Intramolecular Gold-Catalyzed and NaH-Supported Cyclization Reactions of N-Propargyl Indole Derivatives with Pyrazole and Pyrrole Rings: Synthesis of Pyrazolodiazepinoindole, Pyrazolopyrazinoindole, and Pyrrolopyrazinoindole

Abstract

Gold-catalyzed and NaH-supported intramolecular cyclization of N-propargyl indole derivatives with pyrazole and pyrrole units attached to indole is described. An efficient route to the synthesis of pyrazolodiazepinoindole, pyrazolopyrazinoindole, and pyrrolopyrazinoindole has been established. First, N-propargyl 2-(1H-pyrazol-5-yl)-1H-indole and 2-(1H-pyrrol-2-yl)-1H-indole were synthesized. Introduction of various substituents into the alkyne functionality was accomplished by Sonogashira cross-coupling reaction. Gold-catalyzed cyclization of pyrazoles having a terminal alkyne afforded the 6-exo-dig cyclization product. However, exclusive formation of 7-endo-dig cyclization products was observed with internal alkynes. On the other hand, cyclization with NaH only resulted in the formation of 6-exo-dig cyclization products regardless of the substitution of the alkyne functionality. Allenic intermediates were postulated for this outcome.

A Concise Review on the Synthesis and Reactions of Pyrazolopyrazine Heterocycles

“…Intermolecular gold‐catalyzed cyclization of pyrazole derivative 140 into 5‐methyl‐2‐phenylpyrazolo[5′,1′:3,4]pyrazino[1,2‐ a ]indole (141) was achieved by gold (III) chloride at room temperature (Scheme ) .…”

“…Similarly, NaH‐supported intramolecular cyclization of pyrazoles 142a–h afforded the corresponding allene 143 that was converted into 5‐substituted‐2‐phenyl pyrazolo[5′,1′:3,4]pyrazino[1,2‐ a ]indole 144a–h in good yields (Scheme ) .…”

Synthesis and Reactivity of Oxazinoindolones via Regioselective 6‐exo‐dig Iodolactonization

“…By the same methodology previously described for commercial pyrrole 18 (N-propargylation with propargyl bromide; saponification with KOH), we obtained the pyrrole acid 20 in good yield (Scheme 13). [14,44] Under the previously used iodocyclization conditions [Na2CO3 (3 equiv. ), I2 (1.5 equiv.)…”

“…Only the 1-(but-2-ynyl)-1H-indole-2-carboxylic acid 7i was already described and is in accordance with the literature. [14,44] 3- Iodo-1-(prop-2-yn-1-yl 9, 129.9, 128.8, 126.1, 123.1, 121.8, 111.5, 79.6, 74.7, 68.9, 34. 7, 148.4, 144.8, 134.0, 127.0, 124.5, 101.5, 100.5, 91.6, 79.6, 74.7, 69.3, 35. 13 C NMR (75 MHz, DMSO-d6): δ = 161. 9, 155.3, 133.1, 130.3, 128.9, 117.3, 112.8, 103.1, 79.6, 74.7, 68.1, 55.4, 34.8 Fluoro-3-iodo-1-(prop-2-yn-1-yl -7-methoxy-1-(prop-2-yn-1yl 13 C NMR (75 MHz, DMSO-d6): δ = 162.…”

Cu nanoparticles immobilized on montmorillonite by biquaternary ammonium salts: a highly active and stable heterogeneous catalyst for cascade sequence to indole-2-carboxylic esters

“…23,24 As far as we all know, many indole-2-carboxylic esters and its derivatives are used as powerful precursors for antimicrobial, anticonvulsant and anticancer drugs. [25][26][27][28] Usually, the synthesis of indole-2carboxylic esters contains a build of C-N bond. Recently, Cu is reported as a cheap catalyst for the synthesis of indole-2carboxylic esters.…”