Enantioselective Conversion of Achiral Diketones and Triketones for Shortened Bioactive Molecule Synthesis
Final Report Abstract
This research period evolved from the stated Work Packages into the identification and development of a new capability for ‘in water’ reaction conditions. By example, model substrates based on 4-substituted cyclohexanones, containing various β-diketone moieties, were reacted with aldehydes. Under amino acidic catalysis using organic solvents (EtOH or DMSO), the expected Knoevenagel product was formed. When small or large quantities of water were added to those reactions, homogenous reactions resulted, but the aldol-to-Knoevenagel chemoselectivity never raised above a 1.0:1.1 ratio. By contrast, heterogeneous in water reaction conditions gave a biphasic mixture and exclusively provided the aldol product. Preliminary mechanistic experimentation points to a rapid hydrolysis capability for in water (heterogeneous) reaction conditions that had not been previously taken exploited. In brief, we have expanded the known capabilities for in water reactions and in doing so were able to demonstrate the first aldol over Knoevenagel reaction selectivity.
Publications
-
Harnessing Additional Capability from in Water Reaction Conditions: Aldol versus Knoevenagel Chemoselectivity, Advanced Synthesis & Catalysis Volume 363, Issue 14, July 20, 2021, Pages 3539-3545
Nugent, Thomas C.; Goswami, Falguni; Debnath, Samarpita; Hussain, Ishtiaq; Ali El Damrany Hussein, Hussein; Karn, Alka & Nakka, Srinuvasu
