Synthesis of 1-haloethenamides from ynamide through halotrimethylsilane-mediated hydrohalogenation

Chemo- and Stereoselective Synthesis of Fluorinated Enamides from Ynamides in HF/Pyridine: Second-Generation Approach to Potent Ureas Bioisosteres

“…Since this class of enamides is virtually unknown, we recently reported the first general synthesis of α-fluoroenamides via a superacid-catalyzed hydrofluorination of ynamides A − through the intermediacy of a keteniminium ion B (Scheme ) . Although this method was shown to have a rather broad substrate scope, some acid-sensitive and chiral ynamides were not well tolerated under these conditions.…”

N‐Ethynylation of Anilides Decreases the Double‐Bond Character of Amide Bond while Retaining trans‐Conformation and Planarity

“…To check the reactivity of amides, we exposed 3 and 4 to the same conditions (at 80 8C);t his resulted in the recovery of most of the reactants in the case of 3, and partial recovery in the case of 4.N otably,s elective cleavage of the NÀC(sp) bond was also possible (Scheme 2b). Iwasawa and co-workersr eported that TMSBrr eacted with tosyl ynamide to afford b-bromo alkene compounds, [27] and observed dealkynylationb yu sing methanol as an ucleophile. Similarly,n on-nucleophilic TMSOTf activated the triple bond of N-alkynyl anilide derivatives, probablyt hrough coordinationt o the carbonyl group, furnishing anilides with the NÀC(sp) bond cleaved after treatment with methanol.…”

“…Notably, selective cleavage of the N−C(sp) bond was also possible (Scheme b). Iwasawa and co‐workers reported that TMSBr reacted with tosyl ynamide to afford β‐bromo alkene compounds, and observed dealkynylation by using methanol as a nucleophile. Similarly, non‐nucleophilic TMSOTf activated the triple bond of N ‐alkynyl anilide derivatives, probably through coordination to the carbonyl group, furnishing anilides with the N−C(sp) bond cleaved after treatment with methanol.…”

α-Haloenamides: Synthesis and Subsequent Transformations

“…Surprisingly, TMSCl quickly reacted with N -tosylethynamides (Scheme 6 ). 9 This points to the importance of complexation between ynamide and TMSX in this process; thus, the sterically unhindered ethynamide tightly coordinates to TMSCl, which readily activates the Si–Cl bond. 1-Iodo- and 1-bromoethenamides can also be prepared according to the same procedure, starting with N -tosylethynamides.…”

“…This methodology developed by Iwasawa and co-workers showed excellent substrate compatibility. Disubstituted ynamides 8 and terminal N -tosyl-ynamides 9 were used as starting materials, the protocol was also applied to N -tosylated buta-1,3-diyne-1,4-diamines. 10…”