David Tilly

Bimetallic combinations for dehalogenative metalation involving organic compounds.

Organic Compounds David Tilly,† Floris Chevallier,† Florence Mongin,*,† and Philippe C. Gros*,‡,§ †Equipe Chimie et Photonique Molećulaires, Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Universite ́ de Rennes 1, Bat̂iment 10A, Case 1003, Campus de Beaulieu, Avenue du Geńeŕal Leclerc, 35042 Rennes Ced́ex, France ‡HECRIN, Universite ́ de Lorraine, SRSMC UMR 7565, Boulevard des Aiguillettes, 54506 Vandoeuvre-les̀-Nancy, France HECRIN, CNRS, SRSMC UMR 7565, Boulevard des Aiguillettes, 54506 Vandoeuvre-les̀-Nancy, France

Cobalt mediated C–H bond functionalization: emerging tools for organic synthesis

This review provides a perspective on C–H bond functionalization mediated by cobalt complexes used in either stoichiometric or catalytic amounts, without the contribution of any other transition metal, for organic synthesis applications. The competitive cost, availability and lower toxicity of cobalt compared to precious transition metals constitute valuable advantages of the methods.

On the mechanism of the directed ortho and remote metalation reactions of N,N-dialkylbiphenyl 2-carboxamides.

A study concerning the mechanism of the LDA-mediated ortho and remote metalation of N,N-dialkyl-2-biphenyl carboxamides (e.g., 4a) is reported. On the basis of site-selective lithiation/electrophile quench experiments, including deuteration, the LDA metalation of 4 is proposed to involve initial amide-base complexation (CIPE) and equilibrium formation of 5, whose fast reaction with an in situ electrophile (TMSCl) to afford 6 prevents its equilibration with 7. In the absence of an electrophile, 5 undergoes equilibration via 4a with 7, whose fate is instantaneous cyclization to a stable tetrahedral carbinolamine oxide 8 which, only upon hydrolysis, affords fluorenone (3).

Computed CH Acidity of Biaryl Compounds and Their Deprotonative Metalation by Using a Mixed Lithium/Zinc‐TMP Base

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.

Combined directed ortho metalation—intramolecular Friedel–Crafts connections. Regiospecific route to 1-substituted fluoren-9-ones

Abstract ortho -Substituted-2-biphenyl carboxylic acids of the type 3a – j were prepared by the tandem metalation sequence from 2-biphenyl carboxylic acid 1 with sec -butyllithium in THF at −78°C followed by quenching with electrophiles. The carboxylic acids 3a – f were converted into 1-substituted fluorenones 4a – f upon treatment with methanesulfonic acid.