Total synthesis of (+/-)-didehydrostemofoline (asparagamine A) and (+/-)-isodidehydrostemofoline.

ABSTRACT

The first total syntheses of (+/-)-didehydrostemofoline (1) and (+/-)-isodidehydrostemofoline (3) are reported. The synthesis begins with the Diels-Alder reaction of readily available pyrrole 9 and ethyl (E)-3-nitroacrylate, the latter serving as a regioinverted equivalent of ketene. After hydrogenation to prevent retro-Diels-Alder reaction, the major cycloadduct is transformed to 7-azabicyclo[2.2.1]heptanol 14. Aza-Cope-Mannich reaction of the formaldiminium derivative of 14 delivers 1-azatricyclo[5.3.0.04.10]decane 15, which in 15 additional steps is converted to 1 and 3.