Substrate-directive hydrogenation

Mediators can be nsed in certain cases when the enzyme does not interact with a substrate directly. Thus, in the presence of dehydrogenase inunobilized on carbon black, cathodic hydrogen evolution can be realized only when adding methylviolo-gen to the solution. The enzyme rednces methylviologen, while the reduced form of this mediator in turn reduces protons to gaseous hydrogen in the solution layer next to the electrode. 

The mechanism of the MPVO reactions has been investigated and questioned on several occasions, and a variety of direct hydrogen-transfer pathways have been suggested (see Scheme 20.4) [31-35]. Recently, racemization of D-labeled 1-phenylethanol with deuterated samarium(III) isopropoxide (17) proved that the MPVO reaction occurs via a direct hydrogen transfer from the a-position of the isopropoxide to the carbonyl carbon of the substrate (Scheme 20.7) [31]. 

In these reactions, the major diastereomer is formed by the addition of hydrogen syn to the hydroxyl group in the substrate. The cationic iridium catalyst [Ir(PCy3)(py)(nbd)]+ is very effective in hydroxy-directive hydrogenation of cyclic alcohols to afford high diastereoselectivity, even in the case of bishomoallyl alcohols (Table 21.4, entries 10-13) [5, 34, 35]. An intermediary dihydride species is not observed in the case of rhodium complexes, but iridium dihydride species are observed and the interaction of the hydroxyl unit of an unsaturated alcohol with iridium is detected spectrometrically through the presence of diastereotopic hydrides using NMR spectroscopy [21]. 

As described hitherto, diastereoselectivity is controlled by the stereogenic center present in the starting material (intramolecular chiral induction). If these chiral substrates are hydrogenated with a chiral catalyst, which exerts chiral induction intermolecularly, then the hydrogenation stereoselectivity will be controlled both by the substrate (substrate-controlled) and by the chiral catalyst (catalyst-controlled). On occasion, this will amplify the stereoselectivity, or suppress the selectivity, and is termed double stereo-differentiation or double asymmetric induction [68]. If the directions of substrate-control and catalyst-control are the same this is a matched pair, but if the directions of the two types of control are opposite then it is a mismatched pair. 

Bis-allylic oxidation of 23 and related cyclohexa-1,4-dienes provides a convenient and general preparation of cyclohexa-2,5-dien-l-ones (Scheme 7). These cross-conjugated die-nones are substrates for a variety of photochemical rearrangement and intramolecular cycloaddition reactions. Amide-directed hydrogenations of dienones 24a and 24b with the homogeneous iridium catalyst afford cyclohexanones 25a and 25b, containing three stereogenic centers on the six-... 

In spite of the success of asymmetric iridium catalysts for the direct hydrogenation of alkenes, there has been very limited research into the use of alternative hydrogen donors. Carreira and coworkers have reported an enantioselective reduction of nitroalkenes in water using formic acid and the iridium aqua complex 69 [66]. For example, the reduction of nitroalkene 70 led to the formation of the product 71 in good yield and enantioselectivity (Scheme 17). The use of other aryl substrates afforded similar levels of enantioselectivity. 

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