Development of new methodology to the synthesis of symmetrical Biaryls

By Souseelya K Vedula

Faculty Mentor: Dr. Jin Jin

• Introduction• Applications of Biaryls• Results and Discussion• Experimental procedure• Reaction Mechanism• Conclusion• Future work• References

Introduction• Biaryl compounds

• Coupling mechanisms

• Palladium catalyst : Widely used due to its stability to reaction conditions and inertness.

Types of Palladium Catalysts

Homogenous Palladium Catalyst : Palladium is directly added to the reaction mixture which makes the

recovery of the catalyst difficult.

Heterogeneous Palladium Catalyst: Palladium catalyst is attached to a solid support which can be

removed after reaction and can be reused.

Types of Coupling Reactions

Kumada coupling

Buchwald- Hartwig

Hiyama coupling

Applications

• Pharmaceutical Industry- Bi aryl scaffold forms the core of many therapeutic classes such as antifungal, anti-inflammatory, anti rheumatic and

anticancer drugs.

Allocolchicin – tubulin polymerization inhibitor Rhazinilam – tubulin polymerization / depolymerization inhibitor

Baudoin, O., Cesario, M., Guenard, D. J.Org. Chem., 2002, 67, 1199-1207.

Applications

Biphenomycin- A novel peptide

• Agrochemicals • Polymers• Light emitting diodes

Carbonelle, A., Zhu, J. Org. Let., 2000, 2, 3477-3480

Results and Discussionaryl iodide

I

I

I

I

H3CO

I

H2N

I

NH2

I

N

I

TeNH2 NH2

Te

Te

Te

Te

H2N NH2

Te

N

Te

N

Te

H3CO OCH3

entry yieldb (%)

1

product

1a, 92

2 1b, 98

3 1c, 90

4 1e, 82

5 1f, 95

6 1g, 96

7 1h, 56

8 1j, 84

a Reaction conditions: aryl iodide (1 equiv.), Te0 (1 equiv.), KOH (2 equiv.), and DMSO (2 mL) stirred at 110 oC for 10 h under nitrogen. b Isolated yields.

Cl Cl Cl

Table 1: Synthesis of diaryl tellurides

Results and Discussion

Experimental procedure

ArI ArTeArTe0

KOH, DMSO110 oC, 10 h

Scheme 1: Synthesis of symmetrial diaryl telluride ArTeAr

ITe0

KOH, DMSO

1100C, 10H

Te

Experimental procedure

ArTeArPdCl2, Na2CO3

Ar-Ar AgOAc, MeOH, rt 2h

Scheme 2: Synthesis of symmetrical biaryls by detelluration

TePdCl2, Na2CO3

AgOAc,MeOH rt, 2h

Reaction Mechanism

ArTeAr

Ar-Ar

TeAr

ArTe

Ar

ArPd (II)

Te PdAr

Ar

Scheme 3: Proposed mechanism for the formation of symmetrical biaryls

Pd (0) + Te (0) +

Ag+

Pd (II) Pd(0)

Conclusion

• In our research , a new method to synthesize symmetrical bi aryls has been developed by detelluration reaction of symmetrical diaryl tellurides.

• Many biaryls with different functional groups have been synthesized using this new technique.

• The new method to generate the biaryls will lead to more benign alternatives in the field of pharmaceuticals in the synthesis of bi aryl containing drugs.

Future work

• To synthesize more biaryl compounds of different substituents.

• To explore more aspects of organotellurium chemistry.

References• Shin-ichi, K., Puneet, S., Lars, E. Tetrahedron Letters, 2011, 52, 4120-4122.

• Baudoin, O., Cesario, M., Guenard, D. J.Org. Chem., 2002, 67, 1199-1207.

• Carbonelle, A., Zhu, J. Org. Let., 2000, 2, 3477-3480.

• Stille, J.K., Sweet, M.P. Organometallics., 1990, 9, 3189-3191.

• Milstein, D., Stille, J. K. J. Am. Chem. Soc. 1979, 101, 4992–4998.

• Kumada, M., Hayashi, T., Konishi, M., Ito, H. J. Am. Chem. Soc. 1982, 104, 4962–4963.

• Tamao, K., Sumitani, K., Kumada, M. J. Am. Chem. Soc. 1972, 94, 4374-4376.

• Tobrman, T., Juraskova , I., Dvor ak, D. Organometallics. 2014, 33, 6593-6603.

• Najera,C., Gil-Molto, J., Karlstrom,S., Falvello, L.R. Org. Let. 2003, 5, 1451-1454.

• Kaye, S., Fox, J. M.; Hicks, F. A.; Buchwald, S. L. Adv. Synth. Catal. 2001, 343, 789–794.

• Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122, 4020–4028.

• Miyaura, N., Ishiyama, T., Sasaki, H.,Ishikawa, M., Satoh, M., Suzuki, A. J. Am. Chem. Soc. 1989, 111, 314-321.

• Xu, L., Chen, W., Xiao, J. Organometallics 2000, 19, 1123-1127.

• Zhang, L., Qing, J., Yang, P., Wu, J. Org. Let. 2008, 10, 4971-4974.

• Jung, D., Shimogawa, H., Kwon, Y., Mao, Q., Sato, S.I., Kamisuki, S., Kigoshi, H., Uesugi, M. J. Am. Chem. Soc. 2009, 131, 4774-4782.

• Djakovitch, L.; Koehler, K. J. Am. Chem. Soc. 2001, 123, 5990.

• Hatanaka, Y., Hiyama, T. J. Org. Chem. 1989, 54, 268−270.

• Hiiro, T., Morita, Y., Inoue, T., Kambe, N., Ogawa, A., Ryu, I., Sonoda, N. J. Am. Chem. Soc. 1990, 112, 455.

• Comasseto, J. V., Clososki, G. C., Cunha., Crabtree, R. H., Elsevier 2007, 9, 587-648.

• Dong, Z., Li, X., Liang, K., Mao, S., Huang, X., Yang, B., Xu,J., Liu, J., Luo, G., Shen, J. J. Org. Chem. 2007, 72, 606-609.

• Engman, L. J. Org. Chem. 1983, 48, 2920-2992.

• Al-Rubaie, A. Z., Al-Jadaan, S.A.N. Appl. Organomet. Chem. 1998, 12, 79-85.

• Khurana, J.M., Sharma, V., Chacko, S.A. Tetrahedron 2007, 63, 966-969.

Acknowledgement

• Dr. Jin Jin and Dr. Shaozhang Zang• Department of Chemistry• Western Illinois University• Family and Friends