An investigation of chiral diamides as organocatalysts in asymmetric aldol reaction

Abstract

Seven novel proline and 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQA) based diamides were synthesized successfully by simple amidation reactions and characterized by their spectral data. Their catalytic activities in asymmetric aldol reaction were performed by the reactions of aliphatic ketones and various aromatic aldehydes. Especially, (S)-N-((S)-1-(morpholinoamino)-1-oxo-3-phenylpropan-2-yl)pyrrolidine-2-carboxamide (9e) showed good catalytic activities in water at room temperature in the presence of benzoic acid cocatalyst. The enantioselectivities were upto 89.6%, the diastereomeric ratios were upto 92/8, and yields were upto 97.3%. This catalyst showed its best catalytic activities in water; this is also an important contribution to green chemistry requirements.

Water-enabling strategies for asymmetric catalysis

“…In 2021-2022, Yolacan and colleagues reported that chiral Pro-Phe-derived dipeptide catalysts with an aromatic acid as the co-catalyst exhibited higher catalytic activity in water than in other solvents when catalyzing the asymmetric aldol reactions of aliphatic ketones with aromatic aldehydes (Scheme 2a). 8,9 In 2021, Makatini and coworkers reported a solid-phase peptide-promoted aldol reaction between ketones and aldehydes (Scheme 2b). 10 Addition of a small amount of water was beneficial for yield and stereoselectivity.…”