Categories: C-C Bond Formation > Heteroatom-containing Molecules > Trifluoromethylation
Synthesis of α-trifluoromethyl amines
TMSCF3 and tetrabutylammonium (triphenylsilyl) difluorosilicate (TBAT) were used for efficient nucleophilic trifluoromethylation of aromatic, aliphatic and α,β-unsaturated sulfonaldimines to yield the corresponding sulfonamide adducts in good to excellent yields.
G. K. S. Prakash, M. Mandal, G. A. Olah, Synlett, 2001, 77-78.
A nucleophilic trifluoromethylation reaction of carbonyl compounds with Ruppert’s reagent, Me3SiCF3, was efficiently promoted by a P(t-Bu)3-DMF system. Imines were also converted to the desired α-trifluoromethyl amines under similar reaction conditions.
S. Mizuta, N. Shibata, T. Sato, H. Fujimoto, S. Nakamura, T. Toru, Synlett, 2006, 267-270.>
Alkoxide-induced nucleophilic pentafluoroethylation and trifluoromethylation of aldehydes, ketones, and imines using pentafluoroethyl phenyl sulfone and trifluoromethyl phenyl sulfone, respectively, have been successfully achieved.
G. K. S. Prakash, Y. Wang, R. Mogi, J. Hu, T. Mathew, G. A. Olah, Org. Lett., 2010, 12, 2932-2935.
An iridium photocatalyst enables the addition of fluorinated groups to nitrones using ascorbic acid as a stoichiometric reducing agent. Partially fluorinated alkyl iodides can also be effectively used. The resulting hydroxylamines can be readily converted to valuable fluorinated amines by reduction with zinc.
V. I. Supranovich, V. V. Levin, M. I. Struchkova, A. D. Dilman, Org. Lett., 2018, 20, 840-843.
A BINOL-derived boro-phosphate catalyzes an enantioselective reduction of α-trifluoromethylated imines to provide chiral α-trifluoromethylated amines in high yields and with excellent enantioselectivities in the presence of catecholborane as hydride source under mild conditions.
H. He, X. Tang, Y. Cao, J. C. Antilla, J. Org. Chem., 2021, 86, 4336-4345.
The use of a commercially available Umemoto’s reagent enables a metal-free trifluoromethylation of nitroalkanes. This method provides quaternary α-(trifluoromethyl)nitroalkanes, that can be elaborated to various complex nitrogen-containing molecules, including α-(trifluoromethyl)amines.
A. S. Gietter-Burch, V. Devannah, D. A. Watson, Org. Lett., 2017, 19, 2957-2960.