Multiple Regioselective Functionalizations of Quinolines via Magnesiations

Boudet, Nadège; Lachs, Jennifer R.; Knöchel, Paul

doi:10.1021/ol702494k

Cited by 90 publications

(52 citation statements)

References 26 publications

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“…These exchange reactions can also be extended to quinolines and allow their multiple regioselective functionalization including a total synthesis of the biologically active molecule talnetant in less than six steps starting with a commercially available quinoline derivative [65]. Also, the regioselective I/Mg-exchange of diiodopyridines such as 84 can be realized under mild conditions.…”

Section: Regioselective Functionalization Of Pyridines Via a Halogen/mentioning

confidence: 99%

Review. Regioselective Functionalization of Pyridines using a Directed Metalation or a Halogen/Metal Exchange

Manolikakes

Barl

Sämann

et al. 2013

Zeitschrift Für Naturforschung B

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This review describes the various ways of functionalizing the pyridine scaffold using either directed metalation or halogen/metal exchange. Deprotonation can be accomplished with different lithium amides or alkyllithium reagents at low temperature. Milder conditions and higher functional group tolerance can be achieved by using ate-bases with different metals (Cd, Mg, Zn) or TMP (2,2,6,6-tetramethylpiperidyl) metal reagents (metal = Mg, Zn, Zr). With alkyllithium reagents it is also possible, by carefully adjusting the reaction conditions, to perform bromine/lithium exchange reactions. Organomagnesium reagents, like iPrMgX (X = Br, Cl·LiCl), may be used for exchanging more sensitive iodinated or brominated pyridines.

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Section: Regioselective Functionalization Of Pyridines Via a Halogen/mentioning

confidence: 99%

Review. Regioselective Functionalization of Pyridines using a Directed Metalation or a Halogen/Metal Exchange

Manolikakes

Barl

Sämann

et al. 2013

Zeitschrift Für Naturforschung B

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“…Less reactive reagents, such as MesMgCl·LiCl or Mes 2 Mg·2LiBr.TMEDA (TMEDA, N,N,N',N'-tetramethylethylenediamine), enable selective exchanges on polybrominated compounds as illustrated with the formation of the Grignard reagent 15 (Scheme 5.2) [23]. The preparation of oligofunctional alkylmagnesium compounds by halogen/Mg exchange is much more challenging, as the higher reactivity of the alkyl-magnesium bond limits its functional group tolerance.…”

Section: Halogen-magnesium Exchange Reactionsmentioning

confidence: 99%

Carbon–Carbon‐Bond‐Forming Reactions Mediated by Organomagnesium Reagents

Chemla

Ferreira

Pérez‐Luna

et al. 2013

Metal‐Catalyzed Cross‐Coupling Reactions and More

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IntroductionFirst reported at the beginning of the twentieth century [1], organomagnesiums are very important synthetic tools. In the field of coupling reactions, first examples of transition-metal-mediated reactions have been reported by Gilman and Lichtenwalter [2] with the oxidative homo-coupling of aryl Grignard reagents in the presence of transition metal halides as both catalyst precursors and oxidants. This reaction was later greatly improved by Kharasch [3], who showed that an efficient homo-coupling reaction could be observed with a small amount of CoCl 2 (3 mol%) and an organic halide as a stoichiometric oxidant. This breakthrough was then followed by the report in 1941 on cross-coupling reactions of arylmagnesium bromides with vinylic halides in the presence of various transition metal salts by the same group [4]. Surprisingly, this seminal work remained mainly unexploited, until this reaction was reinvestigated by several groups in the beginning of the 1970s [5]. Thus, Kochi and Tamura [6, 7] described in 1971 the use of Fe(III) salts as catalyst precursors for cross-coupling reactions, while Kumada [8] and Corriu [9] reported the use of nickel for similar transformations [10,11]. At the same time, the group of Normant [12] described the Cu-catalyzed reaction of the Grignard reagents with organic halides, followed by the report of Murahashi [13] on the use of palladium as a catalyst in similar cross-couplings. Most cross-coupling reactions have been performed with unfunctionalized Grignard reagents because no general method for preparing oligofunctional organomagnesium reagents was available. However, the situation is rapidly evolving, thanks to the groundbreaking work of Knochel and coworkers [14] on the preparation of highly functionalized Grignard reagents. In this chapter, the scope and limitations of cross-coupling reactions involving organomagnesium reagents are showcased with select examples from the recent literature with a special focus on functional-group-tolerant procedures. The recent developments of the most challenging transformations including either the use of oligofunctional metallic species or β-hydrogen-containing nucleophiles will be specially highlighted.

