Sequential transformations enable the facile synthesis of complex target molecules from simple building blocks in a single preparative step. As part of a program concerned with new methods for alkaloid synthesis, we have been utilizing a linked Pummerer/N-acyliminium ion cyclization sequence because this combination offers unique opportunities for the assemblage of complex target molecules. Cyclic 2-methylthio-5-amidofurans possessing tethered π-bonds were prepared from various amido dithioacetals. Upon heating, these systems undergo an intramolecular 4+2-cycloaddition reaction. The initially formed Diels-Alder cycloadduct further rearranges by ring opening of the oxygen bridge followed by a subsequent 1,2-methylthio shift. The method has been successfully applied to several different families of alkaloids.
Pummerer reaction - Mannich reaction - Diels-Alder reaction - cyclization -
N-acylium ions
