Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Scheme 1

Control experiments.

The ubiquitous oxazoles have attracted more and more attention in both industrial and academic fields for decades. This interest arises from the fact that a variety of natural and synthetic compounds which contain the oxazole substructure exhibit significant biological activities and antiviral properties. Although various synthetic methodologies for synthesis of oxazols have been reported, the development of milder and more general procedure to access oxazoles is still desirable.

Initially, compound A, formed by the substitution reaction of 1a with 2a, which can be transformed following two pathways: (a) I+, generated by the oxidation of iodine, could oxidize A to radical intermediate B, which eliminates one molecular of CO2 to generate radical C, which is further oxidized to imine Dor its isomer E. Subsequently, F is obtained by intramolecular nucleophilic addition of E. Finally, the desired product (3a) is given by deprotonation and oxidation of F; (b) G is formed from the oxidation of A. Then 3a is obtained through H, I, J, K following a process similar to path a.

Scheme 2

Plausible mechanism.

General procedure for the synthesis of polysubstituted oxazoles

1a (105.8 mg, 0.7 mmol), 2a (99.5 mg, 0.5 mmol), I2 (50.8 mg, 0.2 mmol), DMA (2 mL) and TBHP (70% aqueous solution, 1 mmol) were placed in a tube (10 mL) and sealed with a thin film. Then the reaction mixture was stirred at 25°C for 4 h, heated up to 60°C and stirred at this temperature for another 4 h. After that, the resulting mixture was cooled to the room temperature, diluted with water, extracted with ethyl acetate. The organic phase was washed with saturation sodium chloride solution, dried and filtrated. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column separation (petroleum ether:ethyl acetate = 10:1) to give 3a(154.7 mg, 70%) as light yellow solid, mp = 70–72°C.

2,5-diphenyloxazole (3a) [1]

Synthesized according to typical procedure and purified by column chromatography (petroleum ether:ethyl acetate = 10:1) to give light yellow solid (154.7 mg, 70%), mp = 70-72 °C.

1H NMR (300 MHz, CDCl3): δ 8.12-8.09 (m, 2 H), 7.72-7.69 (m, 2 H), 7.50-7.40 (m, 6 H), 7.35-7.24 (m, 1 H).

13C NMR (75 MHz, CDCl3): δ 161.3, 151.4, 130.4, 129.0, 128.9, 128.5, 128.1, 127.6, 126.4, 124.3, 123.6.

HRMS (APCI-FTMS) m/z: [M + H]+ calcd for C15H12NO: 222.0913, Found: 222.0911.

D1 D2

The scope of the reaction. Standard conditions: 0.7 mmol of amino acids (1a1h), 0.5 mmol of2a2j, 0.1 mmol of I2, 1 mmol of TBHP, 2 mL of DMA, were stirred at 25°C for 4 h then slowly raised to 60°C for 4 h. Catalysts amount and isolated yields were based on 2.

Metal-free synthesis of polysubstituted oxazoles via a decarboxylative cyclization from primary α-amino acids

Yunfeng Li, Fengfeng Guo, Zhenggen Zha and Zhiyong Wang*

Zhiyong Wang

Department of Chemistry, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China

Sustainable Chemical Processes 2013, 1:8  doi:10.1186/2043-7129-1-8

The electronic version of this article is the complete one and can be found online at:http://www.sustainablechemicalprocesses.com/content/1/1/8

ADDITIONAL SPECTRAL DATA FROM NET

WANG Zhiyong(汪志勇)


Ph.D., University of Science and Technology of China (USTC) (1992); M.S., USTC (1989); B.S., Anhui Normal University (1982).

Professor of Chemistry
Department of Chemistry
School of Chemistry and Materials Science
University of Science and Technology of China
Hefei, Anhui 230026, P. R. China

Tel: 86-551-63603185
Fax: 86-551-63603185
E-mail: zwang3@ustc.edu.cn
Personal Homepage:
http://staff.ustc.edu.cn/~zwang3/default.htm

  • RESEARCH INTERESTS
    Research in our group will focus on the general areas of reaction development and chemical synthesis. Our studies will be driven by the discovery of new and useful catalysts. By virtue of the developed organic reactions various organic ligands are synthesized and used as probes in biological progress. Brief summaries of three research directions illustrating these objectives are shown below:
    1) The preparation of heterogeneous catalysts;
    2) The theoretical calculation for the mechanism of organic reactions;
    The application of organic ligands as probes or inhibitors to explore the molecular mechanism of HIV transcription.

