The first synthesis of gem-difluorinated ene-ynamides is presented via deprotonation of trifluoromethylated Nallenamides and 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  elimination reaction followed by an addition/elimination sequence from trifluoromethylated N-allenamides provided exclusively stereodefined monofluorinated ene-ynamides. ASSOCIATED CONTENTSupporting Information. The Supporting Information is available free of charge on the ACS Publications website. General methods, synthetic procedures, characterization data and copies of 1 H, 13 C and 19 F NMR spectra and X-ray crystallography data.CCDC 2164358 and 2155397 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk

The two-faced reactivity of N-allenamides allows regio-and stereo-controlled functionalization on the -, - and γ-positions of the nitrogen atom. The contingency to obtain either proximal or distal adducts, makes those...

We report herein a domino reaction to construct 2-amido-5-fluoropyrroles from CF 3 -substituted N-allenamides. The in situ generated gem-difluorinated ene-ynamides derived from CF 3 -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/β-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.

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.

A synthesis of new-to-nature aza-iridoids via ynamides is presented. ZrCl 4 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.