Finding Lead Catalytic Systems for a Rare Version of Enantioselective Robinson Annulation: Integration of Fluorogenic Assays in Catalyst Screening

Yael Shiloni, Reut Fallek, Moshe Portnoy

Research output: Contribution to journalArticlepeer-review

Abstract

Among the several variants of the highly useful and versatile Robinson annulation, a particular variation that involves ketones reacting with nonenolizable enones, while the α-carbons of the ketones act as nucleophiles at both steps of this cascade process, remains largely unexplored. Moreover, such a catalytic enantioselective reaction is exceptionally rare. While pursuing catalysis of this transformation, we developed two fluorogenic assays that, in combination with other analytic techniques, enabled rapid screening of several sets of catalysts. The first set of polymer-bound aminourea bifunctional organocatalysts was screened using a two-step fluorogenic protocol, designed for slower (e.g., heterogeneous) catalysts. Robinson annulation of acetone with 4′-nitrochalcone formed 3-(4-nitrophenyl)-5-phenyl-2-cyclohexenone, which, after a "developing" reductive treatment, was converted into the corresponding amino derivative, serving as a fluorescent reporter. On the other hand, a range of potentially faster homogeneous catalyst-cocatalyst systems were examined using a direct assay, where 4′-dimethylaminochalcone is converted into the corresponding cyclohexanone fluorescent reporter already upon annulation with acetone. In both cases, the combination of the fluorogenic protocols with high-performance liquid chromatography-based enantiomeric excess estimation enabled identification of lead catalysts, which promoted the enantioselective version of this variant of the annulation.

Original languageEnglish
Pages (from-to)7253-7266
Number of pages14
JournalACS Omega
Volume2
Issue number10
DOIs
StatePublished - 31 Oct 2017

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Chemical Engineering

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