Single‐Step Synthesis of 3‐Iodoquinolines from 2‐Aminophenyl Ketones through a Regioselective (6‐endo‐dig) Electrophilic Cyclization

Abstract

A highly facile single‐step synthetic approach to 3‐iodoquinolines has been developed for the first time from readily available 2‐aminobenzophenones and terminal alkynes. The reaction involves the nucleophilic addition of terminal alkynes to 2‐aminobenzophenones followed by a regioselective iodocyclization (6‐endo‐dig) to furnish 2,4‐disubstituted 3‐iodoquinolines in high yields. In general, 2,4‐diaryl‐substituted products were isolated without the need for column chromatography.

Electrophilic Cyclization of 2‐Aminophenylprop‐1‐yn‐3‐ols into 3‐Iodo‐6‐(aryldiazenyl)quinolines by Using a One‐Pot Azo‐Coupling and Iodocyclization Sequence

“…Synthesis of Ethyl ( E )‐3‐{6‐[( E )‐(4‐Nitrophenyl)diazenyl]‐4‐phenyl‐2‐( p ‐tolyl)quinolin‐3‐yl}acrylate (6): Ethyl acrylate (47 mg, 0.47 mmol) was added to a solution of ( E )‐3‐iodo‐6‐[(4‐nitrophenyl)diazenyl]‐4‐phenyl‐2‐( p ‐tolyl)quinoline ( 3j , 115 mg, 0.23 mmol) in DMF (1.8 mL) that contained K 2 CO 3 (53 mg, 2.5 equiv.) and Bu 4 NBr (50 mg, 1 equiv.).…”

“…General Experimental Procedure for the Synthesis of ( E )‐6‐[(4‐Nitrophenyl)diazenyl]‐4‐phenyl‐3‐(phenylethynyl)‐2‐( p ‐tolyl)quinoline (7): Pd(OAc) 2 (2 mol‐%) was dissolved in MeCN (1 mL), and then the indicated amount of a Pd(OAc) 2 /acetonitrile solution was added to a mixture of the alkyne (44.5 mg, 0.45 mmol), aryl halide 3j (115 mg, 0.22 mmol), DABCO (76 mg, 3 equiv. ), and MeCN (4 mL).…”

“…General Experimental Procedure for the Synthesis of ( E )‐6‐[(4‐Nitrophenyl)diazenyl]‐3,4‐diphenyl‐2‐( p ‐tolyl)quinoline (8): PhB(OH) 2 (41.1 mg, 0.33 mmol) was added to a solution of ( E )‐3‐iodo‐6‐[(4‐nitrophenyl)diazenyl]‐4‐phenyl‐2‐( p ‐tolyl)quinoline ( 3j , 140 mg, 0.27 mmol) in DMF/H 2 O (2:1, 3.0 mL) that contained Na 2 CO 3 (27.4 mg, 1 equiv.). The resulting mixture was stirred at room temperature for 5 min.…”

“…Recently, we reported a technically valuable method for the scalable one‐pot synthesis of 3‐iodoquinolines from readily available 2‐arylamino ketones and terminal alkynes . In continuation of our research interests in the synthesis of quinoline derivatives and electrophilic cyclizations, we herein report the first one‐pot synthesis of 6‐(aryldiazenyl)‐3‐iodoquinolines by starting from 2‐aminoaryl propargyl alcohols , …”

“…Most of these electrophilic cyclization strategies involve the interaction of an electrophilic reagent with an unsaturated C–C bond followed by the intramolecular addition of a N‐nucleophile (azacyclization) to give the privileged quinoline scaffold (Scheme ). For example, propargyl alcohol 1 has been treated with electrophilic iodine under various conditions to afford a series of 3‐iodoquinolines . Stein et al reported the synthesis of 3‐organoseleno‐substituted quinolines by carrying out the electrophilic cyclization of 1 with 1.5 equiv.…”