Computed CH acidity of biaryl compounds and their deprotonative metalation by using a mixed lithium/zinc-TMP base.

International audienceA no. of substituted biaryls, arylpyridines, arylpyrimidines and arylquinolines was prepd. by coupling reactions; deprotonation-iodination with a mixed lithium/zinc-TMP base gives the corresponding iodides. The obtained exptl. results on acidity are compared with calcd. values of Gibbs energies of deprotonation at different positions of the considered biaryl and arylheterocyclic systems. With the aim of synthesizing biaryl compds., several arom. iodides were prepd. by the deprotonative metalation of methoxybenzenes, 3-substituted naphthalenes, isoquinoline, and methoxypyridines by using a mixed lithium/zinc-TMP (TMP = 2,2,6,6-tetramethylpiperidino) base and subsequent iodolysis. The halides thus obtained, as well as com. compds., were cross-coupled under palladium catalysis (e.g., Suzuki coupling with 2,4-dimethoxy-5-pyrimidylboronic acid) to afford various representative biaryl compds. Deprotometalation of the latter compds. was performed by using the lithium/zinc-TMP base and evaluated by subsequent iodolysis. The outcome of these reactions has been discussed in light of the CH acidities of these substrates, as detd. in THF soln. by using the DFT B3LYP method. Except for in the presence of decidedly lower pKa values, the regioselectivities of the deprotometalation reactions tend to be governed by nearby coordinating atoms rather than by site acidities. In particular, azine and diazine nitrogen atoms have been shown to be efficient in inducing the reactions with the lithium/zinc-TMP base at adjacent sites (e.g., by using 1-(2-methoxyphenyl)isoquinoline, 4-(2,5-dimethoxyphenyl)-3-methoxypyridine, or 5-(2,5-dimethoxyphenyl)-2,4-dimethoxypyrimidine as the substrate), a behavior that has already been obsd. upon treatment with lithium amides under kinetic conditions. Finally, the iodinated biaryl derivs. were involved in palladium-catalyzed reactions. [on SciFinder(R)