Transfer hydrogenation alcohol oxidation

Alcohols are used in large excess (e.g., as solvent) to shift the reaction to the desired product because, during the transfer, hydrogenation alcohols are oxidized to ketones or aldehydes that can compete with the substrate. The reaction is of the radical type, with the formation of radical intermediates obtained by abstracting a hydrogen atom from the a position to the hydroxyl group of individual alcohols (Brezova, Blazkova, Surina, Havlinova, 1997 Kaise et al., 1994). 

In the sixth chapter the activation of O-H bonds of water, alcohols and carboxylic acids, and their addition to multiple bonds is reported. Since the formally oxidative addition of ROH gives rise to hydrido(hydroxo) complexes, [MH(OR)Ln] which are postulated as intermediates in many important reactions (water gas shift reaction, Wacker-chemistry, catalytic transfer hydrogenations etc.) the authors of this chapter,... 

Alcohols have always been the major group of hydrogen donors. Indeed, they are the only hydrogen donors that can be used in Meerwein-Ponndorf-Verley (MPV) reductions. 2-Propanol (16) is most commonly used both in MPV reductions and in transition metal-catalyzed transfer hydrogenations. It is generally available and cheap, and its oxidation product, acetone (14), is nontoxic and can usually be removed readily from the reaction mixture by distillation. This may have the additional advantage that the redox equilibrium is shifted even more into the direction of the alcohol. As a result of sigma inductive electronic ef-... 

Alcohols will serve as hydrogen donors for the reduction of ketones and imi-nium salts, but not imines. Isopropanol is frequently used, and during the process is oxidized into acetone. The reaction is reversible and the products are in equilibrium with the starting materials. To enhance formation of the product, isopropanol is used in large excess and conveniently becomes the solvent. Initially, the reaction is controlled kinetically and the selectivity is high. As the concentration of the product and acetone increase, the rate of the reverse reaction also increases, and the ratio of enantiomers comes under thermodynamic control, with the result that the optical purity of the product falls. The rhodium and iridium CATHy catalysts are more active than the ruthenium arenes not only in the forward transfer hydrogenation but also in the reverse dehydrogenation. As a consequence, the optical purity of the product can fall faster with the... 

Numerous enantioselective transfer hydrogenation processes have now been developed and operated at commercial scale to give consistent, high-quality products, economically. These include variously substituted aryl alcohols, styrene oxides and alicyclic and aliphatic amines. Those discussed in the public domain include (S)-3-trifluoromethylphenylethanol [48], (f )-3,5-bistrifluorophenylethanol [64], 3-nitrophenylethanol [92], (S)-4-fluorophenylethanol [lc], (f )-l-tetralol [lc], and (T)-l-methylnaphthylamine [lc]. 

Keywords Alcohols Alkenes Asymmetric transfer hydrogenation C-alkylation Imines Ketones W-aUcylation Oxidation Reduction Transfer hydrogenation... 

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). 

Scheme 13 Enantioselective carbonyl tert-prenylation from the alcohol or aldehyde oxidation level via iridium-catalyzed C-C bond-forming transfer hydrogenation...

More recently, using the cyclometallated iridium C,(7-benzoate derived from allyl acetate, 4-methoxy-3-nitrobenzoic acid and BIPHEP, catalytic carbonyl crotylation employing 1,3-butadiene from the aldehyde, or alcohol oxidation was achieved under transfer hydrogenation conditions [274]. Carbonyl addition occurs with roughly equal facility from the alcohol or aldehyde oxidation level. However, products are obtained as diastereomeric mixtures. Stereoselective variants of these processes are under development. It should be noted that under the conditions of ruthenium-catalyzed transfer hydrogenation, conjugated dienes, including butadiene, couple to alcohols or aldehydes to provide either products of carbonyl crotylation or p,y-enones (Scheme 16) [275, 276]. 

Scheme 17 Carbonyl arylallylation from the alcohol oxidation level via iridium-catalyzed transfer hydrogenation employing alkynes as allyl donors...

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. 

Primary alcohols 121 undergo an efficient oxidative dimerization by [IrCl(coe)2]2 under air, without any solvent, to form esters 122 in fair to good yields (Equation 10.30) [54]. The reaction is initiated by the in situ generation of an Ir-hydride complex via hydrogen transfer from alcohols to afford aldehydes, followed by the dehydrogenation of hemiacetals derived from alcohols and aldehydes by action of the Ir-complex to afford esters. 

Some cation-radicals can appear as hydrogen acceptors. Thus, fullerene Cgg is oxidized to the cation-radical at a preparative scale by means of photoinduced electron transfer. As in the case of anion-radical, the fullerene Cgo cation-radical bears the highly delocalized positive charge and shows low electrophilicity. This cation-radical reacts with various donors of atomic hydrogen (alcohols, aldehydes, and ethers) yielding the fullerene 1,2-dihydroderivatives (Siedschlag et al. 2000). 

RuClj(C H )]j was used for deracemisation of alcohols, by oxidation of secondary alcohols to the ketone with [RuCl3(C H )]3/(R)-BINAP/(R,R )-DPEN/cyclo-hexanone/THF/K( BuO)/60°C. The oxidation may occur by transfer hydrogenation, followed by reduction with back to the alcohol [962],... 

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