Substrate-controlled hydrogenation

The iridium catalyst [lr(COD)py(PCy )PFA] is utilized in substrate-controlled hydrogenations of allylic alcohols of the type 34, 36, and 38.25 The catalyst coordinates with the hydroxy group in the molecule, so hydrogenation occurs on ) from one side. 

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. 

In the hydrogenation of diketones by Ru-binap-type catalysts, the degree of anti-selectivity is different between a-diketones and / -diketones [Eqs (13) and (14)]. A variety of /1-diketones are reduced by Ru-atropisomeric diphosphine catalysts to indicate admirable anti-selectivity, and the enantiopurity of the obtained anti-diol is almost 100% (Table 21.17) [105, 106, 110-112]. In this two-step consecutive hydrogenation of diketones, the overall stereochemical outcome is determined by both the efficiency of the chirality transfer by the catalyst (catalyst-control) and the structure of the initially formed hydroxyketones having a stereogenic center (substrate-control). The hydrogenation of monohydrogenated product ((R)-hydroxy ketone) with the antipode catalyst ((S)-binap catalyst) (mis-... 

Burgess and coworkers investigated the hydrogenation of the conjugated diene 87 (Scheme 30.1) [48]. Kinetic studies showed that the reaction occurred mostly stepwise via 2,3-diphenyl-l-butene, while only a small part of the diene was converted directly to 2,3-diphenylbutane, without dissociation of the catalyst from the intermediate mono-alkene. The first hydrogenation step was found to proceed with low enantioselectivity, whereas the second step was characterized by strong catalyst and strong substrate control. 

Hydrogenation of diacetyl (5) catalyzed by (S)-l-Ru gives a 74 26 mixture of meso-6 and S,S-6. Evidently in this reduction catalyst control favoring formation of meso-diols dominates over substrate control favoring formation of / or d-diols. 

Fig. 7 Diastereoselective hydrogenation based on catalyst and substrate control...

When racemic methyl a-(l-hydroxyethyl)aciylate is hydrogenated by using the (S)-BINAP-Ru catalyst, the R substrate is depleted more easily than the S. At 76% conversion, the unreacted S enantiomer is obtained in greater than 99% ee, as well as a 49 1 mixture of the threo (2R,3R) and the erythro saturated products. Hydrogenation of the S substrate with either antipodal Ru catalyst results in 2S,3S hydroxy ester with equally high threo selection (>23 1). These data indicate operation of overwhelming substrate control in this particular reaction. 

The prototropic equilibrium constant (pRa) for the equilibrium between 0 and HO radicals is 4.7. Therefore at physiological pH, the superoxide radicals exist predominantly in the form of O radicals. HO radicals are more reactive than Oj radicals, and react with substrates by hydrogen abstraction or by addition to the double bonds. 0 radicals do not exhibit these reactions but participate in a number of redox reactions with metal ions and substrates like quinone, ascorbate, etc. The rate constants for these reactions are considerably lower than diffusion-controlled limits (10 to 10 s ). Oj ... 

In the following epoxidation step, m /a-chlorobenzoic acid (w-CPBA) has the choice to attack the 10,11-double bond or the 13,14-double bond. Because a hydrogen bond between the alcohol at C-9 and the peracid stabilizes the transition state 80, only the 10,11-double bond is epoxidized. In addition, this hydrogen bond also directs the attack to come from the same side as the alcohol and thus leads to a high substrate-controlled stereoselectivity. 

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