Brønsted Acid Mediated Alkenylation and Copper-Catalyzed Aerobic Oxidative Ring Expansion/Intramolecular Electrophilic Substitution of Indoles with Propargyl Alcohols: A Novel One-Pot Approach to Cyclopenta[c]quinolines

Abstract

Copper-catalyzed oxidative ring-expansion/intramolecular electrophilic substitution of 3-dienylindoles leading to cyclopenta[c]quinolines and 3-indenylindoles under aerobic conditions is described. The precursors, 3-dienylindoles, are formed via Friedel-Crafts alkenylation followed by isomerization reactions of 2-substituted indoles with tertiary propargyl alcohols under Brønsted acid mediation. The methyl (sp(3)-C) group present in the propargyl alcohol becomes a part of a six-membered ring in the final ring-expansion products, the cyclopenta[c]quinolines which are fluorescence active. Based on these observations, a novel one-pot strategy for ring expansion from indole to cyclopenta[c]quinoline is discovered.

Reaction of Indole‐2‐Carboxylates/Carboxylic Acids with Propargylic Alcohols: Dearomative Ring Expansion/Spirocyclization vs Fused Pentacyclics

“…and later by Swamy et al [5a–c] . This product undergoes a novel ring enlargement reaction under [Cu]‐catalyzed conditions to give the cyclopenta[c]quinolines (Scheme 1a); a one pot reaction by sequential addition of PTSA and Cu(OTf) 2 is also possible [5c] . Indole 2‐carboxylates react with tertiary propargyl alcohols in the presence of PTSA to afford 3‐indenylindoles via allenyl indole intermediates as shown by our group [5d] .…”

“…Under PTSA mediated conditions, if the propargylic side contains a methyl group, the 1,3‐butadienyl substituted indole product can be isolated as shown by Sanz et al . and later by Swamy et al [5a–c] . This product undergoes a novel ring enlargement reaction under [Cu]‐catalyzed conditions to give the cyclopenta[c]quinolines (Scheme 1a); a one pot reaction by sequential addition of PTSA and Cu(OTf) 2 is also possible [5c] .…”

Regioselective Direct C‐Alkenylation of Indoles

“…Brønsteda cids are poorly effective on simple alkynes but give satisfactory resultsw ith functionalized reactants leading to stabilized carbocationic intermediates such as propargyl alcohols (Scheme 31). [85] In this process, excesso fp-toluenesulfonic acid promotes the dehydration of the propargyl alcohol leadingt oc ationic intermediate 19 which regioselectively reacts with the indole leading to an allenylindole intermediate. [86] The final products are the result of a1 ,3-proton shift which generates the stable dienyli ndole derivatives.…”

Recent Advances in Direct Catalytic Dehydrative Substitution of Alcohols

“…In one pot, alcohol activation was catalyzed by p-toluenesulfonic acid, followed by a postulated Cu(II)-catalyzed spirocyclization and oxidative ring-expansion. 97 Another interesting study was reported by Li and co-workers, who opted to investigate the gold-catalyzed dehydrative substitution of propargylic alcohols (Scheme 6). Using Au(III) precatalyst 1 and AgSbF 6 as a co-catalyst, nucleophilic addition of a range of typical arenes was found to occur at the distal C3-position to generate a series of trisubstituted allenes.…”