [44]. The reduction of acetophenone has been studied using isopropanol as hydrogen source and preformed nanocatalysts under basic conditions and at room temperature (Table 11.10). 

Hydrogen transfer reactions consist of formal transfers of two hydrogen atoms from a hydrogen donor to a prochiral substrate, catalysed by ruthenium(II) complexes under basic conditions. The model substrate for hydrogen transfer of ketones is once again acetophenone with isopropanol as hydrogen source and potassium tcrt-butoxide or KOH as base (Scheme 7.18). 

A number of donor-functionalized NHC-based iridium complexes have been tested in the transfer hydrogenation of ketones using isopropanol as hydrogen source. Good to excellent conversions in the transfer hydrogenation of acetophenone to 1-phenylethanol were obtained using 46 [68b] and 47 [69], while amine-NHC Ir(III) complexes 48 described by Morris and coworkers afforded lower activities in the same reaction [68a]. 

Several other versions of these catalysts have been developed. Arene complexes of monotosyl-l,2-diphenylethylenediamine ruthenium chloride give good results with a,(3-ynones.55 The active catalysts are generated by KOH. These catalysts also function by hydrogen transfer, with isopropanol serving as the hydrogen source. Entries 6 to 8 in Scheme 5.3 are examples. 

Samec and Backvall found that the dinuclear Shvo complex catalyzes the transfer hydrogenation of imines using benzene as solvent and isopropanol as the hydrogen source (Eq. (45)) [76]. These catalytic hydrogenations were typically carried out at 70 °C, and gave >90% yields of the amine in 4 h or less. 

Enantioselective reduction of acetophenone was achieved in a ruthenium-catalysed hydrogen transfer reaction using isopropanol as the hydrogen source in the presence of mono-tosylated (R, R)-diphenylethylenediamine, ephedrine or norephedrine as chiral auxiliary ligands. Under optimised conditions, ( R)-l-phenylethanol was obtained in 90% yield and 82% enantiomeric excess (ee) within 9 min. f-Butylphenylketone was reduced under similar conditions in almost quantitative yield but in moderate ee... 

The direct conversion of alkenes 337 to secondary alcohols 341 was also achieved using an excess of sacrificial secondary alcohol, such as isopropanol, as the hydrogen source (entry 14) [392-394]. Although the mechanistic details are not completely understood, it is likely that the reaction follows a similar course involving hydrocobaltation/oxygen trapping and reduction (see below). In addition to products 341 and the corresponding ketones, which were formed in similar ratios as before, 2 equiv. of water were also detected. 

For the asymmetric reduction of tiglic acid (21) to 2-methyl-butanoic acid (22), isopropanol can also be used as the hydrogen source. In the presence of H4Ru4(CO)8(f ,R-DIOP)2 at 120°C, 42% of 21 was converted after 227 hr, giving R-22 (catalytic turnover 210) with 5.4% optical purity (cf. Scheme 4) 133). 

Isopropanol (and other secondary alcohols) are eilso excellent electron sources when used with Ru, Pd and Rh as electron mediators. After donating two electrons and two protons (ie. a hydrogen equivalent) the secondary alcohols are converted into ketones. The ketones are readily reduced back to the secondary alcohols by catalytic hydrogenation and recycled. Using secondary alcohols will therefore add an extra step to the process but they are safe in the presence of oxygen. Thus secondary alcohols can be considered as safe sources of hydrogen. 

Other sources of hydrogen can be used instead of elemental hydrogen gas. In transfer hydrogenations a secondary alcohol has been employed as hydrogen donor. Noyori et al. have also made advances in this field. They use a catalyst system from [RuCbC -mesitylene)]2, iV-(p-toluenesulfo-nyl)-l,2-diphenylethylenediamine, and KOH in isopropanol. At room temperature acetophenone can be reduced in 15 h with this complex prepared in situ (substrate catalyst = 200 1) to 1-phenylethanol in 95% yield with an optical purity of 97 %. [15, 16] The... 

In contrast, Bianchini has observed the C=0 hydrogenation of benzylidene-acetone with (P3P)M(H)(H2) (M = Fe, Ru, Os) catalysts. When run as a transfer hydrogenation (discussed in the next section) with isopropanol as the ultimate source of (but allowing the pressure to vary), the catalytic activity proved to depend inversely on pressure — suggesting that competes with the ketone for a coordination site (eq 55) [96]. This process is examined in greater detail in Chapter 9. 

Enantioselectivities up to 56% ee were obtained using [Ir(COD)Cl]2 associated with fluorous diimines 3a-3c at 70 °C in the reduction of acetophenone with isopropanol as the hydride source in the presence of Galden D-lOO (mainly n-perfluorooctane, b.p. 102 °C) as the fluorous solvent. The hydrogen-transfer reduction was extended to other ketones, enantioselectivity of 60% ee being obtained... 

Yet another interesting application of complex 51 [109] was described by us in the context of transfer hydrogenation processes. Compound 51 was found to be active in the reduction of CO2 to formate using isopropanol as the hydrogen source (Equation 10.1) [110]. This unprecedented reaction is interesting because it uses an inexpensive and environmentally friendly hydrogen source and provides an easy access to formic acid and sodium formate. 

Aydemir and co-workers used chiral aminoalcohols to prepare phosphinites 118a-b (Scheme 30), through the reaction of the aminoalcohols with ferrocene carboxaldehyde, followed by reaction with chlorodiphenylphosphine. The ligands were tested in ruthenium(ii)-catalysed transfer hydrogenation of acetophenone derivatives, using isopropanol as the hydrogen source, with high conversions and enan-tioselectivities of up to 85% ee. 

This reaction is the reverse of the initial ketyl radical formation by the benzophenone triplet and is therm Q4ynamically favorable. The experiments using optically active alcohols as source of hydrogen atoms show, however, that under normal conditions this reaction is unimportant. This is probably due to other, more efficient pathways for reaction of the ketyl radicals or perhaps to diffusion rates which separate the radicals before reverse transfer can occur. That this reaction can be important in some cases even without the presence of sulfur compounds was shown by studying the photoreduction of benzophenone in optically active ethers.<68) Although the reaction of benzophenone in methyl 2-octyl ether is only 0.17 times as fast as that in isopropanol, ethers can be used as sources of hydrogen atoms for photoreduction ... 

In many reactions molecular hydrogen may be replaced by other H-sources such as methanol, isopropanol, or formic acid even cyclic ethers such as dioxane or THF can be used in homogeneous transfer hydrogenation. The hydrogen donor coordinates to the metal and undergoes /3-hydrogen transfer ... 

The use of secondary alcohol for activating redox composite catalysts in hydrocarbon autoxidations is attractive. Isopropanol is excellent as an electron source. Acetone will be produced as the byproduct in these autoxidations. It is easily separated and reduced back to isopropanol by catalytic hydrogenation and recycled. 

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