Dihydropyridones: catalytic asymmetric synthesis, N- to C-sulfonyl transfer, and derivatizations.

EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, UK.
Angewandte Chemie International Edition (Impact Factor: 11.34). 03/2012; 51(15):3653-7. DOI: 10.1002/anie.201109061
Source: PubMed

ABSTRACT Benzotetramisole (1) promotes the reaction of ammonium enolates derived from arylacetic acids with N-tosyl-α,β-unsaturated ketimines, thus giving dihydropyridones with high diastereo- and enantiocontrol. These products readily undergo N- to C-sulfonyl photoisomerization and are derivatized to afford stereodefined piperidines and tetrahydropyrans.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Electron-deficient 1-aza-1,3-butadienes containing a 1,2-benzoisothiazole-1,1-dioxide or 1,2,3-benzoxathiazine-2,2-dioxide motif act as regio- and chemoselective dienophiles in normal-electron-demand Diels-Alder reactions with HOMO-raised trienamines, rather than typical 4π-participation in inverse-electron-demand versions. The enantioenriched cycloadducts could be efficiently converted to spiro or fused frameworks with high structural and stereogenic complexity by a sequential aza-benzoin reaction or other transformations.
    Organic Letters 11/2013; · 6.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: With the intention of improving synthetic efficiency, organic chemists have turned to bioinspired organocascade or domino processes that generate multiple bonds and stereocentres in a single operation. However, despite the great importance of substituted cyclopentanes, given their prevalence in complex natural products and pharmaceutical agents, the rapid, enantioselective assembly of these carbocycles lags behind cyclohexanes. Here, we describe a Michael-aldol-β-lactonization organocascade process for the synthesis of complex cyclopentanes utilizing chiral α,β-unsaturated acylammonium intermediates, readily generated by activation of commodity unsaturated acid chlorides with chiral isothiourea catalysts. This efficient methodology enables the construction of two C-C bonds, one C-O bond, two rings and up to three contiguous stereogenic centres delivering complex cyclopentanes with high levels of relative and absolute stereocontrol. Our results suggest that α,β-unsaturated acylammonium intermediates have broad utility for the design of organocascade and multicomponent processes, with the latter demonstrated by a Michael-Michael-aldol-β-lactonization.
    Nature Chemistry 12/2013; 5(12):1049-1057. · 21.76 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Acids to bases: The synthesis of 2,4,6-trisubstituted pyridines from (phenylthio)acetic acid and a range of α,β-unsaturated ketimines is reported. This process proceeds by intermolecular Michael addition/lactamization, thiophenol elimination, and N- to O-sulfonyl migration, giving 2-sulfonate-substituted pyridines which are readily derivatized to generate structural diversity.
    Angewandte Chemie International Edition 09/2013; 52(44). · 11.34 Impact Factor