One‐Pot Aminoethylation of Indoles/Pyrroles with Alkynes and Sulfonyl Azides

Abstract

A general and efficient one-pot aminoethylation of substituted indoles/pyrroles was accomplished for the synthesis of various tryptamine derivatives employing a combination of alkynes and sulfonyl azides as readily accessible aminoethylating agents. The reaction features a successful integration of copper-catalyzed alkyne and azide cycloaddition to N-sulfonyl-1,2,3-triazole, rhodium-catalyzed selective insertion of α-iminocarbenes onto the C3-H bond of indoles, and reduction of the resultant enamides to tryptamine derivatives employing either NaCNBH3 or palladium catalyst, in one-pot. The reaction also showed excellent functional-group tolerance and allowed the synthesis of various substituted tryptamines in good to excellent yield. This transformation constitutes a one-pot formal regioselective functionalization of terminal alkynes. Utility of the synthesized tryptamine was further demonstrated in the synthesis of dihydro-β-carboline and tryptoline.

Stereoselective Synthesis of (Z)‐β‐Enamido Triflates and Fluorosulfonates from N‐Fluoroalkylated Triazoles

“…N ‐Sulfonyl triazoles, precursors of azavinyl carbenes, are known to undergo a variety of rhodium‐catalyzed reactions. They have been used for the preparation of different types of heterocycles, N ‐sulfonyl‐containing compounds, and for stereoselective synthesis of 2,2‐diaryl or 2‐alkyl‐2‐aryl‐ substituted N ‐sulfonyl enamides (Figure B) . We have recently shown that N ‐fluoroalkyl triazoles prepared by a [3+2] cycloaddition of stable and safe azido(per)fluoroalkanes and alkynes are efficiently transformed to new N ‐fluoroalkyl heterocycles via rhodium carbenoids .…”

“…They have been used for the preparation of different types of heterocycles, N-sulfonyl-containing compounds, [27] and for stereoselectives ynthesiso f2 ,2-diaryl or 2-alkyl-2-aryl-substituted N-sulfonyl enamides ( Figure 1B). [28][29][30][31][32][33] We have recently shown that N-fluoroalkyl triazoles prepared by a[ 3 + +2] cycloaddition of stable and safe azido(per)fluoroalkanes anda lkynes [34][35][36] are efficiently transformed to new N-fluoroalkyl heterocycles via rhodiumc arbenoids. [37,38] However,t he reactivity profiles of Nfluoroalkyl triazoles and N-sulfonyl triazoles are markedlyd ifferent.…”

A General Proline‐Catalyzed Synthesis of 4,5‐Disubstituted N‐Sulfonyl‐1,2,3‐Triazoles from 1,3‐Dicarbonyl Compounds and Sulfonyl Azide

“…Next, denitrogentaive C−H bond insertion of 3 a with N , N ‐diethyl aniline 6 in the presence of 4 mol % of Rh 2 (Oct) 4 furnished the tetra ‐substituted enamide derivative 13 in 59 % yield . Likewise, replacement of N , N ‐diethyl aniline with N ‐methylindole 14 under the similar conditions afforded the corresponding tetra ‐substituted enamides 15 in 76 % yield …”

Ligand‐based Modeling for the Prediction of Pharmacophore Features for Multi‐targeted Inhibition of the Arachidonic Acid Cascade

“…The compounds N‐(2‐(1H‐Indol‐3‐yl)‐2‐phenylethyl)‐4‐methylbenzenesulfonamide ( C1 ) and 2‐(3,4‐dichlorophenyl)‐2(4‐methoxyphenyl)ethanol ( C2 ) were synthesised and their inhibition of the formation of prostaglandin E2, product of mPGES‐1, was estimated as described previously . Hela cells were cultured in Dulbecco's Modified Essential Medium supplemented with 10 % Fetal bovine serum under 5 % CO2.…”