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

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 de...

Full description

Saved in:
Bibliographic Details
Published inChemical science (Cambridge) Vol. 4; no. 11; pp. 4146 - 4155
Main Authors Morrill, Louis C, Douglas, James, Lebl, Tomas, Slawin, Alexandra MZ, Fox, David J, Smith, Andrew D
Format Journal Article
LanguageEnglish
Published 01.01.2013
Subjects
Anhydrides
Asymmetry
Catalysis
Catalysts
Chlorides
Isotope effect
Reaction kinetics
Online AccessGet full text

Cover

More Information
Summary: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 situformed mixed anhydride and catalyst concentration, with a primary kinetic isotope effect observed using alpha , alpha -di-deuterio 4-fluorophenylacetic acid, consistent with rate determining deprotonation of an intermediate acyl isothiouronium ion.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
ObjectType-Article-1
ObjectType-Feature-2
ISSN:2041-6520
2041-6539
DOI:10.1039/c3sc51791h