Hydrogen transfer to ketones

The competition between insertion and hydrogen transfer is also crucial to the selectivity of the reaction of aluminium alkyls with carbonyl compounds. Aluminium alkyls, like organolithium compounds and Grignard reagents, can add to aldehydes and ketones to form secondary or tertiary alcohols, respectively. If the aluminium alkyl has a j -hydrogen, however, reduction of the carbonyl compound is a common side reaction, and can even become the main reaction [16]. Most authors seem to accept that reduction involves direct j5-hydrogen transfer to ketone. 

Hydrogen transfer to ketones from 2-propanol was developed into an extremely efficient method of obtaining secondary alcohols [256,257] and the use of chiral N-(p-tolylsulfonyl)diamines allow the reduction of prochiral ketones with extraordinary stereoselectivity [257-259], In general, water is not well tolerated in such processes, and several studies showed that both the rate and the enantioselectivity of transfer hydrogenations from 2-propanol decrease substantially in increasingly aqueous mixtures even in the presence of water soluble catalysts [260,261], However, in a recent study the opposite effect was found. Using the water soluble Rh- and Ir-complexes... 

Several groups have investigated the synthesis of such compounds, for instance the cationic metallo-macrocycles [(t -ring)M(Aa)]3[BF4]3 (Aa = amino acidate) act as catalysts for hydrogen transfer to ketones while the neutral metallo-macrocycles [( -ring)ML]3 are efficient hosts for alkali metals (Li and Na). However, the chiral aspect of these species in solution was not investigated and only Yamanari and coworkers have reported diastereomeric separations, but no NMR studies have been made to differentiate these chiral macrocycles by the use of a chiral auxiliary. Recently the chemistry of these macrocycles was reviewed by Severin, who contributed largely to the development of this field. 

The mechanism of hydrogen transfer to ketones, catalysed by Knolker s iron complex (29) (TMS = trimethylsilyl), has been studied by applying DFT calculations to a semi-simplified system for two inner-sphere mechanisms and three outer-sphere mechanisms. An outer-sphere mechanism involving a concerted hydrogen transfer to the substrate is found to be the most kinetically feasible. The real system had a higher free energy barrier because of the steric effect of the substituent group. 

The order of quenching rate constants of triplet-excited azoalkanes and ketones cannot solely be explained on basis of energy transfer processes. Hydrogen abstraction from olefins and dienes plays a role as well, especially for double allylic systems such as 1,4-cyclohexadiene [206]. The resulting bis-aUylic radicals are highly stabilized, thus, hydrogen transfer to ketones and azoalkanes is thermodynamically favored. The superior reactivity of the stronger electron acceptor benzophenone can be partly... 

Hasegawa, T., Yamazuki, Y, and Yoshioka, M., Photocyclisation via remote hydrogen transfer to ketone carbonyl oxygen. Trends Photochem. Photobiol, 4, 27-41, 1997. 

The selective oxidation and, more generally, the activation of the C-H bond in alkanes is a topic of continuous interest. Most methods are based on the use of strong electrophiles, but photocatalytic methods offer an interesting alternative in view of the mild conditions, which may increase selectivity. These include electron or hydrogen transfer to excited organic sensitizers, such as aryl nitriles or ketones, to metal complexes or POMs. The use of a solid photocatalyst, such as the suspension of a metal oxide, is an attractive possibility in view of the simplified work up. Oxidation of the... 

A. Ruthenium Catalyzed Asymmetric Transfer Hydrogenation (ATH) TO Ketones... 

The greater stability of simple ketones relative to their enol tautomers is reversed on formation of the corresponding radical cations (88a) (88b). In appropriate cases, ionization of the ketone to its cation is followed by spontaneous hydrogen transfer to give the enol radical cation. 1,5-Hydrogen transfer via a six-membered-ring transition state is a common route. Characterization of such mechanisms has been reviewed for a variety of such reactions in cryogenic matrices, where many of the processes that compete in solution are suppressed. ... 

Ruthenium compounds are widely used as catalysts for hydrogen-transfer reactions. These systems can be readily adapted to the aerobic oxidation of alcohols by employing dioxygen, in combination with a hydrogen acceptor as a cocatalyst, in a multistep process. For example, Backvall and coworkers [85] used low-valent ruthenium complexes in combination with a benzoquinone and a cobalt Schiff s base complex. The proposed mechanism is shown in Fig. 14. A low-valent ruthenium complex reacts with the alcohol to afford the aldehyde or ketone product and a ruthenium dihydride. The latter undergoes hydrogen transfer to the benzoquinone to give hydroquinone with concomitant... 

