A New One-Pot Synthesis of Quinoline-2-carboxylates under Heterogeneous Conditions

Abstract

Quinoline-2-carboxylates are an important subclass of quinoline derivatives largely present in a variety of biologically active molecules, as well as useful ligands in metal-catalyzed reactions. Herein, we present a new one-pot protocol for synthesizing this class of derivatives starting from β-nitroacrylates and 2-aminobenzaldehydes. In order to optimize the protocol, we investigated several reaction conditions, obtaining the best results using the 2-tert-Butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) as solid base, in acetonitrile. Finally, we demonstrated the generality of our approach over several substrates which led to synthesize a plethora of functionalized quinolines-2-carboxylate derivatives in good overall yields.

β-Nitroacrylates: New Key Precursors of Indole-2-Carboxylates via Fischer Indole Synthesis

“…Among them, α-ketoesters are of particular interest since they are key precursors of alkyl indole-2-carboxylates, a very important class of indole that is widely investigated for its activities and is exploited as a strategic intermediate of biologically active targets, such as the NNRTI Delavirdine and its analogues [12][13][14][15][16][17]. Recently, following our study concerning the use of β-nitroacrylates 1 as a useful building block of heterocyclic systems [18][19][20][21], we reported a new protocol for synthesizing 5, starting from 1 and o-bromoanilines, based on a palladium catalyzed Heck coupling [22] (Scheme 3, Way b). Now, in continuing this study with the aim of avoiding the use of precious metal (Pd), we found 1 to be a valuable alternative of α-ketoesters for the Fischer indole synthesis (Scheme 3, Way a).…”

β‐Nitroacrylates: A Versatile and Growing Class of Functionalized Nitroalkenes

“…Recently, β‐nitroacrylates 1 were successfully used, in combination with ortho ‐aminobenzaldehydes 59 , for the preparation of polysubstituted quinoline‐2‐carboxylates 61 (Scheme ) …”

Repurposing an Aldolase for the Chemoenzymatic Synthesis of Substituted Quinolines

“…The scope of the reaction was limited to arylalkynes and to anilines bearing an electron-donating group in the para position. Gabrielli et al reported a one-pot aza-Michael–Henry reaction using a polystyrene-bound phosphazene base (Figure b), although the yields did not exceed 64% . Most recently, Wang et al reported a photocatalytic approach to quinaldic esters in moderate to good yields (Figure c) .…”

“…Recent quinaldic acid forming reactions: (a) tandem synthesis of quinaldic esters; (b) aza-Michael–Henry reaction; (c) aerobic oxidative dehydrogenative coupling; (d) the NahE-catalyzed reaction reported here.…”