Synthesis of functionalized nitroarylmagnesium halides via an iodine-magnesium exchange

[reaction: see text] Various nitro-substituted aryl and heteroaryl iodides undergo an iodine-magnesium exchange reaction when treated with PhMgCl leading to nitro-containing magnesium organometallics. These Grignard reagents display an excellent stability at temperatures below -40 degrees C and do not undergo electron-transfer reactions. They react as expected with various electrophiles.     

Preparation of 2-magnesiated 1,3,5-triazines via an iodine-magnesium exchange

Functionalized iodo- and diiodo-1,3,5-triazine derivatives readily undergo an I/Mg exchange with BuMgCl, sBuMgCl, or OctMgBr at low temperatures furnishing 2-magnesiated and 2-zincated 1,3,5-triazines (after transmetalation with ZnCl(2)). This method also offers a convenient access to dimagnesiated triazines. Furthermore, it allows the preparation of functionalized 1,3,5-triazinyl dimers and trimers, interesting for their opto-electronic properties.     

Synthesis of cyclopropanes via iodine-magnesium exchange between 3-iodomethyl-1-oxacyclopentanes and organomagnesium reagents

Iodine-magnesium exchange occurs upon treatment of 3-iodomethyl-1-oxacyclopentanes with alkyl Grignard reagents or trialkylmagnesate. The resulting organomagnesium compounds undergo intramolecular nucleophilic substitution in ether to afford cyclopropane skeletons in a stereoselective manner.     

Preparation of polyfunctional heterocycles using highly functionalized aminated arylmagnesium reagents as versatile scaffolds

[reaction: see text] Functionalized Grignard reagents, derived from readily available o-iodoaniline derivatives and obtained via a straightforward iodine-magnesium exchange, can be used to prepare a wide range of polyfunctional indoles, quinolines, and quinazolinones.     

Stereoselective preparation of highly functionalized (Z)-3-magnesiated enoates by an iodine-magnesium exchange reaction

3-Iodoenoates are converted into the corresponding alkenylmagnesium species with complete retention of configuration of the double bond; both direct reaction and copper(I)-mediated reactions with various electrophiles provide polyfunctional enoates.     

Preparation of polyfunctional arylmagnesium reagents bearing a triazene moiety. A new carbazole synthesis

[reaction: see text] The reaction of iodo- or bromo-substituted aryltriazenes with i-PrMgCl.LiCl generates the corresponding magnesiated derivatives which react with various electrophiles (acid chlorides, 3-iodoenones, allylic halides, aldehydes) affording polyfunctional triazenes. They can be readily converted to the corresponding polyfunctional aryl iodides. This new synthetic strategy was applied to prepare functionalized carbazoles.     

Grignard reagents: alkoxide-directed iodine-magnesium exchange at sp3 centers

Sequential addition of i-PrMgCl and BuLi to sp3 hybridized iodoalcohols triggers a facile iodine-metal exchange. Intercepting the resulting cyclic Grignard reagents with a slight excess of an electrophile leads to a diverse range of substituted alcohols. The iodine-magnesium exchange strategy is effective with 3-carbon iodoalcohols bearing alkyl substitutents on the carbinol or adjacent carbons and with the chain-extended homolog 4-iodobutan-1-ol.     

New stereoselective preparation of (Z)-3-perfluoroalkyl-3-magnesiated enoates by an iodine-magnesium exchange reaction

(Z)-Ethyl-3-perfluoroalkyl-3-magnesiated crotonates were prepared from (Z)-ethyl-3-perfluoroalkyl-3-iodo enoates by iodine-magnesium exchange reaction with isopropylmagnesium bromide in THF at -78 degrees C. These new reagents reacted with a range of electrophiles, leading to polyfunctional products bearing a perfluoroalkyl group.     

Direct preparation of copper organometallics bearing an aldehyde function via an iodine-copper exchange

The iodine-copper exchange reaction allows the direct preparation of various aryl, heteroaryl and alkenyl cuprates bearing a formyl group, thus allowing a direct synthesis of polyfunctional aldehydes without the need of protecting groups or an additional oxidation step.     

