Platform of Oxidative Transformation of α-Methyl Secondary Enaminones toward Tetrahydropyridines

In this paper, the application of α-methyl secondary enaminones in the synthesis of tetrahydrofuropyridines is described. The key step of the methodology is the in situ generation of 1-azadiene from oxidation of α-methyl secondary enaminone, followed by a subsequent inverse-electron-demand hetero-Diels-Alder reaction proceeded to give the desired product. Mechanistic studies and density functional theory (DFT) calculations revealed the detailed reaction pathway. Gram-scale preparation experiments and further transformation of the product demonstrate the potential applicability of this method. In addition, the amide derivatives could be obtained by employing β-methyl secondary enaminones as substrates under similar oxidative conditions. The present work opens a new window to the application of rarely reported α-methyl secondary enaminones.