PROCURADURÍA GENERAL DE LA REPUBLICA

The French physicist Francois Arago discovered the power of rotatory polarisation exhibited by quartz back in 1811. He passed a polarised light beam through a quartz crystal and found the plane of the light was rotated.159 Then in 1835, Jean-Baptiste Biot also observed a similar phenomenon by replacing the quartz crystal with sugar solutions.160 This unusual observation could not be explained until 1848 when the difference between the tartaric acid crystals

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gained from wine production and those obtained via chemical synthesis was noted by Louis Pasteur.161 According to him, only the crystals obtained from chemical synthesis could rotate polarised light whereas those derived from wine production could not. Ingeniously, using his own eyes and a pair of tweezers, he managed to separate out two different types of ammonium sodium tartrate crystals into two piles. He noted that the crystals collected in one pile were mirror images of those in the other. Save for the visual differences of the crystals noted, almost all other physical properties (density, boiling point, solubility, hardness, etc.) were the same. Upon re-dissolving each set of crystals to form two ostensibly „identical‟ solutions, Pasteur discovered that one solution rotated the plane of polarised light in a clockwise way (known as dextrorotatory), while the other rotated the light in an anti- clockwise fashion (known as levorotatory). This property was called optical activity. The commercially sourced form of tartaric acid did not rotate polarised light in this way since both types of left- and right-handed crystal were present with equal amounts. The „asymmetry‟ between the two forms described by Pasteur was later termed „chirality‟ by Lord Kelvin in 1893. Based on these observations, van‟t Hoff managed to rationalise the basis of the chirality in organic molecules by assuming a tetrahedral arrangements of different atoms or groups around a central carbon atom.162 These discoveries relating to the subject of molecular and structural shape were later to become one of the most important topics in modern science.163 In this context, the present study will investigate the adsorption of molecules at solid surfaces in order to clarify the mechanism by which chiral auxiliary molecules steer the chiral outcome of prochiral alpha-ketoester hydrogenation in heterogeneous enantioselective catalysis.

Figure 1.9 Examples of chiral objects: (a) hands and (b) an sp3 hybridised carbon atom bonded to four different constituents.

Like a hand, an object which is chiral is non-superimposable on its mirror image (Figure 1.9). In molecular terms, such objects are usually composed of a series of stereoisomers

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called optical isomers (also enantiomers), each being a mirror image of the other. A molecule with the central carbon atom bonded to four different atoms or groups is therefore considered chiral. The atoms or groups bonded to the centre carbon are assigned a priority according to their mass and labelled 1-4 in descending order by using the Cahn-Ingold-Prelog system.164 Hence, enantiomers are named and labelled in this way. As shown in Figure 1.10, the enantiomer is viewed with the fourth atom/group with the lowest mass pointing away. If groups 1-3 in preference run in a clockwise way, the enantiomer will be noted with the prefix

R- (rectus) orS- (sinister) if 1-3 groups run anti-clockwise.

Figure 1.10 Enantiomers being described using the Cahn-Ingold-Prelog system of nomenclature.

Non-superimposable stereoisomers usually containing more than one stereocentre are termed

diastereoisomers. They are not mirror images of one another. Compounds containing two or

more stereocentres but in themselves are not chiral are termed meso-compounds, which in this case are superimposable on their mirror images (Figure 1.11).165

31 HOOC (R) HO H (S) OH H COOH HOOC (S) HO H (R) OH H COOH

2R,3S mesotartaric acid

2S,3R mesotartaric acid

HOOC (R) HO H (R) OH H COOH HOOC (S) HO H (S) OH H COOH

X

X

X

dextrotartaric acid

levotartaric acid

Figure 1.11 The meso-compounds are equivalent as they are superimposable on each other. Dextrotartaric acid is the enantiomer of levotartaric acid. The meso-compounds are diastereoisomers of dextro- and levotartaric acid. Reprinted from reference 165.

Since enantiomers possess this specific feature, their interaction with other chiral molecules or light has become an important area of research. Manufacturing pure enantiomeric compounds that contain exclusively only one type of handedness is the primary target in industry since such centres are crucial to all aspects of biochemistry with applications in fine chemicals including fragrances166, pharmaceuticals167, flavours168, and agrochemicals169. A mixture of equal amounts of two enantiomers is called a racemate. If one enantiomer is in excess, the excess can be quantified as a percentage of the total mixture. The so-called enantiomeric excess (ee) is quantified in the following equation:

(Eq. 1.10)

where [R] is the concentration of the R-enantiomer and [S] the concentration of the S- enantiomer. The numerator will be [S] – [R] if calculating the S-enantiomer percentage.

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It is often expensive to produce enantiomerically pure substances on a large scale. However, for a small quantity of racemate, the enantiomers can be separated by chiral chromatography.170 Also, using an enantioselective reaction can produce two chemically different diastereoisomers. Since each diastereoisomer will be chemically and physically distinct, they may be separated using classical methods of separation such as fractional distillation.171 When each separated diastereoisomer is subsequently treated chemically to regenerate the enantiomer, the resulting mixture will contain only a single enantiomer which may be further separated by standard means. Another method of separation of a racemic mixture into its individual enantiomers would be a kinetic resolution whereby a chemical such as an enzyme reacts preferentially with one of the enantiomers.172In this way, the racemate becomes enriched in a single enantiomer although of course, ultimately 50% of the initial sample will be destroyed in the process!

Since it is not easy to separate enantiomers, more efficient synthetic methods were developed to directly produce a single pure enantiomer.173 Enantioselective catalysis is applied to target the industrial problems of manufacturing enantiopure chemicals. A Nobel prize was awarded to Knowles, Noyori and Sharpless in 2001 for their use of homogeneous catalysts in enantioselective compounds production.174 However, three major difficulties were raised due to the usage of homogeneous catalysts if the enantiopurity needed to reach ≥99% ee. It includes the separation of both catalyst and product from the reaction mixture, limited chance of catalyst re-use, and high sensitivity to normal ambient conditions (such as with oxygen/water vapour being present). Many of these problems could be overcome if an enantioselective heterogeneous catalysts could be designed for similar purposes. This is because, simple filtration may remove the solid catalyst from the reaction mixture and regeneration by controlled heating in an oxygen or hydrogen ambient may often restore optimal catalytic behaviour.1