Copper Catalysis for Nicotinate Synthesis through β‐Alkenylation/Cyclization of Saturated Ketones with β‐Enamino Esters

Abstract

The first example of a Cu-catalyzed and 4-OH-TEMPO mediated intermolecular [3 + 3] annulation of saturated ketones with b-enamino esters is reported herein, which was successfully used for the synthesis of versatile nicotinates through sequential b-C(sp 3 )-H bond alkenylation, enaminecarbonyl condensation and aromatization. This protocol tolerates a variety of functional groups, thereby providing a practical and efficient method for the fabrication of 5H-chromeno[4,3-b]pyridin-5one skeletons.

Syntheses of N-Alkyl 2-Arylindoles from Saturated Ketones and 2-Arylethynylanilines via Cu-Catalyzed Sequential Dehydrogenation/Aza-Michael Addition/Annulation Cascade

“…Based on the control experiments and previous work on Cu-catalyzed activation of saturated ketones, − the proposed mechanism is depicted in Scheme applying 2-(phenylethynyl)­aniline ( 1a ) and propiophenone ( 2a ) as template substrates. Initially, 2a was transformed into enone A through a Cu-catalyzed oxidative dehydrogenation reaction, followed by the copper-promoted nucleophilic attack of 1a to form the key intermediate C .…”

“…In 2016, Su’s group reported the first example of a Cu-catalyzed dehydrogenation–conjugate addition tandem reaction for the direct β-functionalization of inactivated ketones with various nucleophiles . Inspired by this fantastic work, the research community has devoted much attention to the Cu-catalyzed one-pot cascade reactions for synthesizing versatile N-heterocycles, including pyrimidines, pyrazoles, quinolines, pyridines, and isoindolin-1-ones . However, the construction of indole rings through β-C­(sp 3 )-H functionalization of saturated ketones remains an unexploited field.…”

Continuous-Flow Synthesis of β-Amino Acid Esters by Lipase-Catalyzed Michael Addition of Aromatic Amines

“…β-Amino acid ester derivatives have been widely found in biologically active molecules, many of which possess useful biological activities (e.g., anticancer, antiviral, antibacterial, antifungal, antipsychotics) [1][2][3][4][5][6]. β-Amino acid esters have also been used to construct peptidomimetic oligomers, which are of high interest in medicinal chemistry [7,8].…”

Divergent Synthesis of Multisubstituted Unsymmetric Pyrroles and Pyrrolin‐4‐ones from Enamino Esters via Copper‐Catalyzed Aerobic Dimerization

“…Meanwhile, enamino ester is an essential and widely applicable chemical synthon in organic chemistry. Furthermore, it could easily undergo radical reactions to construct heterocyclic derivatives . For example, Guan and co‐workers have recently demonstrated that K 2 S 2 O 8 ‐promoted oxidative cyclization of enamines provided a variety of pyrroles.…”

“…In our previous work, we have developed the synthetic route for functionalized quinolines from enamino esters and ortho‐halogenated aromatic carbonyl compounds via the copper‐catalyzed tandem reaction (Scheme c). [5c] During the course of our research program on copper‐catalyzed aerobic oxygenation/oxidation reactions, we became interested in the synthesis of multisubstituted unsymmetric pyrroles. Herein we report an additive‐induced highly divergent synthesis of multisubstituted pyrroles and pyrrolin‐4‐ones from enamino esters through copper‐catalyzed oxidative cyclization and 1,2‐aryl migration.…”