title: Computed CH acidity of biaryl compounds and their deprotonative metalation by using a mixed lithium/zinc-TMP base.
abstract: With the aim of synthesizing biaryl compounds, several aromatic iodides were prepared 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 commercial compounds, were cross-coupled under palladium catalysis (e.g., Suzuki coupling with 2,4-dimethoxy-5-pyrimidylboronic acid) to afford various representative biaryl compounds. Deprotometalation of the latter compounds 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 determined in THF solution 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 observed upon treatment with lithium amides under kinetic conditions. Finally, the iodinated biaryl derivatives were involved in palladium-catalyzed reactions.
authors.affiliation: Equipe Chimie et Photonique Moléculaires, Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1, Bâtiment 10A, Case 1003, Campus Scientifique de Beaulieu, 35042 Rennes, France.
authors.forename: Raghu Ram
authors.initials: RR
authors.lastname: Kadiyala
authors.forename: David
authors.initials: D
authors.lastname: Tilly
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Nagaradja
authors.forename: Thierry
authors.initials: T
authors.lastname: Roisnel
authors.forename: Vadim E
authors.initials: VE
authors.lastname: Matulis
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Ivashkevich
authors.forename: Yury S
authors.initials: YS
authors.lastname: Halauko
authors.forename: Floris
authors.initials: F
authors.lastname: Chevallier
authors.forename: Philippe C
authors.initials: PC
authors.lastname: Gros
authors.forename: Florence
authors.initials: F
authors.lastname: Mongin
mesh_terms: D000577:Amides / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006847:Hydrocarbons, Iodinated / Q000737:chemistry*; D007700:Kinetics; D008094:Lithium / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
chemical_list: D000577:Amides; D006571:Heterocyclic Compounds; D006847:Hydrocarbons, Iodinated; D010880:Piperidines; C551336:2,2,6,6-tetramethylpiperidide; D010165:Palladium; D008094:Lithium; D015032:Zinc