Congratulations to Kavnen Tseke, PhD Researcher with the PMBRC, on the publication of a recent article in the prestigious European Journal of Organic Chemistry (EurJOC).
Link to full article:
A Continuous-Flow Route to Enantioenriched 3-Substituted-3-Hydroxyoxindoles: Organocatalytic Aldol Reactions of Isatin with Acetone.
An efficient L-leucinol catalysed asymmetric synthesis of 3-substitued-3-hydroxyoxindoles was for the first time completed under continuous flow, providing a safer route for accelerating the reaction at higher temperatures without adversely affecting enantioselectivity. Initial batch solvent screening of the isatin-acetone aldol reaction revealed neat acetone as the media best suited in flow as it dissolved isatin and afforded (S)-enantiomer of the adduct in 84% ee. Solvents with Kamlet-Taft basicity (β)>0.6 and proticity (α)~0 had a higher solubility of isatin but poor reaction performance while solvents with β<0.2 and α<0.6 performed excellently in the reaction albeit with poor isatin solubility. The addition of 10 equivalents of water improved the neat reaction to afford 94% yield in 93% ee at 20°C after 48 hrs. When transferred to continuous flow, complete conversion was observed in 12 hrs residence time at 40°C without loss in enantioselectivity. Further substrate studies in flow were undertaken with a 4-fold dilution and a 60°C reaction temperature required for some derivatives. Excellent yields and enantioselectivities were obtained in most cases.