Guy Queguiner

Connection between metalation and cross-coupling strategies. A new convergent route to azacarbazoles

Abstract New convergent synthesis of azacarbazoles through metalation, cross-coupling reaction and intramolecular substitution via (2-aminobenzene)boronic acid and ortho-fluoroiodopyridines.

Directed Metalation of Pi-Deficient Azaaromatics: Strategies of Functionalization of Pyridines, Quinolines, and Diazines

Publisher Summary This chapter updates the directed ortho metalation (DoM) reaction of pyridines, quinolines, pyrimidines, pyrazines, and pyridazines. Various directed metalation group (DMGs) (halo, NHCOR and NHC02R, OR and OCONR2, 2-oxazolino, CONHR, CONR2, and masked RCHO and RCOR, SO2NR2) have been described, with major emphasis given to the metalation of halo pyridines, an area in which selectivity and mechanistic aspects have been extensively studied. Reactions of powerful alkyllithiums with halo pyridines, quinolines, and diazines may lead to nucleophilic substitution (by addition-elimination or hetaryne mechanisms), ring opening, halogen-scrambling, and coupling reactions that compete with the desired DoM process. Lithiation chemistry of bare pyridines and pyridine N-oxides is presented, followed by the use of the DoM strategy for the synthesis of natural products and biologically active molecules. The exploration of DoM chemistry in haloheteroaromatics is valuable for two reasons: (a) halo derivatives can be readily prepared from accessible amino, hydroxy, and, at times, unsubstituted systems, and (b) halogens can be subsequently induced to undergo a variety of funcionalizations via addition-elimination, metal-halogen exchange, and cross coupling reactions. Some of these transformations are more facile than in the aromatic series. Thus, DoM tactics may lead to diverse substituted heteroaromatics, which can be difficult to obtain by more classical means.

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.

New Polyfunctional Magnesium Reagents for Organic Synthesis

The iodine-magnesium exchange reaction allows the preparation of polyfunctional aryl, heteroaryl, or alkenyl magnesium reagents at low temperature. These reagents display the typical reactivity of Grignard compounds and undergo various copper-catalyzed reactions such as allylation or 1,4-addition. Using this halogen-metal exchange reaction, it was possible to generate polyfunctional magnesium reagents on the solid phase.

Selective alkylations of 1,4:3,6-dianhydro-d-glucitol (isosorbide)

Abstract Each of the two hydroxyl groups of isosorbide can be alkylated selectively, either by direct alkylation with benzyl chloride or allyl bromide according to the reaction conditions, or by a three-step procedure involving selective monoacetylation, alkylation with four different reagents, and finally deacetylation. Monobutyl and monomethyl derivatives from isosorbide are also described.

Metallation regioselective en serie pyridinique: Synthese originale d'amino-2 aroyl-3 pyridines

Abstract Lithium diisopropylamide reacts with 2-fluoropyridine at low temperature: regioselectivity is excellent and metallation occurs without side reactions such as nucleophilic attack. 2-Fluoro-3-lithiopyridine is formed and with aldehydes it gives the corresponding fluorinated alcohols which are then selectively oxidized. Halogen substitution using amines leads to various 3-oxoalkyl- or 3-aroyl-2-aminopyridines.

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

Summary Catalytic direct (hetero)arylation of (hetero)arenes is an attractive alternative to traditional Kumada, Stille, Negishi and Suzuki–Miyaura cross-coupling reactions, notably as it avoids the prior preparation and isolation of (hetero)arylmetals. Developments of this methodology in the oxazole series are reviewed in this article. Methodologies, selectivity, mechanism and future aspects are presented.

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.