Regioselective ring-opening of epoxides with ortho-lithioanisoles catalyzed by BF3·OEt2

It is presented that a number of o-2-hydroxyalkylanisoles could be efficiently synthesized through the regioselective ring-opening reaction of epoxides with o-lithioanisoles in the presence of BF3·OEt2 Lewis-acid catalyst. Sterically demanding o-lithioanisoles had to be generated by exploiting the combination of nBuLi and a catalytic amount of TMEDA (0.20 equiv) in Et2O as the lithiator whereas 'normal' anisole could be lithiated at ortho-position by treatment with nBuLi in THF as usual. Surprisingly, the availability of THF and a catalytic amount of TMEDA (0.20 equiv) in the reaction mixture was found to enhance the reaction yields dramatically. A complex aggregate formation by the co-operative ligation of THF and TMEDA to ortho-lithioanisole(s) was proposed to rationalize the high reactivity achieved in the ring-opening reaction of epoxides.