François Trécourt

New Syntheses of Substituted Pyridines via Bromine–Magnesium Exchange

Abstract Bromine–magnesium exchange using i PrMgCl in THF at room temperature on 2-, 3- and 4-bromopyridines allowed the synthesis of various functionalized pyridines. The methodology was successfully used for the synthesis of 4-azaxanthone. Moreover, single exchange reactions observed on 2,6-, 3,5-, 2,3- and 2,5-dibromopyridines, with complete regioselectivity in the case of 2,3- and 2,5-dibromopyridines, afforded substituted bromopyridines, which were then involved in a second exchange step to provide difunctionalized pyridines.

Syntheses of substituted pyridines, quinolines and diazines via palladium-catalyzed cross-coupling of aryl Grignard reagents

Abstract The palladium-catalyzed cross-coupling reactions between arylmagnesium halides (phenylmagnesium chloride, mesitylmagnesium bromide, 4-(methoxycarbonyl)phenylmagnesium chloride and 4-cyanophenylmagnesium chloride) and halopyridines allowed the synthesis of substituted pyridines. Owing to the remarkably mild conditions used (often below 0°C), the reaction could be extended to the use of functionalized halopyridines, haloquinolines and halodiazines.

Pyridylmagnesium chlorides from bromo and dibromopyridines by brominemagnesium exchange: A convenient access to functionalized pyridines

Various bromopyridines were converted to the corresponding pyridylmagnesium chlorides at room temperature by treatment with iPrMgCl. The resulting Grignard reagents were quenched by various electrophiles to afford functionalized pyridines. The brominemagnesium exchange of some dibromopyridines was also studied.

Tributylmagnesium ate complex-mediated bromine–magnesium exchange of bromoquinolines: a convenient access to functionalized quinolines

2-, 3- and 4-bromoquinolines were converted to the corresponding lithium tri(quinolyl)magnesates at −10°C by treatment with Bu3MgLi in THF or toluene. The resulting organomagnesium derivatives were quenched by various electrophiles to afford functionalized quinolines.

Preparation of polyfunctional pyridines by a palladium(0)-catalyzed cross-coupling of functionalized aryl Grignard reagents

Abstract Difunctionalized pyridines can be prepared by a Pd(0)-catalyzed cross-coupling of functionalized arylmagnesium compounds with chloro- or bromopyridines at temperatures as low as −40°C. An addition–elimination mechanism involving a palladate intermediate is proposed.

Improved synthesis of 2,3-disubstituted pyridines by metallation of 2-chloropyridine: a convenient route to fused polyheterocycles

Chemoselective directed metallation of 2-chloropyridine allows the synthesis of 2-substituted 3-carbonylated pyridines, advantage being taken of the metallation ortho-directing effect of the halogen, as well as its reactivity towards nucleophiles. Thus (2-chloro-, 2-methoxy-, and 2-amino-3-pyridyl)-ethanones and -arylmethanones as well as carbaldehydes have been prepared. Some of these ortho-disubstituted intermediates have been readily cyclized to fused polyheterocycles such as naphthyridines and aza-analogues of coumarins, xanthones, and acridones.

New synthesis of Orelline by metalation of methoxypyridines

Abstract A new total synthesis in five steps of the alkaloid Orelline is reported. The methodology involves metalation of methoxypyridines to afford 2-halo-3,4-dimethoxypyridine on which an homocoupling reaction is performed to build the 2,2′-bipyridyl structure of the alkaloid.

First cross-coupling reactions of arylmagnesates: a convenient access to heteroarylquinolines

Abstract 2-, 3- and 4-Bromoquinolines were converted to the corresponding lithium tri(quinolyl)magnesates at −10°C on treatment with Bu3MgLi in THF. The resulting organomagnesium derivatives were involved in catalyzed cross-coupling reactions with heteroaryl bromides and chlorides to afford functionalized quinolines.

Synthesis and metallation of 2-(pyridyl)benzoic acids and ethyl 2-(pyridyl)benzoates: a new route to azafluorenones

The ring deprotonation of 2-(2- and 4-pyridyl)benzoic acids using lithium dialkylamides in THF at rt, and the in situ cyclization afforded 4- and 2-azafluorenones, respectively. 1-Azafluorenone was obtained from ethyl 2-(3-pyridyl)benzoate using a similar protocol.

Directed lithiation of unprotected pyridinecarboxylic acids

Abstract The lithium salts of 2-, 3- and 4-pyridinecarboxylic acids undergo deprotonation at the position adjacent to the carboxylate group when treated with LTMP in THF at 0 °C, −50 °C and −25 °C, respectively. The lithiation conditions could be extended to chloronicotinic acids, and even to an activated benzoic acid.