Stereo-differentiating hydrogenation

Stereo-Differentiating Hydrogenation of (R)-4-Hydroxy-2-pentanone (6) to 2,4-Pentandiol (7) with TA-NaBr-MRNi"... 

Figure 4 Stereo-differentiating hydrogenation of methyl 2-methyl-3-oxobutanoate. (Selected data from Ref. 10).

Table 7 Stereo-differentiating hydrogenation of 1,3-diketones (1) over MNi catalysfSource Selected data from Refs. 26, 34.

Taking the above mentioned characteristics of the two modes into consideration, we introduced the concept of stereo-control in the enantio-differentiating hydrogenation of various functionalized prochiral ketones on TA-MNi based on the coexistence of 2P and IP on the site of the catalyst. That is the IP function coimteracts the 2P function when IP and 2P coexist, and the relative contribution of the two modes determine the stereochemistry of the product produced in excess and also relates qualitatively to the i factor. 

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. 

During the development of MRNi, in 1977 (61a, 61b) we proposed an hypothesis about the mechanism of hydrogenation on the surface of metal catalysts (61a, 61b). In 1971-1974 we proposed the name stereo-differentiation, which is the basic principle for the so-called asymmetric reactions (24, 32, 34, 38, 62, 63). These have been the working hypotheses for the development of MRNi. 

Ito, K., Harada, T., and Tai, A. (1980) The stereo-differentiating (asymmetric) hydrogenation of the C=0 double bond with a modified nickel catalyst, XXXV. A facile method for the preparation of optically pure -diols. Bull. Chem. Soc. Jpn. 53, 3367 - 3368. 

Simple bond dissociations. Cleavages of a single bond in an OE" ion can be stereo-differentiating if the ion contains n- or 7c-orbitals as control elements. For example, (M — H)" ions formed by a-cleavage loss of the bridgehead hydrogen atom from the trans-annulated isomer a are more abundant than those from the cis-isomer b (Ture ek and Hanus 1983). In 8.23(a), the non-bonding n-orbital at... 

Despite the fact that the reaction is performed by one of the most reactive reagents, it is not only very stereo- but also remarkably regioselective. Fluorine will differentiate, for example, between the three tertiary hydrogens in menthyl acetate (9. R = Ac) and substitute the one... 

Thus, the enantio-face differentiation of the substrate occurs in an adsorption step, which is followed by a rate determining hydrogenation step. This hypothesis, which is based on stereochemical and kinetic information, is the focus of the "Reaction Process Model" as illustrated in Figure 5. An important implication is that the activated complex of the rate-determining step need not be considered in order to explain or improve the stereo-control of the reaction. 

Optically purified hydrogenation products listed in Table 7 and 10 are promising compounds as a chiral synthetic block for the synthesis of various natural products as well as a chiral auxiliary for diastereo-differentiating reactions. Using available optically purified reaction products, we have carried out several application studies. Among them, two major works, in the field of bioactive natural products and stereo controlled synthetic organic chemistry, will briefly be mentioned. 

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