Novel β-amino Amide Organocatalysts for the Synthesis of Pharmaceutically Relevant Oxindoles

Gavendova, Mariana and Lennon, Claire M. and Coffey, Lee and Manesiotis, Panagiotis and Kinsella, Michael (2019) Novel β-amino Amide Organocatalysts for the Synthesis of Pharmaceutically Relevant Oxindoles. ChemistrySelect, 4 (28). pp. 8246-8254. ISSN 2365-6549

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In this work, a series of novel organocatalysts derived from unique unnatural β-amino acid scaffold were synthesized and further developed to enhance the desired catalytic properties. Their evaluation was carried out in the asymmetric crossed-aldol condensation of isatin and enolizable ketone donors. Following a systematic study of the reaction parameters including variations of additive, solvent, temperature, catalyst loading and substrate scope, (1R,2R)-2-amino-N-((R)-1-phenylethyl)cyclohexane carboxamide 9 proved particularly successful, affording the corresponding 3-hydroxy-3-alkyl-2-oxindole in excellent yield (>99%) and distereoselectivity (>99% dr) with good enantioselective control (up to 52% ee) in the presence of p-nitrophenol and EtOH in <24 h. An added benefit of this catalyst was its catalytic activity and selectivity at room temperature eliminating the requirement of reduced reaction temperatures. This scaffold, comprising of β-amino amide, has not yet been applied in organocatalysis, thus, this is the first reported in this growing area. In mechanistic studies, direct infusion ESI-MS proved a valuable tool forproposal of the catalytic cycle, confirming the formation of 2 key reaction intermediates.

Item Type: Article
Additional Information: Funding Information: The authors would like to thank Waterford Institute of Technology WIT PhD Scholarship program for the financial support of this research (Scholarship No.: WIT/2015/09). Publisher Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/1600
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Depositing User: Admin SSL
Date Deposited: 19 Oct 2022 23:02
Last Modified: 23 Jul 2023 22:45

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