Bromine-magnesium-exchange as a general tool for the preparation of polyfunctional aryl and heteroaryl magnesium-reagents

Abarbri, Mohamed; Dehmel, Florian; Knöchel, Paul

doi:10.1016/s0040-4039(99)01404-5

Cited by 137 publications

(53 citation statements)

References 19 publications

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“…This very general behavior leads to the high chemoselectivity of iodine or bromine-magnesium exchange reactions. 8,10,11 Chemoselective mono-Br/Mg-exchange has been observed in the case of dibromothiophenes (Scheme 3). [10][11][12] Thus, unsymmetrically substituted 2,3-dibromothiophenes such as 9 and 12 undergo highly chemo and regioselective Br/Mg-exchange at only 2-position to give 2-magnesiated thiophenes such as 10 and 13 leading to a variety of polyfunctional thiophenes such as 11 and 14 (Scheme 3).…”

Section: Five-membered Heterocyclesmentioning

confidence: 99%

“…8,10,11 Chemoselective mono-Br/Mg-exchange has been observed in the case of dibromothiophenes (Scheme 3). [10][11][12] Thus, unsymmetrically substituted 2,3-dibromothiophenes such as 9 and 12 undergo highly chemo and regioselective Br/Mg-exchange at only 2-position to give 2-magnesiated thiophenes such as 10 and 13 leading to a variety of polyfunctional thiophenes such as 11 and 14 (Scheme 3). 10,12 The presence of chelating groups in polyhalogenated heterocycles strongly influences the regioselectivity of the I/Mg-and Br/Mg-exchanges.…”

Section: Five-membered Heterocyclesmentioning

confidence: 99%

“…As expected, the second exchange is regioselective, leading after reaction with ethyl cyanoformate to the product 24 in 55% yield (Scheme 4). 10,11 The overall sequence shows the possibility of synthesizing polyfunctionalized imidazoles via regioselective Br/Mg-exchange reactions.…”

Section: Five-membered Heterocyclesmentioning

confidence: 99%

“…This very general behavior leads to the high chemoselectivity of iodine or bromine-magnesium exchange reactions. 8,10,11 …”

mentioning

confidence: 99%

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Preparation and Reactions of Heteroaryl Organomagnesium Compounds

Ila¹,

Baron²,

Wagner³

et al. 2005

Chemistry Letters

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The halogen/magnesium-exchange reaction has opened new perspectives in organic synthesis and has considerably extended the range of available functionalized aryl and heteroaryl magnesium compounds bearing functional groups such as ester, nitrile, iodide, imine, or even sensitive groups like nitro, hydroxy, and boronic esters. The present review summarizes the applications of these functionalized heteroaryl-and arylmagnesium compounds for the synthesis of a wide variety of regiospecifically functionalized five-and six-membered heterocycles. Ç 1. IntroductionThe selective functionalization of heteroaryl compounds is an important synthetic task. The resulting polyfunctional heteroaryl derivatives are often essential building blocks in the synthesis of natural products, 1 drugs, 2 new materials with defined properties, 3 or for the use in molecular recognition. 4 Although, directed metallation 5 or selective bromine/lithium-exchange 6 has provided a way to prepare a range of lithiated heterocycles, the high polarity of the carbon-lithium bond precludes the presence of sensitive functional groups such as ester and cyano groups in these lithium organometallics due to their too high reactivity. On the other hand, the more covalent character of the carbon-magnesium bond tolerates the presence of more functional groups. The synthesis of these polyfunctional Grignard reagents is, however, a problem, since the insertion of magnesium metal to aryl or heteroaryl halides bearing electron-withdrawing groups is inhibited by the presence of these functionalities. 7 Recently, we have shown that the halogen/magnesium-exchange reaction is a unique method for the preparation of a range of new functionalized aryl, alkenyl, and heteroaryl magnesium compounds, which has considerably extended the range of functionalized Grignard reagents available for synthetic purposes. These functionalized organomagnesium compounds have an excellent reactivity towards a wide range of electrophiles and they readily undergo transmetallation to provide a wide variety of organometallic reagents, particularly organocopper reagents which react especially well with soft electrophiles and display an excellent chemoselectivity. In the present review, we wish to report applications of this halogen/magnesium-exchange reactions for the preparation of a wide range of functionalized heteroaryl Grignard reagents and their reactions, which provide an entry to numerous polyfunctional five and six membered heterocyles. Ç 2. Synthesis of Functionalized Heterocycles Using Functionalized Heterocyclic Grignard ReagentsA variety of functionalized heterocyclic Grignard reagents can be prepared by using an I/Mg-or Br/Mg-exchange reaction.8 It was found earlier that aryl and heteroaryl iodides bearing electron-withdrawing groups undergo an I/Mg-exchange between À30 and À20C within a few hours, 8 and this exchange was applicable to a variety of heteroaryl iodides. The Br/Mgexchange 8 can also be applied to various heterocycles with electron-withdrawing groups. The elec...

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Section: Five-membered Heterocyclesmentioning

confidence: 99%

Section: Five-membered Heterocyclesmentioning

confidence: 99%

Section: Five-membered Heterocyclesmentioning

confidence: 99%

“…This very general behavior leads to the high chemoselectivity of iodine or bromine-magnesium exchange reactions. 8,10,11 …”

mentioning

confidence: 99%

See 2 more Smart Citations

Preparation and Reactions of Heteroaryl Organomagnesium Compounds

Ila¹,

Baron²,

Wagner³

et al. 2005

Chemistry Letters

Self Cite

View full text Add to dashboard Cite

show abstract

“…The addition of organometallic reagents to aldehydes has been one of the general methods for the synthesis of diarylmethanols. Of these reagents, organolithium and organomagnesium compounds are most frequently used for this purpose, but tolerate only a few electrophilic groups on themselves [4][5][6][7][8][9][10][11]. Examples of using other functionalized organometallic species [12][13][14][15][16][17][18][19] such as organocopper, organochromium, organotin, especially organozinc, have been described.…”

Section: Introductionmentioning

confidence: 99%