Using the Pummerer cyclization-deprotonation-cycloaddition cascade of imidosulfoxides for alkaloid synthesis.
The Pummerer reaction of imidosulfoxides bearing tethered alkenyl groups has been employed for the synthesis of several alkaloids. The required imidosulfoxides necessary for the cascade sequence were easily obtained by heating the appropriate amide with (ethylsulfeny)acetyl chloride followed by sodium periodate oxidation. The initially formed thionium ion, obtained by treating the imidosulfoxide with acetic anhydride and p-toluenesulfonic acid, reacts with the neighboring imido group, and the resulting oxonium ion undergoes subsequent deprotonation to produce an isomünchnone dipole. This mesoionic betaine intermediate undergoes ready intramolecular dipolar cycloaddition across the neighboring pi-bond. Exposure of the resulting cycloadducts to additional acetic anhydride leads to ring opening and formation of a 5-acetoxy-substituted 2(1H)-pyridone. This six-ring heterocyclic system constitutes a valuable building block for the synthesis of a variety of pyridine, quinolizidine, and clavine alkaloids. The cyclization-deprotonation-cycloaddition cascade has been successfully applied to the synthesis of the naturally occurring alkaloids onychnine, dielsiquinone, (+/-)-lupinine, (+/-)-anagyrine, (+/-)-pumiliotoxin C, and (+/-)-costaclavine.
Padwa
A
A
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
Heidelbaugh
T M
TM
Kuethe
J T
JT
D000470:Alkaloids / Q000138:chemical synthesis*; D001392:Azocines; D001938:Brazil; D003500:Cyclization; D004873:Ergolines / Q000138:chemical synthesis; D007094:Imides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010946:Plants, Medicinal / Q000737:chemistry; D011522:Protons; D011804:Quinolines; D011807:Quinolizines; D013034:Sparteine / Q000031:analogs & derivatives; D013454:Sulfoxides / Q000737:chemistry*; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D004873:Ergolines; D007094:Imides; D011522:Protons; D011804:Quinolines; D011807:Quinolizines; D013034:Sparteine; D013454:Sulfoxides; C011093:pumiliotoxin C; C015971:lupinine; D000093843:Quinolizidine Alkaloids; C033546:costaclavin; C012736:anagyrine