Synthesis of Spiroindenyl-2-Oxindoles through Palladium-Catalyzed Spirocyclization of 2-Bromoarylamides and Vinyl Bromides
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimization of the Reaction Conditions
2.2. Substrate Scope for Acrylamides
2.3. Substrate Scope for Vinyl Bromides
2.4. Mechanistic Studies
3. Materials and Methods
3.1. General Information
3.2. Experimental Procedures
- (a)
- A 25 mL Schlenk-type tube (with a Teflon screw cap and a side arm) equipped with a magnetic stir bar was charged with Pd(OAc)2 (0.02 mmol, 4.4 mg, 0.1 equiv), s-phos (0.02 mmol, 8.2 mg, 0.1 equiv), K2CO3 (1.2 mmol, 165.9 mg, 6.0 equiv), 18-crown-6 (0.4 mmol, 105.7 mg, 2.0 equiv), acrylamide 1a (0.2 mmol, 63.2 mg, 1.0 equiv), 1-bromo-1-propene 2a (0.8 mmol, 96.8 mg, 4.0 equiv), and THF (2.0 mL). The reaction mixture was frozen with liquid nitrogen, and then, the tube was evacuated and backfilled with nitrogen (6 times). The reaction tube was put into an oil bath and then heated to 100 °C. The reaction mixture was stirred at 100 °C for 24 h. After being cooled down to room temperature, the reaction mixture was diluted with EtOAc (15 mL), washed with brine (3 times), dried over Na2SO4, and concentrated in vacuo. The residue was purified by preparative silica gel TLC with petroleum ether/ethyl acetate (ether/ethyl acetate 25:1) to afford 3aa (71%, 39.0 mg).
- (b)
- A 25 mL Schlenk-type tube (with a Teflon screw cap and a side arm) equipped with a magnetic stir bar was charged with Pd(OAc)2 (0.02 mmol, 4.4 mg, 0.1 equiv), s-phos (0.04 mmol, 16.4 mg, 0.2 equiv) K2CO3 (1.0 mmol, 138.2 mg, 5.0 equiv), 18-crown-6 (0.4 mmol, 105.7 mg, 2.0 equiv), acrylamide 1a (0.2 mmol, 63.2 mg, 1.0 equiv), β-bromostyrene 2b (0.6 mmol, 109.8 mg, 3.0 equiv), and THF (2.0 mL). The reaction mixture was frozen with liquid nitrogen and then the tube was evacuated and backfilled with nitrogen (6 times). The reaction tube was put into an oil bath and then heated to 130 °C. The reaction mixture was stirred at 130 °C for 24 h. After being cooled down to room temperature, the reaction mixture was diluted with EtOAc (15 mL), washed with brine (3 times), dried over Na2SO4, and concentrated in vacuo. The residue was purified by preparative silica gel TLC with petroleum ether/ethyl acetate (ether/ethyl acetate 25:1) to afford 3ab (61%, 41.2 mg) and 3ab-l (34%, 22.9 mg).
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
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Entry | Variation from the Standard Conditions | Yield a |
---|---|---|
1 | No | 74% (71% b) |
2 | No 18-crown-6 | 55% |
3 | No s-phos | 18% |
4 | x-phos instead of s-phos | 53% |
5 | Ru-phos instead of s-phos | 62% |
6 | (o-tolyl)3P instead of s-phos | 60% |
7 | Ph3P instead of s-phos | 63% |
8 | Na2CO3 instead of K2CO3 | 5% |
9 | KOAc instead of K2CO3 | 3% |
10 | DMF instead of THF | 43% |
11 | toluene instead of THF | 59% |
12 | CH3CN instead of THF | 14% |
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Yang, S.; Zhang, Y. Synthesis of Spiroindenyl-2-Oxindoles through Palladium-Catalyzed Spirocyclization of 2-Bromoarylamides and Vinyl Bromides. Molecules 2021, 26, 7496. https://doi.org/10.3390/molecules26247496
Yang S, Zhang Y. Synthesis of Spiroindenyl-2-Oxindoles through Palladium-Catalyzed Spirocyclization of 2-Bromoarylamides and Vinyl Bromides. Molecules. 2021; 26(24):7496. https://doi.org/10.3390/molecules26247496
Chicago/Turabian StyleYang, Shuai, and Yanghui Zhang. 2021. "Synthesis of Spiroindenyl-2-Oxindoles through Palladium-Catalyzed Spirocyclization of 2-Bromoarylamides and Vinyl Bromides" Molecules 26, no. 24: 7496. https://doi.org/10.3390/molecules26247496