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“…[160] Die Acylierung des intermediären Grignard-Reagens 177 mit Pivaloylchlorid liefert das 2,3,4-trisubstituierte Chinolinderivat 178 in 84 % Ausbeute. [160] Magnesiertes 176 wurde mit Ethylpinacolboran [161] zu dem Boronsäureester 179 umgesetzt (71 % Ausbeute). Eine Negishi-Kreuzkupplung von 179 mit PhZnCl führt zu dem Kreuzkupplungsprodukt 180 in 76 % Ausbeute.…”

Section: Tmpmgcl·licl Und Verwandte Magnesiumbasenunclassified

“…Eine Negishi-Kreuzkupplung von 179 mit PhZnCl führt zu dem Kreuzkupplungsprodukt 180 in 76 % Ausbeute. [160] Das Chinolinderivat 181 wurde nach der Oxidation der Boronsäure 180 mit 30 %-iger wässriger H 2 O 2 -Lçsung in 89 % Ausbeute erhalten. Amidierung von 181 mit (S)-1-Phenylpropylamin liefert den NK3-Rezeptor-Antagonisten Talnetant(182), der von GlaxoSmithKline entwickelt wurde (84 % Ausbeute; Schema 35).…”

Section: Tmpmgcl·licl Und Verwandte Magnesiumbasenunclassified

“…Amidierung von 181 mit (S)-1-Phenylpropylamin liefert den NK3-Rezeptor-Antagonisten Talnetant(182), der von GlaxoSmithKline entwickelt wurde (84 % Ausbeute; Schema 35). [160] Die N,N,N',N'-TetramethyldiaminophosphordiamidatGruppe [162] ist aufgrund der außergewçhnlichen Polarität der P = O-Bindung eine sehr stark dirigierende Gruppe. Die Knüpfung dieser Funktionalität an vielfältige N-Heterocyclen, die eine Hydroxyfunktion tragen, führt zu glatten Magnesierungen.…”

Section: Tmpmgcl·licl Und Verwandte Magnesiumbasenunclassified

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Regio‐ und chemoselektive Metallierung von Arenen und Heteroarenen mit gehinderten Metallamidbasen

et al. 2011

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Die Synthese hoch funktionalisierter Organometallverbindungen gelingt durch C‐H‐Aktivierung zahlreicher ungesättigter Substrate mit Lithiumchlorid‐solubilisierten 2,2,6,6‐Tetramethylpiperidyl‐Basen (TMPnMXm⋅p LiCl). Diese Reagentien erweisen sich als exzellent zur Umwandlung vielfältiger aromatischer sowie heterocyclischer Substrate in nützliche metallorganische Reagentien mit weiter Anwendungsbreite in der organischen Synthese.

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Multiple Regioselective Functionalizations of Quinolines via Magnesiations

Cited by 90 publications

References 26 publications

Review. Regioselective Functionalization of Pyridines using a Directed Metalation or a Halogen/Metal Exchange

Review. Regioselective Functionalization of Pyridines using a Directed Metalation or a Halogen/Metal Exchange

Carbon–Carbon‐Bond‐Forming Reactions Mediated by Organomagnesium Reagents

Regio‐ und chemoselektive Metallierung von Arenen und Heteroarenen mit gehinderten Metallamidbasen

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