Asymmetric Hydrogenation of Prochiral Allylic Alcohols

Optimization of the enantioselective catalytic key steps calls for careful experimental investigation of many reaction parameters. Besides temperature, concentration of substrate, solvent effects, pressure, and conversion rate, a defined robustness of the process towards impurities, for example contained in reagents, as well as its sensitivity towards air (oxygen) or moisture at various temperatures are important aspects. In particular, the purity of prochiral substrates is of utmost importance for the success of asymmetric hydrogenation experiments. As a consequence, considerable attention had to be paid to even the smallest differences in the impurity profile of substrates, which may be due to different preparation and/or purification procedures at lab, pilot, or production scale. 

In view of efficient research and development activities within the limited time frames allocated to projects today, broad ligand and catalyst libraries are indispensable tools for rapid evaluation of the technical feasibility of the processes. For production purposes, short reaction times (full conversion in less than 10 hours) at high s/c ratios (preferably 50000) and high ee values have to be reached. A very high enantioselectivity (preferably 98% ee) is indeed essential, since the optical purity of (liquid) chiral isoprenoids cannot be improved in an economical manner, such as by crystallization. 

Another important aspect is the selection of the organometallic catalyst precursor responsible for generation of the active catalytic species. The suitable combination of metal complex and chiral ligand determines the efficiency of the process, 

---