Chiral Catalysts

Chirality is a common phenomenon in nature. With the deepening of research on chiral drugs, chiral pesticides and chiral materials, the demand for optically pure chiral compounds has increased dramatically, which has greatly promoted the development of chiral synthetic chemistry. Asymmetric catalysis is currently the most effective strategy for chiral synthesis. Representative asymmetric catalytic systems include enzymes, metal complexes and small organic molecules, which are collectively referred to as three types of pillar-type asymmetric catalysts. Chiral catalysts are catalysts containing chiral C atoms, just like Figure 1, which play a pivotal role in some synthetic reactions.

Figure 1. Structure of terpenoid-derived chiral catalyst

Applications

Chiral catalysts contain chiral ligands and central metal atoms. Of course, some reactions are only catalyzed by chiral ligands without the need for metal atoms. It is the most effective way to obtain chiral substances. The central metal atom and chiral ligand of the chiral catalyst are two aspects of chiral catalysis, which are equally important. We can increase the selectivity of the asymmetric reaction by changing the type of metal and the type and structure of the chiral ligand. Commonly used central metal atoms are main group metals Li, Mg, Ba, Al, etc. to transition metals Ti, Rh, Ru, Fe, Zn, Cu, Ni, Pd, etc.

After long-term research and practice, organic reactions have been found for asymmetric catalysis of different metals. For example, the chiral catalysts of metals Rh and Ru are suitable for asymmetric hydrogenation, and the chiral Ti complexes are suitable for catalyzing the Sharpless epoxidation, metal Al is suitable for catalyzing asymmetric D-A reaction, metal Pd is suitable for catalyzing allyl alkylation, the chiral Os catalyst is used for diol dihydroxylation, and chiral Cu catalyst is suitable for cyclopropane reaction, etc.

Since the ligand has a great influence on the chiral catalyst, the following are the precautions for chiral ligand design:

1. The chiral center may be close to the reaction center, but it may also allow 2 to 3 keys between the reaction center and the chiral center. This may sometimes convey chiral information, such as remote mismatch, etc.

2. A chiral ligand can have a larger group to reduce the degree of freedom of the transition state intermediate without hindering the reaction, or with a C2 axis of symmetry, which may result in a large difference in free energy between the two transition states, or reduce a possible reaction pathway.

3. For bidentate ligands, it is preferred to have a ring structure or a fragrance base.

4. When selecting the coordination atom and substituent of the chiral ligand, it is necessary to consider the coupling with the corresponding metal atom, and can generate secondary effects with the substituent of the reaction substrate, such as hydrogen bonding and electrostatic polarity, especially hydrogen bond.

Sources:

• Pure natural products as chiral catalysts: The use of pure natural products without any modification as a chiral catalyst is not very much, and the enantioselective selectivity of the catalytic organic reactions is generally not so good. Strychine and sparteine are currently more commonly used. You can see the structures of sparteine in Figure 2.

Figure 2. Structure of sparteine

• Artificially modified products as chiral catalysts: Such catalysts mainly refer to catalysts derived from natural substances such as alkaloids, amino acids, carboxylic acids, chiral carbohydrates, and terpenoids.
• Synthetic chiral catalysts: In the synthetic chiral ligands, the chiral lining and amino alcohol compounds are the main components, as shown in Figure 3 and Figure 4 below.

Figure 3. Structure of BINOL.

Figure 4. Structure of BINAP.

References

1. Hembury, G. (2008).Chirality-Sensing Supramolecular Systems.Chem. Rev. 108 (1): 1-73.
2. YaoLi. (2018).Rational Design of Chiral Catalysts Based on Experimental Data and Reaction Mechanism. Chin. J. Org. Chem.38:2363-2376.
3. Masashi Yamakawa. (2001). Metal-Ligand Bifunctional Catalysis: A Nonclassical Mechanism for Asymmetric Hydrogen Transfer between Alcohols and Carbonyl Compounds.J. Org. Chem. 66(24).