Exploring Structural Opportunities:The Regioflexible Substitution of 1,3-Difluorobenzene

摘要

To demonstrate the superiority of modern organometallic methods,the inexpensive starting material 1,3-difluorobenzene has been selectively converted into the three benzoic acids and all seven bromobenzoic acids containing he two fluorine atoms in homovicinal positions.The 2,6-difluorobenzoic acid (1)was prepared in a one-pot reaction consisting of direct metalaton and carboxylation.The key step on the route to the bromobenzoic acid 4 was a deprotonation-triggered brmine migration from the 2-to the 4-position.All other products were attained through (2,6-difluorophenyl)triethylsilane (11).Consecutive deprotonation of the sites adjacent to the fluorine atoms,followed by appropriate electrophilic substitution,provided not only the acid 7 but also the dibromo and iodobromo derivatives 13 and 23.These in turn gave the isomers 14 and 24 upon base-mediated migration of the heaviest halogen,which made the acids 8 and 10 directly accessible.The regiocontrolled monodebromination of intermediate 14 afforded (4-bromo-2,6-difluoro)triethylsilane (15),with opened the route to the acids 3 and 5 (by carboxylation and protodesilylation)and to acid 9 (by carboxylation and bromodesilylation).