Metal-Free Synthesis of 2-Benzylideneindolin-3-ones via a Nucleophilic/Rearrangement/Azide–Alkene Cascade Reaction

Quan Tang; Sheng-Chao Huang; Hua Wang; Tianyu Long; Han-Han Kong; Qing-Qing Yang; Nianyu Huang; Long Wang

doi:10.1055/a-2341-9185

Synlett, Table of Contents

Synlett 2025; 36(04): 341-346
DOI: 10.1055/a-2341-9185

letter

Metal-Free Synthesis of 2-Benzylideneindolin-3-ones via a Nucleophilic/Rearrangement/Azide–Alkene Cascade Reaction

Authors

Quan Tang‡

^aCollege of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, Hubei 443002, P. R. of China
Sheng-Chao Huang‡

^dHubei Three Gorges Laboratory, Yichang, Hubei 443007, P. R. of China
Hua Wang‡

^aCollege of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, Hubei 443002, P. R. of China
Tianyu Long‡

^aCollege of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, Hubei 443002, P. R. of China

^bCollege of Hydraulic and Environmental Engineering, China Three Gorges University, Yichang, Hubei 443002, P. R. of China
Han-Han Kong ∗

^aCollege of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, Hubei 443002, P. R. of China
Qing-Qing Yang

^aCollege of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, Hubei 443002, P. R. of China
Nianyu Huang

^cHubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Science, China Three Gorges University, Yichang, Hubei 443002, P. R. of China
Long Wang ∗

^aCollege of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, Hubei 443002, P. R. of China

^dHubei Three Gorges Laboratory, Yichang, Hubei 443007, P. R. of China

Abstract

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Abstract

A metal-free synthesis of 2-benzylideneindolin-3-ones through a formal [4+1] annulation from o-azidobenzaldehydes and terminal alkynes has been developed. The method features operational simplicity, mild reaction conditions, and ready availability of starting materials. A broad range of 2-benzylideneindolin-3-ones were prepared in moderate to excellent yields. Mechanistic studies indicated that the reaction might proceed through a nucleophilic addition/rearrangement/azide–alkene cycloaddition pathway to produce 2-benzylideneindolin-3-ones.

Key words

metal-free synthesis - benzylideneindolinones - azidobenzaldehydes - terminal alkynes - azide–alkene cycloaddition - cascade reaction

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References

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19 2-Benzylideneindolin-3-one^5b (3a); Typical Procedure A round-bottomed flask equipped with a stirrer bar was sequentially charged with o-azidobenzaldehyde (1a; 0.5 mmol, 1.0 equiv), DMSO (5.0 mL), phenylacetylene (2a; 0.75 mmol, 1.5 equiv), and 50 wt% aq Bu₄NOH (0.8 mmol, 1.6 equiv). The mixture was stirred at r.t. under air until the reaction was complete (TLC). The reaction was then quenched with H₂O, and the mixture was extracted with EtOAc. The combined organic layers were dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (silica gel) to give an orange solid; yield: 88 mg (79%); mp 189.8–191.0 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.74 (d, J = 7.7 Hz, 1 H), 7.55 (d, J = 7.4 Hz, 2 H), 7.49–7.41 (m, 3 H), 7.32 (t, J = 7.4 Hz, 1 H), 6.98 (dt, J = 14.9, 8.2 Hz, 3 H), 6.86 (s, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 186.82, 153.39, 136.33, 135.49, 134.84, 129.66, 129.32, 128.66, 125.16, 121.80, 120.77, 112.14, 111.80.

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