Tributylmagnesium ate complex-mediated novel bromine–magnesium exchange reaction for selective monosubstitution of dibromoarenes

Iida, Takehiko; Wada, Toshihiro; Tomimoto, Koji; Mase, Toshiaki

doi:10.1016/s0040-4039(01)00861-9

Cited by 112 publications

(55 citation statements)

References 18 publications

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“…Deprotection to 3,5-dichloro-2-(trifluoromethyl)benzoic acid (9; 84 %) was accomplished in three steps. First, bromine was replaced by magnesium using lithium tributylmagnesate, [19,20] and the resulting compound was neutralized with dilute acid before the trimethylsilyl group was removed with TBAF hydrate.…”

Section: Resultsmentioning

confidence: 99%

Metalation and Derivatization of All Six Dichlorobenzotrifluorides:Site Selectivities

et al. 2005

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The metalation of 2,3-, 2,6-, 2,4-and 3,5-dichlorobenzotrifluorides can be readily effected with standard reagents such as lithium diisopropylamide, lithium 2,2,6,6-tetramethylpiperidide, and butyllithium at the chlorine-adjacent 4-and 3-positions and the chlorine-flanked 3-and 4-positions, respectively. However, regioselectivity was secured with 2,6-dichlorobenzotrifluoride only under equilibrating conditions as the initial deprotonation occurs simultaneously at the 3-and 4-positions. 3,4-Dichlorobenzotrifluoride requires methyllith-

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Section: Resultsmentioning

confidence: 99%

Metalation and Derivatization of All Six Dichlorobenzotrifluorides:Site Selectivities

et al. 2005

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“…"Metal tuning" should offer a valid solution. If lithiated species prove to be too reactive, one may try magnesium or zinc derivatives (set free from bromo-or iodopyrimidines by treatment with lithium tributylmagnesate [31,32] or diethylzinc, respectively). The heavy halogen-bearing precursor should be readily accessible by bromodesilylation [33][34][35][36] or iododesilylation [33][34][35] of silanes prepared by in situ trapping of lithiated pyrimidines with chlorotrimethylsilane or chlorotriethylsilane.…”

Section: Discussionmentioning

confidence: 99%

Metal‐Bearing and Trifluoromethyl‐Substituted Pyrimidines: Generation and Functionalization

2006

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Keywords: Functionalization / Halogen/metal permutation / Metalation / Nucleophilic addition / Pyrimidines / Single electron transfer / Trifluoromethyl groups 5-Pyrimidyllithium species are fairly stable when the metal is flanked by two electron-withdrawing substituents such as trifluoromethyl and chlorine or bromine. Thus, the corresponding 5-carboxylic acids are produced in high yields from 4,5-dibromo-6-(trifluoromethyl)pyrimidine and 5-bromo-4-chloro-6-(trifluoromethyl)pyrimidine upon halogen/metal permutation accomplished with isopropylmagnesium chloride or butyllithium followed by carboxylation. Satisfactory or excellent yields of 5-carboxylic acids are equally obtained when 4-chloro-, 2,4-dichloro-and 2,4-dibromo-6-(trifluoromethyl)pyrimidine are deprotonated with lithium diisopro-

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“…[56] Exactly the same methods were used to convert the isologous 2-chloro-6-(trifluoromethyl)pyridine into 2-chloro-6-(trifluoromethyl)pyridine-3-carboxylic acid (39; 60 % overall yield), 6-chloro-2-(trifluoromethyl)pyridine-3-carboxylic acid (40; 79 %), and 2-chloro-6-(trifluoromethyl)pyridine-4-carboxylic acid (41; 51 % overall yield; Scheme 14). [57] The only difference was that the iodine/lithium permutation was performed with lithium tributylmagnesate [60,61] rather than with the less reactive isopropylmagnesium chloride. The single halogen atom at the 2-or 6-position of the acids 37-41 is of course prone to replacement by any standard nucleophile.…”

Section: Cf 3 -Bearing Building Blocksmentioning

confidence: 99%

CF₃‐Bearing Aromatic and Heterocyclic Building Blocks

2006

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Fluorine remains an insiders' tip in the life sciences as it enables the fine-tuning of biological properties. However, the synthesis of fluorine-substituted target compounds is not always trivial. Virtually any fluorine atom attached to an organic backbone has ultimately to be imported from inorganic sources. Crucial for the entire synthetic planning in medicinal and agricultural research is the decision on at what stage and how the halogen will be introduced. Standard technical processes, in particular the displacement of chlorine using anhydrous hydrogen fluoride or potassium fluoride, can hardly be implemented rationally on the laboratory scale. Universal methods that are applicable by both industrial and academic researchers thus have great appeal. If a trifluoromethyl-substituted arene or heterocycle is the target compound, two splendid options exist. The CF(3) group can be delivered packagewise by coupling an appropriate substrate with in situ generated (trifluoromethyl)copper. Alternatively, one may start from a CF(3)-substituted arene or heterocycle as a core and complete it with the missing parts of the ultimate structure.

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Tributylmagnesium ate complex-mediated novel bromine–magnesium exchange reaction for selective monosubstitution of dibromoarenes

Cited by 112 publications

References 18 publications

Metalation and Derivatization of All Six Dichlorobenzotrifluorides:Site Selectivities

Metalation and Derivatization of All Six Dichlorobenzotrifluorides:Site Selectivities

Metal‐Bearing and Trifluoromethyl‐Substituted Pyrimidines: Generation and Functionalization

CF₃‐Bearing Aromatic and Heterocyclic Building Blocks

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Tributylmagnesium ate complex-mediated novel bromine–magnesium exchange reaction for selective monosubstitution of dibromoarenes

Cited by 112 publications

References 18 publications

Metalation and Derivatization of All Six Dichlorobenzotrifluorides:Site Selectivities

Metalation and Derivatization of All Six Dichlorobenzotrifluorides:Site Selectivities

Metal‐Bearing and Trifluoromethyl‐Substituted Pyrimidines: Generation and Functionalization

CF3‐Bearing Aromatic and Heterocyclic Building Blocks

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CF₃‐Bearing Aromatic and Heterocyclic Building Blocks