Highly asymmetric aldol reaction of isatins and ketones catalyzed by chiral bifunctional primary-amine organocatalyst on water

Abstract

An efficient asymmetric aldol reaction between isatins and ketones on water has been reported, which afforded a series of enantioenriched 3-hydroxy-2-oxindoles in excellent yields and stereoselectivities under mild conditions.

Aldol Insights: The Route to Chiral Synthesis of 3‐Substituted 3‐Hydroxy‐2‐Oxindoles

“…Liu recently revealed an environmentally friendly asymmetric aldol reaction utilizing double-hydrogen-bonded primary amine organocatalyst XIX in water under mild conditions. This innovative approach yielded enantioenriched 3-hydroxy-2-oxindoles 5 in high yields, reaching up to 98 %, alongside exceptional stereoselectivities of up to 99 : 1 dr and 99 % ee under optimal conditions (Scheme 11) [30] The utilization of chiral thiourea as a catalyst in the aldol reaction of isatin derivatives represents a significant advancement in asymmetric synthesis. [31] Thiourea-based catalysts have gained prominence for their ability to impart stereocontrol in carbon-carbon bond-forming reactions.…”

“…The process resulted in the synthesis of enantioenriched 3-hydroxy-2-oxindoles (S)-5 with high yields, reaching up to 98 %, and exceptional stereoselectivities, with ratios up to 99 : 1 dr and 99 % ee under optimal conditions (Scheme 2). [15] Dr. Jasneet Kaur embarked on her academic journey at Guru Nanak Dev University, Amritsar, where earned her Ph.D. under the guidance of Prof. Swapandeep Singh Chimni in 2017. Her passion for academia led her to assume the role of Assistant Professor in the Department of Chemistry at Khalsa College, Amritsar, starting from August 2018.…”

“…Liu recently revealed an environmentally friendly asymmetric aldol reaction utilizing double‐hydrogen‐bonded primary amine organocatalyst XIX in water under mild conditions. This innovative approach yielded enantioenriched 3‐hydroxy‐2‐oxindoles 5 in high yields, reaching up to 98 %, alongside exceptional stereoselectivities of up to 99 : 1 dr and 99 % ee under optimal conditions (Scheme 11) [30] …”