Anne-Sophie Castanet

Mild and regioselective iodination of electron-rich aromatics with N-iodosuccinimide and catalytic trifluoroacetic acid

Abstract A variety of aromatics compounds substituted with methoxy or methyl groups were regioselectively iodinated with N -iodosuccinimide and catalytic trifluoroacetic acid with excellent yields under mild conditions and short reaction times.

Asymmetric Suzuki cross-coupling reaction: chirality reversal depending on the palladium–chiral phosphine ratio

Abstract Suzuki cross-coupling reaction with sterically hindered arylboronic acids is reported. Good yields are obtained by using DME and cesium fluoride in the presence of Pd(OAc)2 and triphenylphosphine. The catalytic asymmetric reaction between 2-methoxy-1-naphthylboronic acid and 1-iodo-2-methoxynaphthalene was studied in the presence of a palladium–chiral phosphine catalyst. When the reaction was carried out with Pd(OAc)2 and (R)-BINAP (versus (R)-TolBINAP), the enantioselection was dramatically influenced by the phosphine/palladium ratio.

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).

Biaryl synthesis via Suzuki coupling promoted by catalytic amounts of quaternary ammonium salts

Palladium-catalyzed Suzuki cross-coupling reaction (between phenylboronic acid and 4-bromobenzonitrile) in presence of catalytic quaternary ammonium salts is described. With Aliquat 336 (tricaprilylmethylammonium chloride), the rates of the reaction were increased in DME and toluene allowing to work with lower stirring and at lower temperatures in some cases.

ortho-Lithium/magnesium carboxylate-driven aromatic nucleophilic substitution reactions on unprotected naphthoic acids.

Substitution of an ortho-fluoro or methoxy group in 1- and 2-naphthoic acids furnishing substituted naphthoic acids occurs in good to excellent yields upon reaction with alkyl/vinyl/aryl organolithium and Grignard reagents, in the absence of a metal catalyst without the need to protect the carboxyl (CO(2)H) group. This novel nucleophilic aromatic substitution is presumed to proceed via a precoordination of the organometallic with the substrate, followed by an addition/elimination.

Synthesis of N-Aryl and N-Alkyl Anthranilic Acids via SNAr Reaction of Unprotected 2-Fluoro- and 2-Methoxybenzoic Acids by Lithioamides

Substitution of the fluoro or methoxy group in unprotected 2-fluoro- and 2-methoxybenzoic acids to afford N-aryl and N-alkyl anthranilic acids occurs upon reaction with lithioamides under mild conditions in the absence of a metal catalyst.

Chemoselective deprotonative lithiation of azobenzenes: reactions and mechanisms.

Whereas standard strong bases (n-BuLi, s-BuLi/TMEDA, n-BuLi/t-BuOK, TMPMgCl·LiCl, and LDA) reduce the N═N bond of the parent azobenzene (Y = H), aromatic H→Li permutation occurs with LTMP when a suitable director of lithiation (Y = OMe, CONEt2, F) is present in the benzene residue of the azo compound. The method allows direct access to new substituted azobenzenes.

Selectivity in C-alkylation of dianions of protected 6-methyluridine

Summary A regioselective synthesis of 6-ω-alkenyluridines 3, precursors of potent antiviral and antitumor cyclonucleosides 5, is described. While ω-alkenyl halides do not alkylate 6-lithiouridine, compounds 3 were prepared in a regioselective manner by sequential treatment of 6-methyluridine 2 with LTMP or LDA (4 equiv) in THF at −30 °C followed by alkylation with ω-alkenyl bromides.

Highly Efficient Heterobimetallic Iron‐Magnesium‐HMPA–Catalyzed Michael‐type Friedel–Crafts Reactions of Indoles and Chalcones

Abstract A simple and novel bimetallic catalyst, an iron and magnesium complex (Fe‐Mg‐hexamethylphosphoramide (HMPA)), with dual activation was found to be an effective and promising catalyst for the Michael‐type Friedel–Crafts reactions of indoles with chalcones. This novel catalytic system has the advantages of highly efficient, mild reaction conditions and exhibits high reactivity and selectivity, which make it a useful and attractive process for the synthesis of indole derivatives.

Ortholithiation of Unprotected Benzoic Acids: Application for Novel 2‐Chloro‐6‐Substituted Benzoic Acid Syntheses

Abstract 2‐Chloro‐6‐substituted benzoic acids of the type 2a–h were prepared by the tandem metallation sequence from 2‐chlorobenzoic acid 1 with the 1:1 complex sec‐butyllithium/TMEDA in THF at −78°C followed by quenching with electrophiles.