Intramolecular hydrogen-transfer to a nearby free-radical is a general phenomenon (see Chapter 10) and in a diradical (13) can, in principle, occur in either of the two ways depicted, to give either (a) a non-conjugated unsaturated aldehyde (14), or (b) a ketene (15). In the C-nor-ketone 12) hydrogen transfer... 

As noted above (Section 1.4.2.2) reduction of carbonyl compounds under these conditions proceeds with hydrogen transfer to afford an equimolar mixture of alkoxide and enolate, plus varying quantities of dimeric reduction products. As a consequence, at least in theory, this procedure should afford an equimolar mixture of recovered ketone and reduction product. This appears to be the case if less than one equivalent of metal is used however, with excess metal, camphor, " some 12-keto steroids2 and several 1 -decalones2 afforded 70-99% yields of secondary alcohols. The explanation which has been offered is that the product enolate is protonated by NH3 to regenerate the starting ketone, which is recycled through the reduction process. ... 

UV absorbers (UVA) act by absorbing UV light to retard the photolysis of hydroperoxides. Typical examples are based on 2-hydroxybenzophenones (AO 28) and 2-hydroxybenzotriazoles (e.g.. Table 1, AOs 29-32) both are photo-stable with high molar absorptions over the region 300-360 nm. Their activity is based essentially on absorption of the harmful UV-radiation and its harmless dissipation as heat. For example, in 2-hydroxybenzophenones, UV-light induces intramolecular hydrogen transfer to yield an enol, which reverts back to the original ketone in a radiationless process, Reaction 4. 

It has also been suggested2 that secondary alcohol formation in the absence of added proton donors may occur by hydrogen transfer from ketone, rather than from one ketyl unit to another. 

Excitation of the ketone (226) brings about a 1,7-hydrogen transfer to afford the biradical intermediate (e.g., 227). Cyclization within this species yields the alkenyl-tetrahydrofurans (228) and (229) in the yields and ratios shown. The cyclization process is reasonably selective in that the geometry of the double bond is retained in the cyclized product. This was demonstrated for the enone (230) (a cis trans mixture of ratio 1 3), which gave the cyclized products (231—234) (Scheme 16). Two principal products (235, 15%) and (236, 60%) are obtained from irradiation of the ketone (237) in dioxan solution. " Two minor products (238)... 

Additional catalyst development identified the positive effect of 1,2-diamines as additives in the (BlNAP)Ru(OAc)2-catalyzed enantioselective hydrogenations of ketones [24], This discovery ultimately led to the synthesis of a class of (diphosphine) Ru(diamine)X2 (X = H, halide) compounds [25] (Figure 4.1) which have emerged as some of the most active and selective hydrogenation catalysts ever reported [26]. Mechanistic studies by Noyori [14] and Morris [27] have established bifunctional hydrogen transfer to substrate from the cis Ru-H and N-H motifs and identified the importance of ruthenium hydridoamido complexes for the heterolytic splitting of H2. This paradigm allows prediction of the absolute stereochemistry of the chiral alcohols produced from these reachons. 

An asymmetric hydrogen transfer of ketones was reported using chiral perfluorinated ligands in a 2-propanol/n-perfluooctane biphasic system. Several perfluorinated salen and diamine ligands were examined for the reaction catalyzed by the [Ir(COD)Cl]2 complex diamine 16 was found to be most effective (Scheme 20). The reaction was carried out at 70" C for 30 min and then the mixture was cooled to 0°C. The perfluorooctane solution was separated and used for the next reaction. The reactivity was almost the same as that of the first mn, and the enantioselectivity was higher (79% ee). Two further recyclings of the fluorous layer yielded the product with enantioselectivities up to 59% ee, but a decrease in activity was observed. 

Compounds of the general tape 110, with a variety of substituents all give an efficient singlet decarbonylation. 83) Ketone 111 gives an efficient carbon monoxide expulsion 4) (the hydrogen transfer to 112 is intramolecular) in contrast with 114, which only decarbonylates slug-... 

As was the case with a-keto acids and esters, there are two situations which give rise to the asymmetric reduction of a ketone. Hydrogen transfer from an optically active reducing agent to the carbonyl carbon of an inactive ketone is one possibility. Asymmetric reduction may also be produced by hydrogen transfer to a keto carbonyl adjacent to an asymmetric center. The latter type of reaction has been studied extensively by Cram and his coworkers. Inspection of the necessary conditions for this kind of asymmetric reduction reveals some similarity to the keto ester reductions described in Section II. 

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