Giese Radical Addition

17 November, 2015 / by SK / in Reactions

12197

Overall Score4

Generality
Reagent Availability
Experimental User Friendliness

General Characteristics

Carbon free-radicals (generated from organic halides, the Barton esters, etc.) are nucleophilic and can be trapped with various electrophiles.

In particular, trapping of free-radicals with electron-deficient alkenes to form carbon-carbon bonds is called the Giese reaction. The newly formed α-carbon radicals can be reacted further with the second electrophiles in tandem fashion.

The application of this reaction in intramolecular cyclization is common in natural product synthesis.

General References

Giese, B.; Gonzalez-Gomez, J. A.; Witzel, T. Angew. Chem. Int. Ed. Engl. 1984, 23, 69. DOI: 10.1002/anie.198400691

Girse, B. Angew. Chem. Int. Ed. Engl. 1983, 22, 753. DOI: 10.1002/anie.198307531
Zhang, W. Tetrahedron 2001, 57, 7237. DOI: 10.1016/S0040-4020(01)00634-2
Srikanth, G. S. C.; Castle, S. L. Tetrahedron 2005, 61, 10377. doi:10.1016/j.tet.2005.07.077

Jasperese, C. PO.; Curran, D. P.; Fevig, T. L. Chem. Rev. 1991, 91, 1237. doi:10.1021/cr00006a006
Salom-Roig, X. J.; Denes, F.; Renaud, P. Synthesis 2004, 1903. DOI: 10.1055/s-2004-831161
Rowland, G. J. Tetrahedron 2009, 65, 8603. doi:10.1016/j.tet.2009.07.001
Rowland, G. J. Tetrahedron 2010, 66, 1593. doi:10.1016/j.tet.2009.12.023

Reaction Mechanism

Examples

The tandem Giese reaction using organic tellurium reagent.^[1]

The synthesis of sterically congested carbon-carbon bonds by visible-light redox catalysis (the Okada-Overman conditions).^[2]

The Giese radical reaction can involve carbonyl insertion under CO atmosphere.^[3,4]

Experimental Procedure
Experimental Tips
References

[1] Kamimura, D.; Urabe, D.; Nagatomo, M.; Inoue, M. Org. Lett. 2013, 15, 5122. DOI: 10.1021/ol402563v
[2] (a) Okada, K.; Okamoto, K.; Morita, N.; Okubo, K.; Oda, M. J. Am. Chem. Soc. 1991, 113, 9401. DOI: 10.1021/ja00024a074 (b) Schnermann, M. J.; Overman, L. E. Angew. Chem. Int. Ed. 2012, 51, 9576. DOI: 10.1002/anie.201204977 (c) Lackner, G. L.; Quasdorf, K. W.; Overman, L. E. J. Am. Chem. Soc. 2013, 135, 15342. DOI: 10.1021/ja408971t
[3] Miura, K.; Tojino, M.; Fujisawa, N.; Hosomi, A.; Ryu, I. Angew. Chem. Int. Ed. 2004, 43, 2423. DOI:10.1002/anie.200453702
[4] Review: (a) Ryu, I.; Sonoda, N. Angew. Chem. Int. Ed. 1996, 35, 1050. DOI: 10.1002/anie.199610501 (b) Ryu, I.; Sonoda, B.; Curran, D. P. Chem. Rev. 1996, 96, 177. DOI: 10.1021/cr9400626 (c) Ryu, I. Chem. Soc. Rev. 2001, 30, 16. DOI: 10.1039/A904591K