Towards the enantioselective synthesis of alcohols by homogeneous supported tandem catalysis

Enantio-enriched alcohols present a large range of applications in the pharmaceutical industry. A current synthesis strategy for their production is based on two subsequent reactions: the hydration of alkynes followed by the asymmetric reduction of the formed ketones. Since chemical production costs have always been an obstacle for industrial development of organometallic catalytic systems, a current trend consist in facilitating work-up procedures, either via catalyst recycling or tandem catalysis. Considering all these parameters we targeted the development of a supported tandem catalytic system for the production of enantio-enriched secondary alcohols. We decided to work with carbon nanotubes as heterogeneous support due to their intrinsic resistance properties as well as the well-described functionalization strategies available. The first part of this project concerned the phenylacetylene hydration. We achieved gold NP deposition as well as cationic gold impregnation on CNTs. Both catalysts presented a good reactivity for the hydration of alkynes but systematically generated the anti-Markovnikov product of the reaction: the phenylacetaldehyde. The second catalyst development was based on cobalt complexes. We synthesized a salen ligand compatible with downstream coupling on CNTs. Cobalt-mediated alkyne hydration presented total conversion of phenylacetylene into acetophenone in mild conditions. In addition, we developed two grafting strategies for our complex, based either on Sonogashira or Suzuki and highlighted the activity of both heterogeneous catalysts. The second part of this project concerned the asymmetric reduction of acetophenone. We developed and synthesized a chiral diamine ligand bearing a pyrene moiety for π-π immobilization on CNTs. Immobilization efficiency – with both ruthenium and iridium complexes- was close to 33%. Catalytic tests were performed with iridium and highlighted good activity in homogenous phase. Additionally, Ir-based heterogeneous catalysts showed a significantly better activity that their homogeneous equivalents. Following the successful development of both heterogeneous catalysts, we intended to combine the reactions to develop a tandem catalytic system. However, preliminary results rapidly highlighted that both systems were hardly compatible and further researches will be required.