    PUBLICATIONS
    http://www.researcherid.com/rid/F-7955-2010

    WANG Zhiyong, Professor
    Name: Zhiyong Wang(汪志勇)
    Born: June, 1962, Anhui, P. R. China
    Address: Department of Chemistry, University of Science and Technology of China, 230026 Hefei, P. R. China
    Tel: 86-551-63603185
    Fax: 86-551-63603185
    E-mail: zwang3@ustc.edu.cn
    EDUCATION AND RESEARCH EXPERIENCE
     1978-1982 B.S., Anhui Normal University
     1982-1986 Lecturer, South Anhui Agricultural College, China
     1986-1989 M.S., University of Science and Technology of China
     1989-1992 Ph.D., University of Science and Technology of China
     1992-1997 Lecturer, Associate Professor, University of Science and Technology of China
     1997-1999 Research Fellow, Tulane University & Brandeis University
     1999-Now Professor of Chemistry, University of Science and Technology of China
    RESEARCH INTERESTS
    1) Organic reactions in aqueous media and development of synthetic methodology;
    2) Supramolecular assembly under the control of organic ligands;
    3) Drug design on the base of PCAF bromodomain.
    CURRENT RESEARCH PROJECTS
    1) Organic reactions in water mediated by nano-metals and its application in asymmetric synthesis, National Natural Science Foundation (2004-2006)
    2) Crystal Engineering under control of organic ligands, Foundation from Education Department of Anhui Province (2003-2005)
    REPRESENTATIVE PUBLICATIONS
    1) C-F. Pan, M. Meze, S. Mujtaba, M. Muller, L. Zeng, J-M. Li, Z-Y. Wang,* M-M. Zhou*
    “Structure-Guided Optimization of Small Molecules Selectively Inhibiting HIV-1 Tat and PCAF Association” J. Med. Chem., 2007, 50, 2285
    2) Y. Xie, Z-P. Yu, X-Y. Huang, Z-Y. Wang,* L-W. Niu, M-K. Teng, J. Li
    “Rational Design on the MOFs Constructed from modified Aromatic Amino Acids”
    Chem. Eur. J., 2007, 13, 9399
    3) Z-H. Zhang, C-F. Pan, Z-Y. Wang* “Synthesis of chromanones: a novel palladium-catalyzed Wacker-type oxidative cyclization involving 1,5-hydride alkyl to palladium migration” Chem. Commun, 2007, 4686
    4) Y. Xie, Y. Yan, H-H. Wu, G-P. Yong, Y. Cui, Z-Y. Wang*, L. Pan, J. Li “Homochiral Metal-organic Coordination Networks from L-Tryptophan” Inorg. Chim. Acta., 2007, 360,1669
    5) Y. Xie, H-H. Wu, G-P. Yong,, Z-Y. Wang*, R. Fan , R-P. Li, G-Q. Pan, Y-C. Tian, L-S. Sheng, L. Pan, J. Li “Synthesis, Crystal Structure, Spectroscopic and Magnetic Properties of Two Cobalt Molecules Constructed from Histidine” J. Mol. Struct., 2007, 833, 88
    6) Z-H. Zhang, Z-Y. Wang* “Diatomite-Supported Pd Nanoparticles: An Efficient Catalyst for Heck and Suzuki Reactions” J. Org. Chem., 2006, 71, 7485
    7) Z-H. Zhang, Z-G. Zha, C-S. Gan, C-F. Pan, Y-Q. Zhou, Z-Y. Wang*, M-M. Zhou* “Catalysis and Regioselectivity of the Aqueous Heck Reaction by Pd(0) Nanoparticles under Ultrasonic Irradiation”
    J. Org. Chem., 2006, 71, 4339

Hefei, Anhui China

////Metal-free,  Synthesis,  Oxazoles, Oxidation,  Decarboxylative cyclization,  α-amino acids

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