An Unconventional Redox Cross Claisen Condensation-Aromatization of 4-Hydroxyprolines with Ketones

Mi Tang, Rengwei Sun, Hao Li, Xinhong Yu, Wei Wang

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Reaction of α-amino acids, particularly prolines and their derivatives with carbonyl compounds via decarboxylative redox process, is a viable strategy for synthesis of structurally diverse nitrogen centered heterocyclics. In these processes, the decarboxylation is the essential driving force for the processes. The realization of the redox process without decarboxylation may offer an opportunity to explore new reactions. Herein, we report the discovery of an unprecedented redox Claisen-type condensation aromatization cascade reaction of 4-substituted 4-hydroxyproline and its esters with unreactive ketones. We found that the use of propionic acid as a catalyst and a co-solvent can change the reaction course. The commonly observed redox decarboxylation and aldol condensation reactions are significantly minimized. Moreover, unreactive ketones can effectively participate in the Claisen condensation reaction. The new reactivity enables a redox cyclization via an unconventional Claisen-type condensation reaction of in situ formed enamine intermediates from ketone precursors with 4-substituted 4-hydroxyproline and its esters as electrophilic acylation partners. Under the reaction conditions, the cascade process proceeds highly regio- and stereoselectively to afford highly synthetically and biologically valued cis-2,3-dihydro-1H-pyrrolizin-1-ones with a broad substrate scope in efficient 'one-pot' operation, whereas such structures generally require multiple steps.

Original languageEnglish (US)
Pages (from-to)8419-8425
Number of pages7
JournalJournal of Organic Chemistry
Volume82
Issue number16
DOIs
StatePublished - Aug 18 2017
Externally publishedYes

ASJC Scopus subject areas

  • Organic Chemistry

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