9.4 Industrial Applications of Asymmetric Reduction of C=C Bonds

Finding an economic process for an asymmetric hydrogenation relies on extensive screening. In this chapter we show that there is a lot more to this than just screening metal precursors and ligands. The choice of starting material can make a huge difference. In addition, the purity of the starting materials can have a strong effect on rate and enantioselectivity. Also, the choice of the solvent is of crucial importance; it almost always pays to screen a range of solvents at an early stage. Temperature and pressure can have a huge effect on the reaction rate but an increase often affects the enantioselectivity in a negative way. In the end a satisfactory enantiomeric excess ( ee ) can usually be achieved, however, increasing the rate in such a way that an economic substrate catalyst ratio can be used can be more troublesome. Often, the desired rate can be achieved by a combination of factors. Details are described of the asymmetric hydrogenation step in the industrial processes for citronellol, (+)-c is- methyl dihydrojasmonate, l -menthol, Synthon A (a precursor for Aliskiren™), Laropiprant, Candoxatril, Tipranavir, and Rozerem.