Question

The chiral catalyst \((R)\)-BINAP-Ru is used to hydrogenate alkenes to give alkanes (Section 6.7C). The products are produced with high enantiomeric excess. An example is the formation of \((S)\)-naproxen, a pain reliever.

Short answer

Question: Describe the process of synthesizing (S)-naproxen with a high enantiomeric excess using the chiral catalyst (R)-BINAP-Ru. Answer: To synthesize (S)-naproxen with high enantiomeric excess, the hydrogenation of the alkene precursor occurs using the chiral catalyst (R)-BINAP-Ru. This catalyst selectively promotes the formation of the desired (S)-naproxen enantiomer while minimizing the formation of the undesired (R)-enantiomer. This results in a product with a high enantiomeric excess, which is important for achieving the desired biological activity.

Step-by-step solution

Hydrogenation of alkenes

Hydrogenation is the process through which alkenes (unsaturated hydrocarbons with a carbon-carbon double bond) are converted into alkanes (saturated hydrocarbons without double bonds) by adding hydrogen to the carbon-carbon double bond.The process involves a catalyst, which is typically a metal such as Palladium (Pd) or Platinum (Pt). In this case, the catalyst is a chiral Ruthenium compound, \((R)\)-BINAP-Ru.

Chiral catalyst \((R)\)-BINAP-Ru

A chiral catalyst is a compound that selectively promotes the formation of one enantiomer of the product over the other, leading to enantiomerically enriched products. \((R)\)-BINAP-Ru is a metal complex derived from BINAP (2,2'-bis(diphenylphosphino)-1,1'-binaphthyl) and a Ruthenium center. The \((R)\)-BINAP ligand is chiral, providing the necessary stereochemistry to selectively hydrogenate alkenes in an enantiospecific fashion.

Enantiomeric excess

An enantiomeric excess (ee) is a measure of the degree of enrichment of one enantiomer by the catalyst. A high enantiomeric excess indicates that the catalyst is promoting the formation of one enantiomer over the other more efficiently. This is particularly important in the synthesis of compounds with stereocenters, as the biological activity often depends on the stereochemistry. Therefore, producing products with high enantiomeric excess is crucial for pharmaceutical applications.

Formation of \((S)\)-naproxen

Naproxen is a non-steroidal anti-inflammatory drug (NSAID) that is marketed in both racemic and enantiomerically enriched forms. The \((S)\)-forms of the drug exhibit higher biological activity. To synthesize \((S)\)-naproxen from an alkene precursor, the hydrogenation reaction must occur in a manner that selectively produces the desired \((S)\)-enantiomer and minimizes the formation of the undesired \((R)\)-enantiomer. This is achieved by using the chiral catalyst \((R)\)-BINAP-Ru in the hydrogenation process. The catalyst selectively promotes the formation of the \((S)\)-naproxen enantiomer, giving a product with a high enantiomeric excess. In conclusion, the hydrogenation of alkenes to form alkanes with high enantiomeric excess is possible using the chiral catalyst \((R)\)-BINAP-Ru. This is particularly important for the synthesis of pharmaceutically active compounds such as \((S)\)-naproxen, where the stereochemistry plays a crucial role in the biological activity of the molecule.