Title : Silica-immobilized bifunctional L-prolinol organocatalysts: Stereoselective Michael addition in heterogeneous environment
Stereoselective Michael additions represent the staple reactions in the field of organic synthesis. The stereoselectivity of the reactions is usually mediated by bifunctional catalysts, which activate both the electrophile and nucleophile at the same time. One of the many challenges in the field is to develop a suitable heterogeneous catalytic system, which provides an easy way of regeneration of the catalyst by standard filtration.
Herein we present a series of bifunctional L-prolinol based organocatalysts (Ia-c), which have also been immobilized via click-reaction to azidopropyl-modified silica solid phase yielding heterogeneous catalysts (IIa-c; Scheme 1a). The synthesis as well as the catalytic properties of both the homogeneous (Ia-c) and the heterogeneous (IIa-c) catalysts in a selected model Michael addition of cyclohexanone and β-nitrostyrene (Scheme 1b) will be discussed.
The experiments showed a very high impact of the solvent polarity on both yield and stereoselectivity. The less polar solvents used (hexane, toluene) delivered the highest conversion and stereoselectivity, whereas the polar solvents (dichloromethane, methanol) were significantly less effective. Nevertheless, the best results were achieved in neat cyclohexanone (up to 93% ee; up to 98% de) .
Furthermore, the catalysts were packed in-house into stainless steel columns (150x4 mm) and tested in a continuous flow reaction setup, which does not require the filtration step during the catalyst regeneration cycle and thus enables a quick and easy regeneration by simple washing.
A general preparation strategy of silica-based heterogeneous organocatalysts, their catalytic activity, properties, easy tunability and their potential for scale-up applications will be discussed.