Asymmetric hydrogenation energetics

An asymmetric hydrogen bond is common even where a proton coordinates two equivalent anions. The rc-bond repulsive forces between two coordinated anions tend to prohibit a close X-H-X separation, so competition between the two equivalent anions for the shorter X-H bond may set up a double-well potential for the equilibrium proton position between the two coordinated anions. With oxide anions, an O-H-O separation greater than 2.4 A sets up a double-well potential and creates an asymmetric hydrogen bond, which we represent as O-H O. Although displacement toward one anion may be energetically equivalent to a displacement toward the other, one well is made deeper than the other by an amount AH, as a result of the motion of the proton from the centre of the bond. 

Much like the enol systems discussed in Sect. 6.1, enamines are predictably difficult substrates for most iridium asymmetric hydrogenation catalysts. Both substrate and product contain basic functionahties which may act as inhibitors to the catalyst. Extended aromatic enamines such as indoles may be even more difficult substrates for asymmetric hydrogenation with an additional energetic barrier to overcome. Initial reports by Andersson indicated a very difficult reaction indeed (Table 14) [75]. Higher enantioselectivities were later reported by Baeza and Pfaltz (Table 14) [76]. 

Figure 4.10. Energetics of asymmetric hydrogenation by Rhodium DIPAMP complexes.

Thus, the delicate process of enantioselection in the asymmetric hydrogenation of p-dehydroamino acids can be roughly described as being determined by the mode of coordination of the double bond of the substrate in octahedral Rh(III) intermediates. The enantioselectivity could be correctly predicted for all studied cases if only the dihyride pathway is considered. The order of enantioselection in each particular case can be affected either by the entropic effect on the activation barrier for the double bond coordination specific for each substrate or by the interference of other catalytic pathways, for example, the unsaturated route, which has been computed to be more energetically demanding and significantly less stereoselective in the case of (Z)-P-dehydroamino acids. 

Figure 10.5. The protein environment can influence hydrogenic wavefunction overlap via asymmetrically coupled modes which bring hydrogenic wavefunctions into energetic coincidence [vertical perturbation, shown on left-hand side of figure]. These modes give rise to terms analogous to the Marcus theory of electron transfer [122]. Additionally,...

---