Metal free regio - and stereoselective semireduction of CF3-substituted N-allenamides.

We developed a chemoselective metal-free access for the 1,2- and 2,3-semireduction of CF3-N-allenamides. The enamide functionality of CF3-substituted N-allenamides could be efficiently reduced by Et3SiH/BF3·OEt2 in total regioselectivity and good stereoselectivity, whereas DBU promoted the isomerization of the resulting allyl amide leading exclusively to the E-configurated enamide.

Silver-Catalyzed Domino Reaction of CF3-Substituted N-Allenamides with Primary Amines for the Construction of 2-Amido-5-fluoropyrroles.

We report herein a domino reaction to construct 2-amido-5-fluoropyrroles from CF3-substituted N-allenamides. The in situ generated gem-difluorinated ene-ynamides derived from CF3-substituted N-allenamides, when subjected to silver catalysis with a primary amine, undergo simultaneous hydroamination of the ynamide moiety followed by a 5-endo-trig addition/ß-fluoride elimination sequence, enabling the construction of 2-amido-5-fluoropyrroles. This transformation features excellent functional group compatibility. By employing 2-aminophenols, functionalized benzo-oxazoles were produced.

Construction of C-N and C-O bonds based on N-allenamide functionalization.

The two-faced reactivity of N-allenamides allows regio- and stereo-controlled functionalization at the α-, ß- and γ-positions of the nitrogen atom. The contingency to obtain either proximal or distal adducts makes these substrates essential for the construction of complex heterocyclic scaffolds. This review covers the recent advances made in the development of new methods involving amination and alkoxylation reactions on N-allenamides leading to a broad array of N-heterocycles. The syntheses reported herein are classified based on their reaction type. In addition, mechanistic perceptions are provided for the majority of the discussed transformations.

Synthesis of Non-natural Aza-Iridoids via Ynamides and Molecular Networking-Based Tracing of Their In Planta Bioconversion.

A synthesis of new-to-nature aza-iridoids via ynamides is presented. ZrCl4 proved to be the best acid to perform this transformation. Various ynamides were accommodated, and seco-iridoids could be obtained as well. Aza-iridoids were infiltrated into leaves of Scrophularia Nodosa, an iridoid-producing plant species. High-resolution mass spectrometry coupled to computational metabolomic approaches was employed for the detection of aza-iridoid bioconversion products.

Regio- and Stereoselective Addition to gem-Difluorinated Ene-Ynamides: Access to Stereodefined Fluorinated Dienes.

The first synthesis of gem-difluorinated ene-ynamides is presented via deprotonation of trifluoromethylated N-allenamides and δ extrusion of fluorine. These highly reactive building blocks, owing to their dual functional groups, offer a unique entry to difluorinated dienes and to stereodefined, monofluoro-substituted dienes. Stereoselective addition to the ynamide moiety led to difluorinated dienes. A stereocontrolled domino δ elimination reaction followed by an addition/elimination sequence from trifluoromethylated N-allenamides provided exclusively stereodefined monofluorinated ene-ynamides.

One-Pot anti-Michael Regio- and Stereoselective Hydroamination of Activated N-Allenamides.

N-Allenamides, substituted by an ester at the γ-position, were obtained through addition of terminal ynamides with ethyl diazoacetate under copper catalysis for the first time. Regio- and stereoselective hydroamination of those activated N-allenamides provided exclusively E-configured captodative enamimes through a one-pot anti-Michael addition. Numerous ynamides as well as various secondary amines were adapted in this process.