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DOI: 10.1055/s-0034-1378628
Diastereoselective Preparation of Enantioenriched Polycyclic Oxoquinolines
Publication History
Publication Date:
18 August 2014 (online)
Significance
Chi and co-workers report the diastereoselective preparation of enantioenriched polycyclic oxoquinolines by the reaction of o-tosylamino enones with activated aryl esters. Ester chemoselective reactivity is achieved through activation of the β-sp3-carbon using an N-heterocyclic carbene precursor. The resulting cyclopenta[c]quinoline-4-one cores are of particular interest due to their ability to act as agonists towards the retinoid X receptor (P. A. Block, R. A. Brown WO2007047946 A3, 2009), their anti-schizophrenia activity (R. A. Beaurang et al. WO2004020591 A3, 2005), and their presence in natural products such as meloscine and scandine.
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Comment
In the presented methodology, a range of enones and esters which include β-alkyl, β-aryl, β-naphthyl, and β-heteroaryl substitution may be used as starting materials. Electron-donating and -withdrawing groups on the aryl rings did not hinder reactivity. In the case of β-alkyl substitution, an appreciable decrease in yield of product was observed. One reported limitation to this method is the failure of the enone with R2 = H to undergo reaction. A mechanism was presented without evidence. In addition, further optimization to reduce catalytic loading of the NHC precursor would have been of value.
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