SELECTIVITIES IN REACTIONS OF ORGANOLITHIUM REAGENTS WITH ARYL BROMIDES WHICH BEAR PROTON-DONATING GROUPS

Studies of substrates which offer an acidic hydrogen and an aryl bromi de for reaction with an organolithium reagent have been carried out wi th a series of benzene bromo amides and bromo anilides as well as sele cted benzene bromo carboxylic acids, bromoanilines, and bromobenzylami nes. A representative example is the reaction of N-ethyl-N-deutero-o-b romobenzamide (6-d) with 1-lithio-3-phenylpropane to give N-ethyl-o-de uterobenzamide (46%, 94%-d) (7-d), N-ethyl-o-bromobenzamide (6)(49%), 3-deutero-1-phenylpropane(51%, 92%-d), and 1-bromo-3-phenylpropane (48 %). Product formation in this and related cases is explained by the op eration of a two step sequence in which an initial deprotonation is fo llowed by a bromine-lithium exchange which is accelerated with respect to mixing. Such a sequence is consistent with the results of deuteriu m labeling and with changes in product ratios on different mixing and with differently aggregated organolithium reagents. Support is provide d for the operation of two pathways for the expedited bromine-lithium exchange reactions. In one pathway a high local concentration of the o rganolithium reagent promotes rapid reaction and in the second the exc hange reaction occurs within an initially formed complex. The selectiv ity for removal of a bromine ortho to a lithiated carboxamide is found to be 5-8 with n-butyllithium, and satisfactory synthetic ortho selec tivity is obtained for N-ethyl-2,5-dibromobenzamide with phenyllithium .