2 research outputs found
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)Âamides 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 Tf<sub>2</sub>O with BÂ(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>-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)Âdihydrofuran-2Â(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