Ag(i)/PPh₃-catalyzed diastereoselective syntheses of spiro[indole-3,4′-piperidine] derivatives via cycloisomerizations of tryptamine-ynamides

Abstract

A Ag(I)/PPh3-catalyzed chelation-controlled cycloisomerization of tryptamine-ynamide was developed to access the spiro[indole-3,4'-piperidine] scaffold in a racemic and diastereoselective manner. The diastereoselective products were achieved by a chiron approach. Density functional...

Silver-catalyzed synthesis of nitrogen heterocycles: recent advancements

“…Tryptamine-ynamides 128 were subjected to Ag( i )/PPh3-catalyzed cycloisomerization to construct spiro[indole-3,4′-piperidine] skeletons 129 by Liu and research team in 2022. 87 They carried out this chelation-controlled cycloisomerization in racemic and diastereoselective fashion. The racemic cycloisomerization was achieved by reacting tryptamine-ynamide 128 without a chiral center in the presence of 20 mol% AgOTf 26 and 20 mol% PPh 3 at room temperature in toluene for 8 h, and this delivered the desired racemic spiro[indole-3,4′-piperidine] moieties 129 in good to excellent yields (Scheme 47).…”

I2‐Catalyzed Cycloisomerization of Ynamides: Chemoselective and Divergent Access to Indole Derivatives

“…For example, Hsung, Yan, and others disclosed many elegant protocols via 5‐exo‐dig cyclizations of tryptamine‐ynamides, providing versatile spiroindole products or polycyclic indole derivatives (Scheme 1c top left) [20a–f] . Interestingly, 6‐endo ‐ dig cyclizations were developed for the highly efficient and regioselective construction of azepino[4,5‐ b ]indoles and spiro[indole‐3,4′‐piperidine] compounds, respectively, using non‐noble metal catalysts by Ye and Liu (Scheme 1c bottom left) [20g–j] . Despite these promising results, all the reports are limited to 1,2‐vinyl migrations or further R 2 cyclization of spirocyclic intermediates.…”

Computational insight into gold(i)-catalyzed intramolecular regioselectivity of tryptamine-ynamide cycloisomerizations

“…[27][28][29][30][31][32][33][34][35][36][37][38][39] These methods use noble metals and Brønsted acids. [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] Among them, gold(I)-catalyzed reactions represent one of the most efficient methods. However, depending on different substitutions of the alkynyl moiety, the intramolecular addition of functional groups in these transformations typically proceed either at the α-position or at the β-position of the ynamide moiety.…”