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Issue 11, 2013
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Isothiourea-mediated asymmetric Michael-lactonisation of trifluoromethylenones: a synthetic and mechanistic study

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Abstract

HBTM-2.1 promotes the catalytic asymmetric intermolecular Michael-lactonisation of arylacetic acids and trifluoromethylenones in the presence of pivaloyl chloride, giving C(6)-trifluoromethyldihydropyranones with high diastereo- and enantiocontrol (up to 95 : 5 dr and >99% ee) that are readily derivatised to diverse synthetic building blocks containing trifluoromethyl-stereogenicity. Kinetic studies indicate the reaction is first order with respect to both in situ formed mixed anhydride and catalyst concentration, with a primary kinetic isotope effect observed using α,α-di-deuterio 4-fluorophenylacetic acid, consistent with rate determining deprotonation of an intermediate acyl isothiouronium ion.

Graphical abstract: Isothiourea-mediated asymmetric Michael-lactonisation of trifluoromethylenones: a synthetic and mechanistic study

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Publication details

The article was received on 26 Jun 2013, accepted on 01 Aug 2013 and first published on 15 Aug 2013


Article type: Edge Article
DOI: 10.1039/C3SC51791H
Citation: Chem. Sci., 2013,4, 4146-4155
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    Isothiourea-mediated asymmetric Michael-lactonisation of trifluoromethylenones: a synthetic and mechanistic study

    L. C. Morrill, J. Douglas, T. Lebl, A. M. Z. Slawin, D. J. Fox and A. D. Smith, Chem. Sci., 2013, 4, 4146
    DOI: 10.1039/C3SC51791H

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