Novel generation ponytails in fluorous chemistry: Syntheses of primary, secondary, and tertiary (nonafluoro-tert-butyloxy)ethyl amines

(Nonafluoro-tert-butyloxy)ethyl tosylate 4 was prepared in 65% yield from nonafluoro-tert-butanol 1 using commercially available reagents. Further reaction of 4 with HNR1R2 (R1 = R2 = H, CH3; R1 = H, R2 = CH3, (CH2)3C8F17, CH2CH2OC(CF3)3) affords the appropriate (CF3)3COCH2CH2NR1R2 amines in 20–69% yields. Improved overall yields of [(CF3)3COCH2CH2]3−nNRn to 1 were obtained by the reaction of (CF3)3CONa 2 and (XCH2CH2)3−nNRn (X = Cl, n = 0, 1, 2, R = CH3; X = CH3SO2O, n = 1, R = CH3SO2) nitrogen mustards and a similar reactive β-substituted ethyl amine. The title amines are mobile colorless liquids and volatile with steam. The bulky fluorous ponytail (CF3)3CO(CH2)2 displays high acidic stability and increases fluorous character almost as much as the classical straight-chain C8F17(CH2)3 ponytail.

Graphical abstract(Perfluoro-tert-butoxy)ethyl tosylate was easily made in three steps from commercially available nonafluoro-tert-butanol. The alkylation of selected amines with this fluorous tagging reagent afforded the appropriate primary, secondary and tertiary amines in acceptable yields. Amines with two or three (perfluoro-tert-butoxy)ethyl groups can also be made by the O-alkylation of sodium nonafluoro-tert-butoxide using nitrogen mustards or related reagents. Figure optionsDownload full-size imageDownload as PowerPoint slide