A Short Synthesis of Unsymmetrical 2,3-Dihydrothiopyran-4-ones

Significance

This report represents the first stepwise synthesis of unsymmetrical 2,6-disubstituted 2,3-dihydrothiopyran-4-ones. In contrast to the conjugate addition of nitrogen nucleophiles to ynones which result in the formation of the thermodynamically favored (E)-enamines (T. J. J. Müller and co-workers Eur. J. Org. Chem. 2005, 1834-1848), the present reaction involves a double thia-Michael process on the intermediate enynone affording unsymmetrical 2,6-disubstituted 2,3-dihydrothiopyran-4-ones in good to excellent yields for the single step (60-95%). Acrolein was used in place of cinnaminaldehyde in several examples. However, in these cases, low yields for the sulfide addition step were observed as the freshly prepared enynones were found to be unstable at ambient and even lower temperatures.