Copper‐Catalyzed [3+2] Annulation of 2‐Arylidene‐1,3‐Indandiones with N‐Acetyl Enamides for the Synthesis of Spiropyrrolines

Abstract

A copper-catalyzed intermolecular [3 + 2] annulation of 2-arylidene-1,3-indandiones with N-acetyl enamides has been developed to assemble spirocyclic pyrrolines, which are important building blocks for organic synthesis and drug discovery. This heteroannulation protocol tolerates various functional groups and proceeds in good to excellent yields. Mechanistic studies reveal that the reactions might involve radical processes.

Additive‐Free Synthesis of Trifluoromethylated Spiro Cyclopropanes and Their Transformation into Trifluoromethylated Building Blocks

“…It is worth mentioning in this context that spiropyrrolines constitute an ubiquitous class of spirocyclic scaffolds with immense bioactivity and excellent therapeutic profile. [15] Next, the substrate scope was evaluated using various arylnitriles. To our delight, the substituents such as methoxy, methyl, and bromo at the 4-position of benzonitrile were well tolerated to afford the corresponding spiro-pyrrolines in good to excellent yields (5 b-5 d).…”

Indane-1,3-Dione: From Synthetic Strategies to Applications

“…Copper was also used as a catalyst for the synthesis of spiro compounds. In a [3+2] radical cycloaddition catalyzed by copper, 2-arylidene-indane-1,3-dione 255 could react in the presence of N-acetyl enamides 464 at high temperature [305]. Many N-acetyl enamides 464 and 2-arylidene-indane-1,3-diones 255 were mixed, providing a wide range of spiro structures 465 (see Table 35 and Scheme 144).…”

“…Mechanism involved in the copper-catalyzed synthesis of spiro compounds. Reproduced with permission from Ref [305]…”

A Three-Component Synthesis of Spiropyrrolines

“…20 Similarly, Guo and coworkers utilized copper(I)-catalyzed annulation of 2-arylidene-1,3-indandiones and ketoximes (Scheme 1c) in 2020. 21 Rawat and the group also employed the same starting materials to prepare spiropyrrolines by using different copper catalysts. 22 Surprisingly, all these existing reports utilized a prefunctionalized common starting material, 2-arylideneindane-1,3-dione (5), in the presence of copper(I) as an inevitable common catalyst.…”

“…Later on, Wei and co-workers established copper­(I)-catalyzed intermolecular cyclization between 2-arylideneindane-1,3-dione and N -acetyl enamides (Scheme b) in 2017 . Similarly, Guo and co-workers utilized copper­(I)-catalyzed annulation of 2-arylidene-1,3-indandiones and ketoximes (Scheme c) in 2020 . Rawat and the group also employed the same starting materials to prepare spiropyrrolines by using different copper catalysts .…”