First metalation of aryl iodides: directed ortho-lithiation of iodopyridines, halogen-dance, and application to synthesis

Rocca, Patrick; Cochennec, C.; Marsais, Francis; Thomas‐Dit‐Dumont, L.; Mallet, M.; Godard, Alain; Quéguiner, G.

doi:10.1021/jo00079a031

Cited by 128 publications

(61 citation statements)

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“…2-Iodopyridine, [25] 3-iodopyridine, [25] 4-iodopyridine, [26] 2-chloro-3-iodopyridine, [27] 2-chloro-4-iodopyridine, [28] 5-bromo-2-iodopyridine, [29] 2-bromo-6-iodopyridine [25] and 2,3,5-tribromopyridine [30] were prepared according to literature procedures.…”

Section: Methodsmentioning

confidence: 99%

Trifluoromethyl-Substituted Pyridines Through Displacement of Iodine by in situ Generated (Trifluoromethyl)copper

2002

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Section: Methodsmentioning

confidence: 99%

Trifluoromethyl-Substituted Pyridines Through Displacement of Iodine by in situ Generated (Trifluoromethyl)copper

2002

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“…Several synthetically useful base-promoted halogen displacements have previously been reported in the area of five-membered and six-membered heterocycles. 5-Bromo-3-methylisothiazole, [45] 5-bromo-3-methyl-1-phenylpyrazole, [46] 2-bromo-5-methylthiophene, [47Ϫ49] 2,3-dibromothiophene, [50Ϫ53] 2,5-dibromothiophene, [54] 2,3,5-tribromothiophene, [55] 2-bromo-5-methylfuran, [56,57] 2,3-and 2,5-dibromofuran, [56,57] 3-bromo-2-fluoropyridine, [58] 3-bromo-2-chloropyridine, [59] 3-fluoro-4-iodopyridine, [59] 2-chloro-3-fluoro-4-iodopyridine, [59] and 3-fluoro-4-iodoquinoline [60] have all been found to isomerize cleanly after metalation.…”

Section: Halogen Shufflingmentioning

confidence: 99%

The Organometallic Approach to Molecular Diversity − Halogens as Helpers

Schlosser

2001

Eur. J. Org. Chem.

103

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“…Under thermodynamic conditions, a multistep process affords the most stable lithium intermediate, which is trapped by the electrophile producing an unprecedented selectivity. The reaction was next applied to iodine [72] as well as to quinolines [73] (Scheme 15.14). Besides the original regioselective derivatizations, HD allows isomerizations after the final hydrolytic step.…”

Section: Halogen Dance: a Useful Side Reactionmentioning

confidence: 99%

“…Moreover, when intramolecular halogen-lithium permutation can occur, halogen migration could be observed to provide more stable lithio species which are otherwise difficult to access. Such a halogen dance reaction [69,72] has been proven to be a useful synthetic tool and opens the scope of versatile heterocyclic functionalization. An application of this synthetic method is reported in Scheme 15.30 outlining the synthesis of Mappicine [111].…”

Section: Miscellaneous Examples Of Various Heteroaryllithium Reagentsmentioning

confidence: 99%

Lithiated Aza‐Heterocycles in Modern Synthesis

Fort

Comoy

2014

Lithium Compounds in Organic Synthesis

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Introduction Functional nitrogen-containing heteroaromatic compounds, especially sixmembered ones (pyridines, diazines, quinolines, and their fused derivatives), have attracted the attention of chemists worldwide because they play an important role in the development of new pharmaceuticals [1], agrochemicals [2], catalysts [3], or materials [4] (including polymers).Besides the classical reactions (i.e., electrophilic heteroaromatic substitutions on heterocycles or single electron-transfer (SET) mediated reactions with brominated derivatives) [5] and ex nihilo ring syntheses [6], metallation reactions providing organolithium compounds are of particular interest because they allow the direct functionalization starting from bare or sparsely substituted heterocycles intrinsically more acidic than similar benzene-ring systems. However, the strong bases used for metallation as well as the prepared organolithiums also exhibit a large propensity for nucleophilic addition. Further, though numerous methods have been described for the single derivatization, multiple functionalization often appears much more sensitive and difficult because of the complexation or aggregation phenomena observed either with primary substituents or with the nitrogen atom in the heterocycle itself. These complex phenomena, together with the variation in reaction conditions (temperature, solvent, ratio), produce various competitive reaction pathways. Thus, an arsenal of methodologies has then been developed to tune the regio-, chemio-, and sometimes stereoselectivities. The goal is generally to control these additional influences, providing variation of kinetic or thermodynamic acidity at various sites susceptible to lithiation.With a special focus on pyridines, quinolines, diazines, and fused pyridinic compounds, this chapter describes organolithium tools that allow (i) direct derivatization of bare N-containing heteroaromatics; (ii) metallation of dipolar adducts of pyridines and analogs; (iii) halogen/Li exchanges; (iv) ring metallation by using directing metallation groups; (v) lithiation invoking an halogen dance; and (vi) lateral and remote lithiations (Scheme 15.1). Next, the usefulness of these tools, often Lithium Compounds in Organic Synthesis: From Fundamentals to Applications, First Edition. Edited by Renzo Luisi and Vito Capriati.

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First metalation of aryl iodides: directed ortho-lithiation of iodopyridines, halogen-dance, and application to synthesis

Cited by 128 publications

References 0 publications

Trifluoromethyl-Substituted Pyridines Through Displacement of Iodine by in situ Generated (Trifluoromethyl)copper

Trifluoromethyl-Substituted Pyridines Through Displacement of Iodine by in situ Generated (Trifluoromethyl)copper

The Organometallic Approach to Molecular Diversity − Halogens as Helpers

Lithiated Aza‐Heterocycles in Modern Synthesis

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