Recent advances in the chemistry of ynamines and ynamides

Copper Salt‐Catalyzed Azide‐[3 + 2] Cycloadditions of Ynamides and Bis‐Ynamides

“…As shown in Scheme 1, the CuSO 4 ·5 H 2 O-catalyzed cycloaddition of terminal ynamide 5 with BnN 3 led to chiral amide-substituted triazole 7 in 82 % yield as the only regioisomer using Fokin-Sharpless conditions. [15] The catalytic sequence likely proceeds through a Cu(I) catalytic species generated via reduction of CuSO 4 . [15] The high level of regioselectivity is likely a result of the copper catalysis and steric factors because of the large oxazolidinone motif.…”

“…[4][5][6][7][8] Specifically, we have examined the classic Huisgens azide-[3 + 2] cycloaddition [9][10][11] given its current resurgence facilitated by the "click" chemistry concept. [12] Recently, Cintrat [13] and we [14] independently communicated azide-[3 + 2] cycloadditions employing ynamides in a highly regioselective manner that favors 1,4-adducts (1 + 2!3 in Figure 1).…”

The intermolecular hydro-oxycarbonylation of internal alkynes: current state of the art

“…76 As shown in Scheme 7, the addition of the carboxylic acid to the C≡C of the substrates proceeded in a completely regio-and stereoselective manner, providing the α-acyloxyenamides 12 in moderate to high yields. It is worth noting that, while the regioselectivity observed in these reactions is not surprising since the addition of heteroatom nucleophiles to the triple bond of ynamides usually occurs α to the nitrogen atom, [77][78][79] the stereochemical outcome (syn addition) is opposite to the examples just discussed above (anti addition). Although the authors did not dare to propose a conclusive mechanism, they briefly commented two different possibilities, involving: (i) the initial generation of a palladium-hydride intermediate by oxidative addition of the carboxylic acid to in situ formed Pd(0) species, followed by hydropalladation of the ynamide and final C-O reductive elimination, or (ii) the addition of the carboxylate anion to in situ generated N-acylketeniminium intermediates.…”

“…This is the case of ynamides 11, in which the presence of a nitrogen atom adjacent to the alkyne function renders the C≡C bond much more reactive compared to that of standard alkynes. [77][78][79] In this context, Hu, Bi and coworkers demonstrated that no metals are needed to promote the addition of carboxylic acids to ynamides 11, the formation of compounds 12 (see Scheme 7) taking place just by heating 11 in the presence of the corresponding acid (1.5 equiv.) in toluene at 100 °C (52-99% isolated yields after 1 h).…”

Novel ynamide structural analogues and their synthetic transformations

“…Ynamides 1 (Scheme 1), the electron-deficient alternatives of the important but labile ynamines, [1][2][3][4][5][6][7][8][9][10][11][12][13][14] represent one of the most significant and versatile N-containing building blocks in organic synthesis. [15][16][17] Particularly, in the past 15 years, interests in this versatile building block have raised dramatically.…”