3,4,5-Trimethoxyphenyllithium

The 3,4,5-trimethoxypIieiiyl substituent is a frequently encountered substructure in a variety o f natural products. Therefore, it would be useful if this group could be introduced via a carbon-carbon bond forming reaction of the 3,4,5-trimethoxyphenyl carbanion and an appropriate carbon electro-phile. We recently encountered a need to effect such a transformation and were surprised to learn of only a single report' regarding the preparation and use of thls anion. 3,4,5-Trimetlioxyphenyl bromide (1) was lithiated with E-butyllithium and carboxylated to generate 3,4,5-trimethoxybenzoic acid in 15% yield. In contrast 2,3,4-trimethoxyphenyl bromide has been lithiated and then methylated quite effiiently. We report here that the generation of 3,4,5-trimethoxyphenyllithium (2) from the bromide or iodide and Its subsequent addition to a variety of electrophiles is a straightforward and effective method for incorporation of this unit via C-C bond formation.