Reversal of nucleophilicity of enamides in water: control of cyclization pathways by reaction media for the orthogonal synthesis of dihydropyridinone and pyrrolidinone Clausena alkaloids.
A highly efficient, metal-free, and divergent method for the synthesis of 3,4-dihydropyridin-2-one and pyrrolidin-2-one Clausena alkaloids and their analogs is reported. While the oxirane-containing enamides underwent the TFA-mediated 6-endo-enamide-epoxide cyclization reaction in Bu(t)OH to produce homoclausenamides, an unprecedented nucleophilic reaction occurred at the alpha-carbon of enamides in water to yield 5-endo-enamide-epoxide cyclization products in excellent yields. The reversal of nucleophilicity of enamides in intramolecular cyclization is discussed in terms of steric and electronic effects of the oxirane-containing enamides.
Yang
Luo
L
Beijing National Laboratory for Molecular Sciences, Laboratory of Chemical Biology, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
Zheng
Qi-Yu
QY
Wang
De-Xian
DX
Huang
Zhi-Tang
ZT
Wang
Mei-Xiang
MX
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D054700:Clausena / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D008968:Molecular Conformation; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000470:Alkaloids; D011728:Pyridones; D011760:Pyrrolidinones; D014867:Water