Reactivity of epoxy-ynamides with metal halides: nucleophile (Br/Cl/OH)-assisted tandem intramolecular 5-exo-digor 6-endo-digcyclisation and AgF₂-promoted oxidation

Abstract

Several metal halides (CuBr, LiCl, CuF2, AgF2) react with epoxy-ynamides to afford 1,3-oxazolidines, 1,4-oxazines or 1,2-dioxo-enamides.

Terminal Alkyne-Assisted One-Pot Synthesis of Arylamidines: Carbon Source of the Amidine Group from Oxime Chlorides

“…Finally, 5r′ will further isomerize into 5r . Therefore, the role of added water in the whole reaction may promote the cleavage of bonds (C–O and N–O) and provide the proton source and OH – anion under such reaction conditions (OH – anion may be afforded from the reaction of Et 3 N and H 2 O), resulting in the generation of the desired product.…”

“…Taking the reaction of eq 7 in Scheme for the formation of 5r as example, phenyl acetylene 1a first reacts readily with tosyl azide 2a to give a ketenimine intermediate A in the presence of CuI and Et 3 N, which then undergo a formal [3 + 2] cycloaddition reaction with in situ-generated nitrile oxide B from oxime halide 3f under Et 3 N to offer intermediate C (HRMS: calcd for C or D [M + H] + , 425.07212; found, 425.07270, see Supporting Information). Subsequently, electronic ring opening of intermediate C occurs with the help of H 2 O (or OH – ) under such reaction conditions, leading to the formation of intermediate D . Intermediate E will be generated by the reaction of OH – (or H 2 O) with intermediate D accompanied by the formation of phenyl acetylene, which will be further recycled, and then, intermediate E will be transformed into the desired isomer amidine 5r′ with the release of O 2 in the presence of OH – (or H 2 O).…”

Ring-Expansion Reactions of Epoxy Amides and Enamides: Functionalized Azetidines, Dihydrofurans, Diazocanes, or Dioxa-3-azabicyclonon-4-enes?

“…We reckoned that epoxy-substituted enamides should provide more diversity since the epoxy ring can undergo expansion to form larger-sized rings. While such a ring expansion protocol using epoxy-ynamides has been efficiently utilized to generate oxazines as well as oxazolidines, enamides are known to be elegant precursors for a variety of transformations that include the synthesis of homopropargyl amides and chiral aliphatic amines …”

3-Trifluoromethyl Pyrrole Synthesis Based on β-CF3-1,3-Enynamides

“…Given the importance of pyrroles heterocycles in medicinal chemistry and agrochemistry as well as in material science, we became interested in the tandem hydroamination and cyclization reaction of β-CF 3 -1,3-enynamides with primary amines (Scheme b) and we are not aware of any reports on the chemistry of β-CF 3 -1,3- enynamides, although the chemistry of their nonfluorinated partners, 1,3-enynamides have been extensively studied . Although the π-donating ability of the nitrogen atom on the alkyne moiety may weaken the electrophilicity of β-CF 3 -1,3-enynamides toward primary amines, however, the base-mediated reversal of regioselectivity in ynamide chemistry caused our interest . We envisioned that a metal-free regioselective 1,4-hydroamination might occur due to the inherited electronic bias of ynamides and the 2-trifluoromethyl-1-alkenes moiety, which will result in the umpolung reactivity of the ynamides moiety .…”

“…Although the π-donating ability of the nitrogen atom on the alkyne moiety may weaken the electrophilicity of β-CF 3 -1,3-enynamides toward primary amines, however, the base-mediated reversal of regioselectivity in ynamide chemistry caused our interest . We envisioned that a metal-free regioselective 1,4-hydroamination might occur due to the inherited electronic bias of ynamides and the 2-trifluoromethyl-1-alkenes moiety, which will result in the umpolung reactivity of the ynamides moiety . The initial resulting allenamide carbanion ( Int-A ) may then be stabilized by the electron-withdrawing group (EWG), followed by proton migration, to afford the trifluoromethylated N -allenamide intermediate ( Int-B ) .…”