DMSO/Tf₂O-mediated cross-coupling of tryptamine with substituted aniline to access C3a–N1′-linked pyrroloindoline alkaloids

Abstract

The cross-coupling of tryptamine with substituted aniline to access C3a-nitrogen-linked pyrroloindolines has been developed via the consecutive cyclization of tryptamine with DMSO/Tf2O and the substitution of 3a-pyrroloindolylthionium intermediate with aniline. The use of 2,3-dihydrotryptamine instead of aniline enabled easy access to 3a-(1-indolyl)pyrroloindoline and the concise synthesis of C3a-N1'-linked pyrroloindoline alkaloid (±)-psychotriasine was accomplished.

Enantioselective Synthesis of Pyrroloindolines via Noncovalent Stabilization of Indole Radical Cations and Applications to the Synthesis of Alkaloid Natural Products

“…Lastly, we also adapted this method to develop a concise enantioselective synthesis of psychotriasine, another dimeric pyrroloindoline natural product that features an unusual C–N linkage. , Using the mesolytic cleavage conditions described above with ortho -iodoaniline as the nucleophile resulted in formation of expected N -aryl pyrroloindoline 22 in 64% yield. By adopting a strategy originally developed by Baran in his synthesis of psychotriasine, the iodoaniline was subjected to a Larock annulation with alkyne 30 to furnish the core of the natural product .…”

Lewis Acid Catalyzed Displacement of Trichloroacetimidates in the Synthesis of Functionalized Pyrroloindolines

“…Similar systems have been reported to be unstable by other researchers. 9a However when 5-bromoindoline or 5,7-dibromoindoline ( 24a ) were employed satisfactory yields were obtained (entries 8 and 9), as the bromine atoms block the undesired alkylation of the aromatic ring and slow oxidation of the indoline to the indole. Employing an indole instead of the indoline provided a complex mixture of products.…”

Triflic Anhydride (Tf2O)-Activated Transformations of Amides, Sulfoxides and Phosphorus Oxides via Nucleophilic Trapping

“…Kawasaki and co-workers developed a thionium-reagentmediated cross-coupling reaction of tryptamine 57a with anilines to synthesize 3a-substituted pyrroloindolines 57bg (Scheme 57). 99 The screening of N-nucleophiles revealed that electron-deficient para-substituents on aniline derivatives such as p-cyano-, p-methoxycarbonyl-, and p-bromoanilines provided pyrroloindoline products in excellent yields. However, bulky N-nucleophiles and N-alkyl nucleophiles reduced the product yield of 57f, presumably due to steric hindrance.…”