ABSTRACT
The scope and limitations of a photoinitiated N- to C-sulfonyl migration process within a range of dihydropyridinones is assessed. This sulfonyl transfer proceeds without erosion of either diastereo- or enantiocontrol, and is general across a range of N-sulfonyl substituents (SO2R; R = Ph, 4-MeC6H4, 4-MeOC6H4, 4-NO2C6H4, Me, Et) as well as C(3)-(aryl, heteroaryl, alkyl and alkenyl) and C(4)-(aryl and ester) substitution. Crossover reactions indicate an intermolecular step is operative within the formal migration process, although no crossover from C-sulfonyl products was observed. EPR studies indicate the intermediacy of a sulfonyl radical and a mechanism is proposed based upon these observations.
ABSTRACT
The exploration and expansion of the scope of the isothiourea-mediated synthesis of dihydropyridinones is presented. The use of ketimines derived from α,ß-unsaturated γ-ketoesters as the Michael acceptor in a Michael addition/lactamisation cascade gives access to a range of dihydropyridinones with high enantioselectivity. The nature of the N-sulfonyl group present on the ketimine is extensively investigated, with further studies into derivatisation of the dihydropyridinone core also reported.
ABSTRACT
A one-pot isothiourea-mediated Michael addition/lactonization/thiol elimination cascade sequence for the formation of 4,6-disubstituted and 3,4,6-trisubstituted 2-pyrones from (phenylthio)acetic acids and α,ß-unsaturated trifluoromethyl ketones is described. The synthesis of a COX-2 inhibitor and the wide-ranging derivatization of the 2-pyrone moiety to trifluoromethyl substituted aromatics and heteroaromatics is also disclosed.
Subject(s)
Cyclooxygenase 2 Inhibitors/chemical synthesis , Hydrocarbons, Fluorinated/chemical synthesis , Pyrones/chemical synthesis , Thiourea/chemistry , Catalysis , Cyclooxygenase 2 Inhibitors/chemistry , Hydrocarbons, Fluorinated/chemistry , Molecular Structure , Pyrones/chemistryABSTRACT
Acids to bases: The synthesis of 2,4,6-trisubstituted pyridines from (phenylthio)acetic acid and a range of α,ß-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.
