Gold‐Catalyzed Annulation of Ynamides with Aminocarbonyls as a Route to 2‐Aminoquinolines Diversely Substituted at the 4^th‐Position

Abstract

Gold‐catalyzed interplay between ynamides and aminocarbonyls comprises a route to 2‐aminoquinolines. This modular annulation proceeds under relatively mild conditions (Ph3PAuCl/AgNTf2 5 mol %, DCE, 60–80 °C), and a number of functionalities were compatible (42 examples; 25–98% yields). In contrast to a group of other gold‐catalyzed methods employing the ynamide/amine combinations for the assembly of 2‐aminoquinolines, the developed approach utilizes a diversity of aminocarbonyl substrates and, in particular, allows a variation of the substituents in the 4th quinoline position. The synthetic potential of the obtained heterocyclic products was illustrated by post‐modifications of the quinoline backbone and the peripheral substituents.

Gold catalysis in quinoline synthesis

“…Most recently, a gold-catalyzed annulation of 2-aminocarbonyls with ynamides was reported by Dubovtsev and co-workers. 47 As depicted in Scheme 17, a wide range of 2-aminocarbonyls 50 reacted with ynamides 51 in the presence of 5 mol% PPh 3 AuCl/AgNTf 2 as the catalyst in DCE at 60 °C, leading to the formation of 2-aminoquinolines 52 in 25–98% yields. It should be noted that when less reactive arylketones were used as substrates, a higher reaction temperature of 80 °C and 10 mol% MsOH as an additive were needed to improve the reaction efficiency.…”

TMSOTf-Catalyzed [4 + 2] Annulation of Ynamides and β-(2-Aminophenyl)-α,β-ynones for the Synthesis 2-Aminoquinolines

“…15a,b Recently, Dubovtsev disclosed an elegant assembly of diverse 2-aminoquinolines via a gold-catalyzed annulation of aryl-terminated ynamides with 2-carbonylanilines (Scheme 1d). 16 Despite significant progress, most of these impressive transition-metal-catalyzed routes are applicable only to aryl-terminated ynamides. In 2018, Arcadi's group realized the gold-catalyzed [4 + 2] annulation of oxazolidinone-derived ynamides with β-(2aminophenyl)-α,β-ynones to synthesize 2-aminoquinolines (Scheme 1e).…”

“…Ynamides, as a subclass of nitrogen-atom-substituted alkynes, have attracted considerable attention due to their ability to provide structurally diverse nitrogen-containing heterocycles through transformations such as regioselective difunctionalization and annulation reactions . In recent years, transition-metal-catalyzed annulations of ynamides have offered broad prospects for the efficient generation of 2-aminoquinolines. − In 2016, Hashmi et al described a gold-catalyzed annulation of ynamides with anthranils for the synthesis of 2-aminoquinolines (Scheme a) . In 2018, they achieved the gold-catalyzed [4 + 2] annulation of aryl-terminated ynamides with 2-ethynylanilines to access 4-methyl-2-aminoquinolines (Scheme b) .…”

“…In 2018, they achieved the gold-catalyzed [4 + 2] annulation of aryl-terminated ynamides with 2-ethynylanilines to access 4-methyl-2-aminoquinolines (Scheme b) . Later, Gandon and Liu successively reported the generation of 2,4-diaminoquinolines via the gold- and zinc-catalyzed [4 + 2] annulation of aryl-terminated ynamides with 2-aminobenzonitriles, respectively (Scheme c). , Recently, Dubovtsev disclosed an elegant assembly of diverse 2-aminoquinolines via a gold-catalyzed annulation of aryl-terminated ynamides with 2-carbonylanilines (Scheme d) . Despite significant progress, most of these impressive transition-metal-catalyzed routes are applicable only to aryl-terminated ynamides.…”

Non-Friedländer Route to Diversely 3-Substituted Quinolines through Au(III)-Catalyzed Annulation Involving Electron-Deficient Alkynes

“…Quinoline is one of the most studied heterocycles, − and compounds containing this core are widely represented in natural products, , functional materials, and commercial drugs. , In particular, quinolines bearing sulfonyl substituents at position 3 have recently attracted a significant amount of attention as positron emission tomography radioligands, , agonists of metabotropic glutamate receptor type 5, − and antagonists of the 5-HT 6 receptor; therefore, 3-sulfonylquinolines can be used as promising drugs against different central nervous system disorders and/or diseases, including depression, anxiety, schizophrenia, etc. Structurally related 3-sulfamoylquinolines exhibit anti-breast cancer properties comparable to those of cisplatin.…”