One-Pot Reductive 1,3-Dipolar Cycloaddition of Secondary Amides: A Two-Step Transformation of Primary Amides.
The one-pot reductive 1,3-dipolar cycloaddition of secondary aromatic N-(trimethylsilylmethyl)amides with reactive dipolarophiles is reported. The method relies on the in situ generation of nonstabilized NH azomethine ylide dipoles via amide activation with triflic anhydride, partial reduction with 1,1,3,3-tetramethyldisiloxane (TMDS), and desilylation with cesium fluoride (CsF). Running under mild conditions, the reaction tolerated several sensitive functional groups and provided cycloadducts in 71-93% yields. The use of less reactive dipolarophile methyl acrylate led to the cycloadduct in only 40% yield. A (Z) geometric intermediate of NH-azomethine 1,3-dipole was postulated to account for the observed higher yields and higher cis diastereoselectivity for the substrates bearing an electron-withdrawing group. This model features an unconventional cyclic transition state via carbanion-aryl ring interaction. Because the starting secondary amides can be prepared from common primary amides, the current method also constitutes a two-step transformation of primary amides.
Department of Chemistry, Fujian Provincial Key Laboratory of Chemical Biology, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, P. R. China.
Pei-Qiang
PQ
Huang
Department of Chemistry, Fujian Provincial Key Laboratory of Chemical Biology, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, P. R. China.
Qi-Wei
QW
Lang
Department of Chemistry, Fujian Provincial Key Laboratory of Chemical Biology, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, P. R. China.
Xiu-Ning
XN
Hu