Preparation of new polyfunctional magnesiated heterocycles using a chlorine-, bromine-, or iodine-magnesium exchange

The reaction of heteroaryl iodides with i-PrMgBr (ca. 1.0 equiv) in THF provides the corresponding magnesiated heterocycles. Functional groups such as an ester, cyano, or chloride functions are tolerated in these new Grignard reagents if the exchange can be performed below -20 degrees C. This is the case for all heterocycles bearing electron-withdrawing groups or chelating functions facilitating the iodine-magnesium exchange. In many cases, the exchange can be extended to heteroaryl bromides, and a case of a chlorine-magnesium exchange is described with tetrachlorothiophene. This new preparation of functionalized heteroarylmagnesium compounds provides after reaction with various electrophiles a new entry to a broad range of polyfunctional pyridines, imidazoles, furanes, thiophenes, pyrroles, antipyrines, and uracil derivatives. The application of the halogen-magnesium exchange in the solid phase allows the performance of solid-phase synthesis, with potential applications for combinatorial chemistry.     

A new general preparation of polyfunctional diarylamines by the addition of functionalized arylmagnesium compounds to nitroarenes

The addition of functionalized arylmagnesium halides to nitroarenes in THF (-20 degrees C, 2 h) provides, after reductive workup (FeCl(2), NaBH(4)), various polyfunctional diarylamines in 63-86% yield. Heterocyclic arylated amines can be prepared by this one-pot procedure. A mechanistic rationale of this reaction is given.     

Synthesis of functionalized diarylmethanes via a copper-catalyzed cross-coupling of arylmagnesium reagents with benzylic phosphates

A combination of copper chloride, triethyl phosphite, and tetrabutylammonium iodide is a very efficient catalytic system for the synthesis of polyfunctionalized diarylmethanes, using the cross-coupling reaction of arylmagnesium halides with benzylic phosphates. The antibiotic Trimethoprim has been prepared using this Cu(I)-catalyzed cross-coupling in 52% overall yield (four steps).     

Iron-catalyzed homo-coupling of simple and functionalized arylmagnesium reagents

Iron-catalyzed homo-coupling of simple and functionalized arylmagnesium reagents is described. The reaction is highly chemoselective (CN, COOEt and NO(2) groups are tolerated). The procedure was used to perform intramolecular couplings. This cyclization reaction is the key step of the total synthesis of the N-methylcrinasiadine.     

Preparation of cyclic alkenylmagnesium reagents via an iodine/magnesium exchange

The reaction of various cyclic alkenyl iodides with i-PrMgCl.LiCl produces the corresponding alkenylmagnesium reagents under mild conditions. After reaction with various electrophiles, like allylic halides, disulfides, aldehydes and acid chlorides, the expected products are obtained in 53-91% yield. Remarkably, the mild conditions of the I/Mg-exchange tolerate the presence of sensitive diene functionalities.     

Synthesis of arylboronic acids via the reaction of borane with arylmagnesium halides

The reaction of borane complexes with arylmagnesium halides produces the corresponding arylborohydrides in high yield. The arylborohydrides are readily hydrolyzed to the arylboronic acids. The syntheses are conveniently carried out in one pot. The reaction mechanism was clarified via a boron-11 NMR study.     

Microwave-promoted synthesis of amino-substituted 2-pyridone derivatives via palladium-catalyzed amination reaction

A rapid and efficient synthesis of amino-substituted 2-pyridones was demonstrated by palladium-catalyzed amination reaction under microwave irradiation. This high-speed synthesis provided a number of amino-substituted 2-pyridones from the corresponding bromo-2-benzyloxypyridines via palladium-catalyzed amination followed by hydrogenolysis of benzyl ether.     

Selective functionalization of imidazoles via an iodine-copper exchange reaction

The reaction of protected 4,5-diiodoimidazoles with (PhMe2CCH2)2CuLi regioselectively provides 5-cuprated imidazoles, which readily react with various electrophiles furnishing functionalized imidazoles in good yields; remarkably, these resulting mono-iodoimidazoles undergo again an iodine-copper exchange reaction in the presence of sensitive functional groups, like an aldehyde or a ketone.     

Novel ferrocene-containing helical triangular macrocycle achieved via an exchange reaction

A novel ferrocene-containing helical triangular macrocyclic compound has been constructed through an exchange reaction of hydrazone groups which templated and catalyzed by Co(II) ions.