Synthesis of substituted pyridines via regiocontrolled [4 + 2] cycloadditions of oximinosulfonates

Abstract

Diels-Alder cycloadditions of oximinosulfonate 8 with a variety of 1, 3-dienes proceed with regiochemistry opposite to that observed with conventional imino dienophiles, providing expeditious synthetic routes to substituted pyridines, tetrahydropyridines, and pyrrolines. The oximinosulfonate 8 is prepared in one convenient synthetic operation from Meldrum's acid and reacts with conjugated dienes at -78 C in the presence of 2 equiv of dimethylaluminum chloride to afford [4 + 2] cycloadducts in good to excellent yield. Exposure of these cycloadducts to the action of NaOMe and JV-chlorosuccinimide in methanol-THF at room temperature then produces substituted pyridines. The utility of this new two-step annulation protocol is demonstrated in total syntheses of the pyridine alkaloids fusaric acid and (S)-(+)-fusarinolic acid. Heating the [4 + 2] cycloadducts derived from 8 in a mixture of acetonitrile and pH 7 phosphate buffer induces an unusual Stieglitztype rearrangement leading to the formation of interesting spirobicyclic pyrrolines. © 1998 American Chemical Society.