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 <i>N</i>-(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 (<i>Z</i>) geometric intermediate of NH-azomethine 1,3-dipole was postulated to account for the observed higher yields and higher <i>cis</i> 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

Substrate-Controlled Chemoselective Reactions of Isocyanoacetates with Amides and Lactams

Versatile and chemoselective C–C bond forming methods for the one-pot transformation of amides into other classes of compounds are highly demanding. In this report, we demonstrate the reductive addition of isocyanoacetates to common amides and lactams to produce 5-methoxyoxazoles or bicyclic imidazolines. This one-pot procedure involves partial reduction of amides with Schwartz reagent and chemoselective addition of the carbon of isocyanide group or α-carbon in isocyanoacetates. The quite different reactivity of the isocyanoacetate is due to the different steric hindrance of the amides and lactams

Substrate-Controlled Chemoselective Reactions of Isocyanoacetates with Amides and Lactams

Versatile and chemoselective C–C bond forming methods for the one-pot transformation of amides into other classes of compounds are highly demanding. In this report, we demonstrate the reductive addition of isocyanoacetates to common amides and lactams to produce 5-methoxyoxazoles or bicyclic imidazolines. This one-pot procedure involves partial reduction of amides with Schwartz reagent and chemoselective addition of the carbon of isocyanide group or α-carbon in isocyanoacetates. The quite different reactivity of the isocyanoacetate is due to the different steric hindrance of the amides and lactams