Tetrakis(dimethylamino)ethylene (TDAE)

Mark Redlich

In 2001, Professor William Dolbier, Jr., at the University of Florida reported¹ an approach to nucleophilic trifluoromethylation based on the generation of a trifluoromethyl anion using CF₃I in the presence of a powerful twoelectron reductant, tetrakis(dimethylamino)ethylene (TDAE) (Scheme 1).

Scheme 1

Over the ensuing years, Dolbier’s group has developed numerous reactions featuring this reagent system, including the trifluoromethylation of aldehydes and ketones,¹ cyclic sulfates,² disulfides and diselenides,³ and imines¹ (Scheme 2). In many cases, the TDAE/CF₃I method provided results that complement other nucleophilic trifluoromethylation reagents. Recently, Dolbier has expanded the use of his system to perfluoroalkylation,⁴ and was able to achieve similar results as with CF₃I; however, when the perfluorobutyl system was used, yields tended to decrease noticeably.

Scheme 2

TDAE has a reducing power comparable to zinc metal and as such has also been used as a reducing agent in organic synthesis. Recently, Vanelle and coworkers have exploited this reductive property to obtain epoxides from aldehydes and 2-(dibromomethyl)quinoxaline (Scheme 3),⁵ as well as α-chloroketones from aldehydes and 2-(trichloromethyl)-substituted azaheterocycles (Scheme 4).⁶ The Nishiyama group at Kansai University in Osaka has also used TDAE to obtain 1,2,3,4-tetrahydronaphthalenes from 1,2-bis(bromomethyl)arenes and olefins,⁷ and 1,4-diketones or diesters through reductive coupling of α-bromoketones or esters (Scheme 5).⁸

Scheme 3

Scheme 4

Scheme 5

Materials

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References

1. Aït-Mohand S, Takechi N, Médebielle M, Dolbier WR. 2001. Nucleophilic Trifluoromethylation Using Trifluoromethyl Iodide. A New and Simple Alternative for the Trifluoromethylation of Aldehydes and Ketones. Org. Lett.. 3(26):4271-4273. https://doi.org/10.1021/ol016933x

2. Takechi N, Ait-Mohand S, Medebielle M, Dolbier WR. 2002. Novel Nucleophilic Trifluoromethylation of Vicinal Diol Cyclic Sulfates. Org. Lett.. 4(26):4671-4672. https://doi.org/10.1021/ol0270374

3. Pooput C, Medebielle M, Dolbier WR. 2004. A New and Efficient Method for the Synthesis of Trifluoromethylthio- and Selenoethers. Org. Lett.. 6(2):301-303. https://doi.org/10.1021/ol036303q

4. Pooput C, Dolbier, WR, Médebielle M. 2006. Nucleophilic Perfluoroalkylation of Aldehydes, Ketones, Imines, Disulfides, and Diselenides. J. Org. Chem.. 71(9):3564-3568. https://doi.org/10.1021/jo060250j

5. Montana M, Terme T, Vanelle P. 2005. Original synthesis of oxiranes via TDAE methodology: reaction of 2,2-dibromomethylquinoxaline with aromatic aldehydes. Tetrahedron Letters. 46(48):8373-8376. https://doi.org/10.1016/j.tetlet.2005.09.152

6. Montana M, Terme T, Vanelle P. 2006. Original synthesis of ?-chloroketones in azaheterocyclic series using TDAE approach. Tetrahedron Letters. 47(37):6573-6576. https://doi.org/10.1016/j.tetlet.2006.07.030

7. Nishiyama Y, Kawabata H, Kobayashi A, Nishino T, Sonoda N. 2005. Reductive debromination of 1,2-bis(bromomethyl)arenes using tetrakis(dimethylamino)ethylene (TDAE). Tetrahedron Letters. 46(5):867-869. https://doi.org/10.1016/j.tetlet.2004.11.114

8. Nishiyama Y, Kobayashi A. 2006. Synthesis of 1,4-diketones: reaction of ?-bromo ketones with tetrakis(dimethylamino)ethylene (TDAE). Tetrahedron Letters. 47(31):5565-5567. https://doi.org/10.1016/j.tetlet.2006.05.141