Dynamic crystallization processes of P-chiral phosphine oxides
|PhD ceremony:||Mr F.A. (Felix) Kortmann|
|When:||October 10, 2014|
|Supervisor:||prof. dr. ir. A.J. (Adriaan J) Minnaard|
|Where:||Academy building RUG|
|Faculty:||Science and Engineering|
Asymmetric catalysis has become an indispensable concept for modern organic chemistry. Especially for pharmaceutical research and industry, with its high demand for enantiopure compounds it is extremely valuable. A huge variety of transformations, including enantioselective reductions and oxidations, nucleophilic direct additions, conjugate additions, aldol reactions, allylic alkylations, Diels–Alder reactions, 1,3-dipolar additions, enyne cyclizations, cyclopropanation, and olefin-metathesis is well established and readily used on lab- and industrial-scale.
Chiral (often phosphine/phosphorus-based) ligands are the key players in these transformations, underpinning their great importance not only for fundamental research but also (indirectly) for daily life. Enantiopure, P-chiral phosphine oxides are important precursors for phosphine ligands as well as potential ligands in asymmetric catalysis themselves. Their synthesis still poses a considerable challenge and the development of reliable, scalable and affordable routes is an important research topic.
This thesis focusses on innovative, crystallization-based routes for the synthesis of enantiopure P-chiral secondary and tertiary phosphine oxides. These dynamic crystallization processes and here in particular crystallization induced asymmetric transformations (CIAT) bear the big advantage, that they can overcome the intrinsic 50% yield-limitation of classical resolutions. The unwanted enantiomer is racemized in situ, thus in theory compounds can be obtained as a single enantiomer in 100% yield.