Practice of fluorous biphase chemistry: convenient synthesis of novel fluorophilic ethers via a Mitsunobu reaction

Abstract

The evolution of the term fluorous is addressed first, then a concise terminology is proposed, including fluorous partition coefficient, specific fluorophilicity and fluorousness. Some examples are shown for the design of higher generation fluorophilic molecules, involving Class I to Class III ponytails. Fluorophilic ethers of the structure of ArC(CF 3) 2O(CH 2) m (CF 2) n F ( m=1, n=1, 7; m=3, n=8) are obtained in high yields, when 2-aryl-1,1,1,3,3,3-hexafluoro-propanols are reacted either with trifluoroethyl- and 1 H,1 H-perfluorooctyl triflates (NaH/DMF, Williamson ether synthesis) or with 3-perfluorooctyl-propanol (Ph 3P/EtO 2CNNCO 2Et/PhCF 3, Mitsunobu reaction), respectively. Fluorophilic phenol- and perfluoro- tert-butyl ethers can also be prepared effectively by the latter method. In case of higher homologues ( n=7, 8) product isolation can be facilitated using fluorous extraction (C 6F 14/CH 3OH). Specific fluorophilicity values of target molecules are estimated using a 2D method and compared with experimentally determined ones.