Anti-lock-and-key

In 1993 Burk, Brown, and coworkers confirmed that DuPHOS complexes exhibit the same anti-lock-and-key mechanistic motif as seen for aryl phosphine ligated catalysts [41], In 1998 by Burk and coworkers reported an unexpected and interesting result [34], With substrates having R<, = aryl, selectivity of 99% e.e. for the S product resulted from (S,S)-Me-DuPHOS-Rh hydrogenations, but the R product was obtained with similarly high enantioselectivity when Ra = t-Bu or adamantyl. In other words, the simple change of an aryl substituent to a bulky alkyl completely reverses the sense of enantioselection. 

Our calculations reproduce the anti-lock-and-key behavior seen experimentally. Pro-S is 3.6 kcal/mol more stable than Pro-/ but the overall barrier along pathway A on the S manifold is 20.4 kcal/mol, over 4.4 kcal/mol greater than the overall barrier along pathway A on the R manifold. As is observed experimentally, our calculations predict the dominant product of (/ ,/ )-Me-DuPHOS-Rh hydrogenations to be the R enantiomer. Computed... 

Experimental studies by the groups of Halpern and Brown [69, 70] on the hydrogenation of prochiral alkenes by a chelating-diphosphine catalyst provided a detailed, and unexpected, picture of the overall mechanism of hydrogenation. The reaction of the catalyst with a prochiral alkene can produce two diastereomeric catalyst-alkene complexes. The most stable (and most abundant) diastereomeric complex is relatively unreactive, whereas the small amount of the complex in the less populated diasteromeric state gives the productive catalytic cycle. Landis has coined the phrase anti-lock-and-key motif to describe this mechanistic model. 

The computational study of the model system at QM level, followed by the ONIOM study on the real system, was able to answer some key questions about the asymmetric hydrogenation of alkenes. These theoretical investigations helped us to understand the anti-lock-and-key motif and the origin of the intriguing enantioselectivity upon changing the substituent of the al-kene from nitrile to f-Bu. 

Some have termed the kinetic preference for the less stable diastereomer—that is, the diastereomer characterized by a poorer substrate-metal fit than is the case with the more stable isomer—the anti-lock-and-key behavior of catalytic asymmetric hydrogenation. See also Footnote 10. 

Landis, C.R. Feldgus, S. A simple model for the porigin of enantioselection and the anti "lock-and-key" motif in asymmetric hydrogenation of enamides as catalyzed by chiral diphosphine complexes of Rh(I). Angew. Chem., Int. Ed. Engl. 2001. 39 (16), 2863-2866. 

Stereochemistry of Homogeneous Catalysts. Anti-Lock and Key Concept... 

Interestingly, the major product comes from the very rapid hydrogenation of the less stable diastereomer with H2. This feature that the least-stable intermediate is actually the most reactive has been called anti-lock and key behavior. The enantioselectivity of the reaction is affected by the competition between the rate of hydrogenation and the interconversion of the two diastereomers. 

We have illustrated that for a catalytic reaction in a zeolite to have a maximum rate, the adsorption free energy should be a maximum. Zeolites with medium-sized cavities are preferred over zeolites with small cavities because in the latter entropy loss dominates the gain in enthalpy. This compares with the anti-lock-and-key behavior of some enantiomeric catalytic systems discussed in the final section of Chapter 2. The catalytic systems that have an optimal misfit with their cavity perform the best, again demonstrating that the occupation is maximized while minimizing the entropy loss. 

The induced lock and key principle refers to a flexible catalyst lattice that adapts its shape to that of the substrate. The anti-lock and key principle refers to enantioselective catalytic systems where the state of most unfavorable binding yields the preferred product. The entropy difference here determines the selectivity. 

An important commercial application of these types of catalysts is in the production of L-dopa for the treatment of Parkinson s disease. The key to this application is the stereoselectivity shown by the phosphine chelate, (25,35)-bis(diphenylphosphino)butane, called chiraphos. In a benchmark study, Halpem and co-workers found that the Rh system is unusual in that the most stable olefin adduct does not lead to the major or desired product. This mechanistic pathway has been termed the anti-lock-and-key mechanism to contrast it with the lock-and-key mechanism often proposed for enzyme catalysis. In the latter, it is assumed that the best fit of substrate and enzyme will give the most effective catalysis. 

These calculations were able to reproduce the anti lock-and-key mechanism observed experimentally the most stable pro-5 intermediate displays the highest reaction barrier, while the pro-/ complex, higher in energy, has the lowest barrier to... 

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