Hydrogenation carbonyl-selective

Reduction of unsaturated aldehydes seems more influenced by the catalyst than is that of unsaturated ketones, probably because of the less hindered nature of the aldehydic function. A variety of special catalysts, such as unsupported (96), or supported (SJ) platinum-iron-zinc, plalinum-nickel-iron (47), platinum-cobalt (90), nickel-cobalt-iron (42-44), osmium (<55), rhenium heptoxide (74), or iridium-on-carbon (49), have been developed for selective hydrogenation of the carbonyl group in unsaturated aldehydes. None of these catalysts appears to reduce an a,/3-unsaturated ketonic carbonyl selectively. 

Isolated double and triple bonds are reduced readily, whereas conjugated alkenes and aromatic systems are difficult to hydrogenate. Carbonyl double bonds react only very slowly, if at all, so it is possible to achieve selective reduction of C=C double bonds in the presence of aromatic and carbonyl functions. 

It must be emphasized that the above considerations were made in the absence of reaction. Interfacial mass transfer followed by reaction requires further consideration. The Hatta regimes classify transfer-reaction situations into infinitely slow transport compared to reaction (Hatta category A) to infinitely fast transport compared to reaction (Hatta category H) [42]. In the first case all reaction occurs at the interface and in the second all reaction occurs in the bulk fluid. Homogenous catalytic hydrogenations, carbonylations etc. require consideration of this issue. An extreme example of the severity of mass transport effects on reactivity and selectivity in hydroformylation has been provided by Chaudari [43]. Further general discussions for homogeneous catalysis can be found elsewhere [39[. 

The support effect in terms of selectivity can be observed in Table 3. The results show that the axial-equatorial carvomenthol is the only product when the support is magnesia. Rh/MgO catalysts results to be highly stereoespecific for the hydrogen carbonyl addition. 

Enantioselective hydrogenation of unsaturated ketones giving chiral unsaturated alcohols is achievable by only limited catalysts. With most existing heterogeneous and homogeneous catalysts, saturation occurs at C=C bonds preferentially over C=0 [270]. Thus development of carbonyl-selective and enantioselective hydrogenation is highly desirable. 

Asymmetric hydrogenation of simple 2-cyclohexenone is still difficult. A catalyst system prepared in situ from [Ir(OCH3)(cod)]2 and DIOP shows carbonyl-selectivity as high as 95% at 65% conversion, but with a poor enantioselectivity (Scheme 1.69) [274],... 

Carbonyl-selective asymmetric hydrogenation of 2-cyclohexenone - a simple cyclic conjugated enone - is stdl difficult, but some substituted 2-cydohexenones such as 2,4,4-trimethyl-2-cyclohexenone, (R)-carvone, a chiral dienone, and (R)-pule-gone, an s-cis chiral enone have been used successfully [66, 68, 81b, 107]. 

Alkenes are converted to epoxides by oxidation with peroxy acids, and thereby they are protected with regard to certain chemical transformations. Alkaline hydrogen peroxide selectively attacks enone double bonds in the presence of other alkenes. The epoxides can be transformed back to alkenes by reduction-dehydration sequences or using triphenylphosphine, chromous salts, zinc, or sodium iodide and acetic acid. A more advantageous and fairly general method consists, however, of the treatment of epoxides with dimethyl diazomalonate in the presence of catalytic amounts of binuclear rhodium(II) car-boxylate salts. This deoxygenation proceeds under neutral conditions and without isomerization or cy-clopropanation of the liberated alkene (Scheme 97). Furthermore, epoxides can be converted to alkenes with the aid of various metal carbonyl complexes. Thus, they may be nucleophilically opened with... 

Carbonyl-selective asymmetric hydrogenation of simple 2-cyclohexenone is still difficult. The optical yield obtained with [Ir(OCH3)(cod)]2-DIOP is only 25%, while the carbonyl-selectivity is 95% at 65% conversion (Scheme 23) [80]. Hydrogenation of 2,4,4-trimethyl-2-cyclohexenone with a Ru(II)-TolBINAP-4-KOH catalyst system under 8 atm of hydrogen at 0 °C gives 2,4,4-trimethyl-2-cy-clohexenol quantitatively in 96% ee [81, 82]. Notably, the combination of (R)-TolBINAP and (S,S)-4 matched well to give the S alcohol with a high ee. The chiral allylic alcohol is the key intermediate in the synthesis of carotenoid-derived odorants and other bioactive compounds [83]. 

Carbonyl hydrogenation is generally less facile than olefin hydrogenation, making selective hydrogenation of a, -unsaturated aldehydes to the allyl alcohol a special challenge. Substitution of the carbon atom attached to the carbonyl (i. e. from the aldehyde to the ketone), substantially increases the steric hindrance to carbonyl adsorption, hence the lack of reports in the literature of selective unsaturated ke-... 

Figure 6.27 Experimental heats of hydrogenation for selected carbonyl compounds and alkenes. ...

Such dynamic kinetic resolutions can also be conducted on cyclic jS-keto esters. Two examples are shown in Equations 15.59 and 15.60. Such cyclic substrates contain a stereocenter at the carbon between the two carbonyl groups. Again, a dynamic kinetic resolution of these substrates by hydrogenation occurs selectively to form predominantly a single stereoisomer. This reaction occurs to form a 99 1 ratio of diaste-reomers and 93% enantioselectivity of the major diastereomer in the presence of a ruthenium-BINAP catalyst. The positions of the keto and ester functionalities can also be reversed. Reduction of the cyclic p-keto ester in Equation 15.60 generates, in this case, the cis diastereomer with high diastereoselectivity and enantioselectivity. ... 

Thus the catalyst has to favor first of all CO insertion over pure hydrogenation. This selectivity issue is mainly addressed by the choice of central transition metal for the hydroformylation catalysis. Obviously, all metals active in hydroformylation show a pronounced tendency to form metal carbonyl complexes. However, only Rh and Co complexes show sufficiently high hydroformylation activity for commercial applications, with rhodium being 1000-10000-fold more active, but also about 1000-fold more expensive, than cobalt (Moulijn, Makkee, and van Diepen, 2001). 

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