8.15:
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
Catalytic hydrogenation of an alkene is the reduction of the C=C bond using molecular hydrogen to give an alkane in the presence of a transition-metal catalyst.
The catalyst used for hydrogenation can be heterogeneous, that is, finely divided metal over charcoal, or homogeneous, like Wilkinson's catalyst, giving a syn addition product.
Since the reaction results in a new chiral center in the product, a pair of enantiomeric products is anticipated.
Now the question arises — is it possible to produce a single enantiomeric product instead of a pair of enantiomers?
For an alkene of this type, an enantiomeric excess of one of the products can be achieved through hydrogenation, using a chiral homogeneous catalyst.
This is called asymmetric hydrogenation. In this reaction, the chiral catalyst significantly reduces the activation energy for the formation of one enantiomer over the other.
The catalysts generally used are ruthenium and rhodium complexes coordinated to a chiral phosphine ligand like "BINAP".
Although the ligand itself has no chiral centers, its chirality arises from the restricted rotation of the two rings about the single bond.
The chelating diphosphine provides a chiral catalyst with the metal anchored to the two phosphorus atoms in a chiral atmosphere.
The catalyst has several industrial applications; for instance, it catalyzes the asymmetric synthesis of the anti-inflammatory (S)-naproxen with more than 98% ee.
Another application is towards the asymmetric hydrogenation of geraniol, a natural product isolated from rose oil.
Interestingly, although geraniol contains two double bonds, the one nearer to the –OH group undergoes reduction.
Therefore, for substrates undergoing asymmetric hydrogenation, a neighboring functional group close to a double bond is essential for coordinating to the metal catalyst.
8.15:
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
Catalytic hydrogenation of alkenes is a transition-metal catalyzed reduction of the double bond using molecular hydrogen to give alkanes. The mode of hydrogen addition follows syn stereochemistry.
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an asymmetric hydrogenation process using chiral homogeneous catalysts. The chiral catalysts are designed such that the metal coordinates to a chiral ligand. The most frequently used chiral ligand is BINAP [(2,2'-bis(diphenylphosphino)-1,1'-binaphthyl] — a chelating diphosphine. The metal coordinates to the two phosphorus atoms of BINAP, creating a chiral environment for itself. Such chiral catalysts have tremendous applications in pharmaceutical industries, such as the asymmetric synthesis of (S)-naproxen, an anti-inflammatory drug molecule, and the synthesis of L-dopa, a drug used to treat patients with Parkinson's disease.
Asymmetric hydrogenation is specific to the type of double bond undergoing reduction. The presence of a functional group directly adjacent to the target double bond is essential for the hydrogenation process as it aids with effective coordination of the metal.