Auto‐Oxidative Povarov/Aromatization Tandem Reaction of Glycine Derivatives with Enamides: Acylamino as both Activating and Leaving Group

Abstract

The auto-oxidative Povarov/aromatization tandem reaction of N-aryl glycine derivatives with enamides yields a series of complex quinoline derivatives in good yields. The reactions are performed using only catalytic amount of Brønsted acid and O 2 . The acylamino group is used as both activating and leaving group to improve the reaction efficiency in this transformation.

The Povarov Reaction: A Versatile Method to Synthesize Tetrahydroquinolines, Quinolines and Julolidines

“…1,8 When no oxidizing agent is added to the reaction medium, O 2 (air) is the final oxidant. 14,136 Similarly to the synthesis of THQs, these reactions can be catalyzed by Lewis and Brønsted acids such as BF 3 •OEt 2 , 36,40,137-142 BF 3 •O(CH 3 ) 2 , 143,144 FeCl 3 , 145,146 InCl 3 , 147 trifluoromethanesulfonic acid, 148 p-toluenesulfonic acid, 146 CX4SO 3 H, 14,149 TFA, 150,151 camphorsulfonic acid, 152 tris(4-bromophenyl)aminium (TBPA + ), 140,[153][154][155] CBr 4 , 156 iron, 157 copper iodide 158 and iodine. [159][160][161][162][163][164][165][166][167] Furthermore, different triflates have been widely used such as Sc(OTf) 3 , 154,168,169 Yb(OTf) 3 , [170][171][172][173] Cu(OTf) 2 , 174,175 Ce(OTf) 3 , 176,177 Zn(OTf) 2 , 178 AgOTf, 22 In(OTf) 3 179 and Ca(OTf) 2 .…”

“…Regarding the reaction medium, various polar and nonpolar solvents have been explored, for example, acetonitrile, 2,4,6,[22][23][24][36][37][38] THF, 159,161 DMSO, 160,162,163,166,173 ethanol, 146,[181][182][183] DMF, 158 acetic acid, 157 dichloromethane, 97,138,145,148,150,179,180,184 TFE, 137,152 diethyl ether, 185 dichloroethane, 140,142,151,153,165,186 chloroform 174 and toluene. 147,171,177 Greener alternatives were also reported such as the absence of a solvent 84,149,174,176,178 or the use of a DES (Scheme 13).…”

Photocatalyzed Reverse Polarity Oxidative Povarov Reaction of Glycine Derivatives with Maleimides

“…[ 7 ] Since then, the oxidative Povarov reaction/aromatization tandem process of N ‐aryl glycine derivatives with electron‐rich olefins to form quinoline‐2‐carboxylates has been extensively studied (Scheme 2, B). [ 8 ] Pyrrolo[3,4‐c]quinoline‐1,3‐diones are an important class of heteroaromatic structures with promising bio‐ activities. [ 9 ] They have been reported as anti‐tumor agents, central nervous system active agents, and caspase‐3 inhibitors.…”