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Synthesis of 1-(4-bromophenyl)-2-(thiophen-3-yl)ethane-1,2-dione through 2-oxoiminium mediated oxidative cross coupling reaction; 1-(4-Bromophenyl)-2-(thiophen-3-yl)ethane-1,2-dione

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Submitted Jan 15, 2021, published Feb 22, 2021
Satyanarayana Battula (satyamssd@gmail.com), Bhavyesh Desai (bhavyeshdesai42@gmail.com)
A contribution from Satyam's Group
Reaction Scheme: Synthesis of 1-(4-bromophenyl)-2-(thiophen-3-yl)ethane-1,2-dione through 2-oxoiminium mediated oxidative cross coupling<strong> </strong>reaction

Chemicals Used

1. (4-bromophenyl)boronic acid (Sigma-Aldrich), ( 95.0%), B75956

2. 2-Oxo-2-(thiophene-3-yl)acetaldehyde (Synthesized from 3-acetylthiophene,1 Sigma-Aldrich, 98%, 196320)

3. Pyrrolidine (Sigma-Aldrich), (99%), P73803

4. Toluene (Rankem), directly used without drying

5. Ethyl acetate (SD Fine Chemicals Ltd), directly used without drying

6. Hexane (SD Fine Chemicals Ltd), directly used without drying

Procedure

Reaction vessel was charged with 2-oxo-2-(thiophene-3-yl)acetaldehyde (105 mg, 0.746 mmol) and (4-bromophenyl)boronic acid (179 mg, 0.895 mmol)  and pyrrolidine (13 µL, 20 mol%) in 2 mL toluene solvent. This reaction mixture was allowed to stir at 80oC for 4 h. The progress of the reaction was monitored by TLC, after completion of the reaction, excess solvent was removed under vaccum using rotavapor. The crude reaction mixture was extracted in EtOAc from its aqueous workup. The organic portion in EtOAc was concentrated under vaccum and was purified by column chromatography using silica gel (100-200 #) with ethyl acetate and hexane (1:10) as an eluent. Yield of the desired product is 94% and obtained as yellow solid.

Author's Comments

  • Initially 2-Oxo-2-(thiophene-3-yl)acetaldehyde reacts with pyrrolidine to form 2-oxoiminium ion which can differentiate the regular iminium in the reactivity.
  • Carbonyl group in 2-oxoimminium ion increases its reactivity, and thus undergoes nucleophilic [1,2] addition of boronic acid followed by in situ abstraction of proton (boric acid), deamination and aerobic oxidation to form the final dione product.
  • α-Ketoamide is formed in the absence of boronic acid nucleophile.
  • Generally, this sort of coupling reaction requires harsh reaction conditions.

Data

1H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 2.8, 1.2 Hz, 1H), 7.93 – 7.83 (m, 2H), 7.70 – 7.62 (m, 3H), 7.41 (dd, J = 5.1, 2.9 Hz, 1H);

13C NMR (126 MHz, CDCl3) δ 191.91, 186.39, 137.74, 137.34, 137.25, 132.31, 131.50, 130.42, 127.33, 127.15

GC-MS (EI) m\z (relative intensity): 294.0 (M+, 2.6), 183.1 (25), 155.2 (11), 111.2 (100), 83.0 (8.4).

Lead Reference

N. Mupparapu, N. Battini, S. Battula, S. Khan, R. A. Vishwakarma, Q. N. Ahmed, Aminocatalytic Cross-Coupling Approach via Iminium Ions to different C-C Bonds. Chem. Eur. J. 2015, 21, 2954-2960

DOI: https://doi.org/10.1002/chem.201405477.

Other References

  1. Riley, H. A.; Gray, A. R. Org. Synth. Coll. 1935, 15, 67.
  2. M. Wasa, R. Y. Liu, S. P. Roche, E. N. Jacobsen, J. Am. Chem. Soc. 2014, 136, 12872-2875.

https://doi.org/10.1021/ja5075163

  1. G. D. Vo, J. F. Hartwig, J. Am. Chem. Soc. 2009, 131, 11049-11061.

https://doi.org/10.1021/ja903049z

  1. L. Huang, K. Cheng, B. Yao, Y. Xie, Y. Zhang, J. Org. Chem. 2011, 76, 5732 –5737

https://doi.org/10.1038/nchem.862

Supplementary Information

e.g. Actual NMR spectra (as images or jdx files for interactive spectra), photographs of apparatus, TLC’s or crystals or videos. Please contact the ChemSpider team (ChemSpider-at-rsc.org) for help with this.
Data.docx

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Keywords: 2-oxoiminium ion, aldehydes, amines, dione, heterocyclic compounds, nucleophilic, oxidative addition, thermal