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

Mild Metal-Free Hydrosilylation of Secondary Amides to Amines

The combination of amide activation by Tf₂O with B­(C₆F₅)₃-catalyzed hydrosilylation with TMDS constitutes a method for the one-pot reduction of secondary amides to amines under mild conditions. The method displays a broad applicability for the reduction of many types of substrates, and shows good compatibility and excellent chemoselectivity for many sensitive functional groups. Reductions of a multifunctionalized α,β-unsaturated amide obtained from another synthetic methodology, and a C–H functionalization product produced the corresponding amines in good to excellent yield. Chemoselective reduction of enantiomeric pure (ee >99%) tetrahydro-5-oxo-2-furaneamides yielded 5-(aminomethyl)­dihydrofuran-2­(3<i>H</i>)-ones in a racemization-free manner. The latter were converted in one pot to <i>N</i>-protected 5-hydroxypiperidin-2-ones, which are building blocks for the synthesis of many natural products. Further elaboration of an intermediate led to a concise four-step synthesis of (−)-<i>epi</i>-pseudoconhydrine