Gold‐Catalyzed Imination/Mannich Reaction Cascades of 3‐En‐1‐ynamides with Anilines and Aldehydes to Enable 1,5‐Nitrogen Functionalizations

Abstract

Gold-catalyzed imination/Mannich reaction cascadeso nr eadily available 3-en-1-ynamides enable the diastereoselectives ynthesis of 1,5-iminoamino compounds in ao ne-pot operation. The reactions workw ell with diversified3 -en-1-ynamides,a ldehydes anda nilines with good to excellent diastereoselectivities.O ur control experiments indicate gold-catalyzed aminations of 3-en-1-ynamides to yield a-imino allylgold intermediates that react subsequently with iminiums to implement the Mannich reactions stereoselectively.T he reactions proceed with anti-selectivity for those 3-en-1-ynamides bearing acyclic alkenes whereas syn-selectivity is seen for theirc ycloalkene-baseda nalogues.A n open-transition state can satisfactorily rationalize these observeds tereoselectivities based on an antiperiplanar conformation.

Gold-Catalyzed syn-1,2-Difunctionalization of Ynamides via Nitrile Activation

“…A recent report by Gagosz et al based on intermolecular dimerization of ynamides followed by intramolecular C–H attack to a vinyl-carbocation intermediate (Scheme B, right), and the demonstration of Hashmi’s on intermolecular trapping of a gold carbene with an ynamide (Scheme B, left), provides a direct access to novel heterocycles . The Au-catalyzed hydroamination of anilines with ynamides (developed by Skrydstrup′s and Liu′s groups), and the intramolecular trapping of vinyl-[Au] species, generated from aniline attack to ynamides, by alkynes, have also been reported . Within this context, trying to devise an intermolecular method based on the concomitant attack of a nucleophile at the α-position of a keteniminium species, obtained in situ from an ynamide under the influence of a gold catalyst, followed by the β-attack of the resulting vinyl-[Au] species to an unsaturated-heteroatom motif, is a challenging endeavor (Scheme C).…”

Gold-Catalyzed Reactions of Specially Activated Alkynes, Allenes, and Alkenes

“…Liu and collaborators have also developed an interesting cascade sequence involving α-imino allyl gold intermediates (Scheme 28). 78 The authors used 3-en- 28). Depending on the substitution of the 3-en-1-ynamide substrates, different products and diastereoselectivities were obtained.…”

“…Liu and collaborators have also developed an interesting cascade sequence involving α-imino allyl gold intermediates (Scheme ). The authors used 3-en-1-ynamides 101 to allow for the diastereoselective synthesis of 1,5-iminoamino derivatives 103 . The reaction involves the addition of aniline 102 to ynamide 101 thus affording α-imino allyl gold intermediate 104 .…”

Gold‐Catalyzed Amination Reactions: Progress and Prospects

“…(Scheme 18). [39] This protocol accomplished the diastereoselective synthesis of 1,5‐iminoamino compounds through a one‐pot operation. Products with excellent diastereoselectivities were achieved from the substrates like diversified 3‐en‐1‐ynamides, aldehydes, and anilines via this method.…”