Mn(III)/Cu(II)-mediated oxidative radical cyclization of alpha-(Methylthio)acetamides leading to erythrinanes.
Treatment of N-[2-(3,4-dimethoxyphenyl)ethyl]-alpha-(methylthio)acetamide 3 with Mn(OAc)3 in the presence of Cu(OAc)2 gave tetrahydroindol-2-one 4, which then cyclized with Mn(OAc)3 to give 4-acetoxyerythrinane 5. A similar reaction of the 3,4-methylenedioxyphenyl congener 8 also gave tetrahydroindol-2-one 9, which, however, gave only a trace amount of the Mn(OAc)3-mediated cyclization product 11 and afforded the oxidation product 10. On the basis of these results, formation of 5 from 4 was thought to proceed via nucleophilic attack of the pyrrole ring on the cation-radical lX, generated by a single electron-transfer reaction of the acetoxy-substituted intermediate V. Treatment of compound 16 with Mn(OAc)3/Cu(OAc)2 gave no erythrinane derivative with recovery of the starting material, indicating that the presence of a methylthio group of 4 is essential for effecting the formation of erythrinane 5. On the other hand, treatment of 3 with Mn(OAc)3 using Cu(OTf)2 as an additive in place of Cu(OAc)2 gave another erythrinane 17. This method was applied to a formal synthesis of 3-demethoxyerythratidinone (20), a naturally occurring Erythrina alkaloid.
Chikaoka
Shiho
S
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Japan.
Toyao
Atsushi
A
Ogasawara
Mizuho
M
Tamura
Osamu
O
Ishibashi
Hiroyuki
H
D000081:Acetamides / Q000737:chemistry*; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D003300:Copper; D018360:Crystallography, X-Ray; D003500:Cyclization; D004895:Erythrina / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis*; D008345:Manganese; D010084:Oxidation-Reduction; D010946:Plants, Medicinal / Q000737:chemistry*
D000081:Acetamides; D006576:Heterocyclic Compounds, 4 or More Rings; D008345:Manganese; D003300:Copper