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

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))(2)O(CH(2))(m)(CF(2))(n)F (m = 1. n = 1. 7 m = 3, it = 8) are obtained in high yields, when 2-aryl- 1, 1, 1,3,3,3-hexafluoro-propanols are reacted either with trifluoroethyl- and 1H. 1H-perfluorooetyl triflates (NaH/ DMF, Williamson ether synthesis) or with 3-perfluorooctyl-propanol (Ph(3)P/EtO(2)CN=NCO(2)Et/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(6)F(14)/CH(3)OH). Specific fluorophilicity values of target molecules are estimated using a 2D method and compared with experimentally determined ones. (C) 2002 Elsevier Science B.V. All rights reserved.