Chemo- and Stereoselective Transition-Metal-Free Amination of Amides with Azides

Abstract

The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The amide is used as the limiting reagent, and through simple variation of the azide pattern, various differently substituted aminated products can be obtained. The reaction is fully chemoselective for amides even in the presence of esters or ketones and lends itself to preparation of optically enriched products.

A Novel Class of 7‐Membered Heterocyclic Compounds

“…[2] In doing so, the amide is transformed into an α-trifloxyenamine 2, which resides in a biased equilibrium with the keteniminium salt 3. The latter, a highly electrophilic species, can be intercepted by several nucleophiles, including nucleophilic oxidants, [3][4][5][6][7] and enables a range of unconventional reactivity profiles for the atoms surrounding the original amide functionality. [8][9][10][11][12] The capture of the central electrophilic atom of the keteniminium by modestly nucleophilic entities such as alkenes (in formal [2+2] cycloaddition reactions [13,14] or other ring-forming events) [15] or ethers [16,17] is a well-documented phenomenon.…”

Synthesis of γ-pyrones via decarboxylative condensation of β-ketoacids

“…This approach was successfully applied by Moghaddam et al in a microwave-assisted synthesis of alkyl-substituted γ -pyrones from anhydrides and carboxylic acids [20]. During our investigations aiming to develop the potential of trifluoromethanesulfonic anhydride (Tf 2 O) as an electrophilic-activating reagent of unsaturated C–O bonds [21–26], we discovered that β -ketoacids can undergo an auto-condensation to form disubstituted γ -pyrones. This simple transformation, which we wish to present herein, allows the obtention of alkyl- and aryl-substituted heterocycles.…”

Acid/Base‐Co‐catalyzed Direct Oxidative α‐Amination of Cyclic Ketones: Using Molecular Oxygen as the Oxidant

“…[5,6] Recently, an elegant a-amination of amides was reported under transition-metalfree conditions in the presence of trifluoromethanesulfonic anhydride by Maulide and co-workers, in which organic azides were employed as nitrogen sources. [7] Obviously, the most simple and efficient route for the synthesis of a-amino ketones is the direct oxidative amination of a-C(sp 3 )ÀH bonds of carbonyl com-pounds. However, in the a-amination reactions, transition metal catalysts and chemical oxidants are generally required (Scheme 1, previous work).…”

“…Initially, in the presence of TfOH, the enamine intermediate A is formed by the condensation of 1 with TMP with the liberation of H 2 O. Subsequently, the ammoniumyl radical cation intermediate B, generated by the oxidation of amines 2 through a single-electron transfer (SET) process, [10,12,13] 7). When benzylamines were used as coupling partners, benzylamines 2 t-v were oxidized by O 2 through a SET process, followed by the hydrolysis, to give the corresponding aromatic aldehydes.…”