Mitsunobu synthesis of symmetrical alkyl and polyfluoroalkyl secondary amines

Abstract

Trifluoromethanesulfonamides (triflamides) having the structure CF 3SO 2N[(CH 2) 3R] 2 (R = C n F 2 n + 1 or C n H 2 n + 1 , n = 4, 6, 8, 10) are obtained in high yields, when CF 3SO 2NH 2 is reacted with 3-perfluoroalkyl-1-propanols or the parent aliphatic alcohols in a Mitsunobu reaction (Ph 3P/[ i-PrO 2CN NCO 2- i-Pr]/ether). Products are isolated easily by fluorous extraction, fluorous solid–organic liquid filtration or n-heptane/CH 3OH extraction. Consecutive deprotection of triflamides with LiAlH 4 in boiling ether or dioxane solution affords the title amines in good overall yields. Fluorous partition coefficients of the F-tagged amides and amines are determined and qualitatively analyzed.