Tetrakis(dimethylamino)ethylene (TDAE)

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).

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.

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