The directed ortho metalation–transition metal–catalyzed reaction symbiosis in heteroaromatic synthesis

Chauder, Brian A.; Green, Laine; Snieckus, Victor

doi:10.1351/pac199971081521

Cited by 40 publications

(18 citation statements)

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“…[8,9] The functional group serves to direct the lithiation either electronically or by coordination. However, there are a few reported cases of direct lithiation of unsubstituted electron-deficient heterocycles.…”

Section: Resultsmentioning

confidence: 99%

Symmetric and Asymmetric Coupling of Pyridylpyrimidine for the Synthesis of Polynucleating Ligands

Polson

Lotoski

Johansson

et al. 2002

Eur. J. Inorg. Chem.

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Section: Resultsmentioning

confidence: 99%

Symmetric and Asymmetric Coupling of Pyridylpyrimidine for the Synthesis of Polynucleating Ligands

Polson

Lotoski

Johansson

et al. 2002

Eur. J. Inorg. Chem.

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“…A1 reacts faster with PhH 2 SiOR than with PhSiH 3 on account of a complex-induced proximity effect (CIPE). [13] Further conversion of PhHSi(OR) 2 to PhSi(OR) 3 is likely hindered for steric reasons.…”

Section: Catalytic Hydrosilylation Of Ketonesmentioning

confidence: 99%

Reduction of Ketones with Hydrocarbon‐Soluble Calcium Hydride: Stoichiometric Reactions and Catalytic Hydrosilylation

2008

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Reactions of the dimeric calcium hydride complex[(DIPP‐nacnac)CaH·thf]2 {1; DIPP‐nacnac = CH[(CMe)(2,6‐iPr2C6H3N)]2} with the α‐hydrogen containing ketones acetophenone, acetone, dibenzylketone and 2‐adamantone are smooth. In most cases not only addition but also substantial enolization is observed as a side reaction and in some cases also aldol condensation was found. Despite this unselectivity, the addition products could be isolated crystalline pure. Crystal structures of [(DIPP‐nacnac)CaOCH(Me)Ph]2 (3), [(DIPP‐nacnac)CaOCH(CH2Ph)2]2 (6) and [(DIPP‐nacnac)Ca(2‐adamantoxide)]2 (7) have been determined. The calcium hydride complex 1 is an effective catalyst in the hydrosilylation of ketones. Independent from the silane/ketone ratio, a strong preference for formation of bis‐alkoxy silanes [PhSiH(OR)2] is observed. In most cases no enoxy groups have been found in the product. This indicates that the mechanism does not involve addition of the calcium hydride to the ketone functionality. A concerted addition of silane to ketone through a six‐coordinate hypervalent silicon intermediate is proposed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

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“…Thus, benzamides can also undergo ortho-metalation [181,[217][218][219][220][221][222] or metalation at benzylic positions [223][224][225]. Thus, benzamides can also undergo ortho-metalation [181,[217][218][219][220][221][222] or metalation at benzylic positions [223][224][225].…”

Section: A-nitrogen Carbanionsmentioning

confidence: 99%

“…Arenes cannot usually be deprotonated with LDA alone, but require mixtures of organosodium [365] or organolithium compounds and tertiary amines [181,218,219]. These amines, for instance TMEDA, lead to a partial dissociation of oligomeric BuLi-solvent aggregates and thereby to more powerful metalating reagents [366,367].…”

Section: Aromatic Carbanionsmentioning

confidence: 99%

The Alkylation of Carbanions

Dörwald

2004

Side Reactions in Organic Synthesis

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The deprotonation of organic compounds by strong, non-nucleophilic bases followed by C-alkylation with a suitable electrophile has become one of the most predictable and straightforward methods for formation of C-C bonds. The popularity of this chemistry is also a consequence of the often-seen close resemblance of feasible structural modifications by a deprotonation/alkylation strategy to an unsophisticated retrosynthetic analysis of a given target compound. Other reactions, which involve, for instance, substantial rearrangement of the carbon framework (e.g. Cope rearrangement, fragmentations, ring contractions or enlargements) are usually more difficult to take into account during retrosynthetic analysis.LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2]. Because the reactivity of an organometallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles.In this chapter the alkylation of carbanions with simple carbon electrophiles will be discussed, with special emphasis on the structure-reactivity relationship of the carbanion and on side reactions. In this context the term "carbanion" refers to an intermediate prepared by in-situ deprotonation of an organic compound, followed by optional cation exchange (transmetalation), which tends to be alkylated at carbon by soft electrophiles such as MeI or PhCHO. This type of reactivity is characteristic of enolates with an ionic M-O bond or for organometallic compounds with a strongly polarized or ionic M-C bond, M typically being an alkali metal, Mg, Cu, or Zn. Carbanions can, alternatively, also be prepared by halogen-metal exchange [3-8], sulfoxide-or sulfone-metal exchange [9-13], or by transmetalation of stannanes. The most suitable reagents for performing such metalating exchange reactions are organometallic compounds with a metal-bound secondary or tertiary alkyl group, such as tBuLi, sBuLi, iPr 2 Zn [14, 15], or iPrMgHal [6]. These reagents are thermodynamically less stable than organometallic compounds with primary alkyl 5 146 Scheme 5.1. Approximate relative rates of proton transfer in water at thermoneutrality (DpK a = 0) [35, 39, 51]. 147 Scheme 5.2. The effect of fluorine on the acidity of organic compounds [24, 62-65]. 148 Scheme 5.3. Dependence of the reactivity of carbanions on their basicity [68, 72-74]. Regioselectivity of Deprotonations and AlkylationsThe organic chemist is occasionally confronted with the problem that a compound has several differrent X-H groups of similar pK a . If only one of these is to be alkylated, one option would be to perform a regioselective deprotonation. This can sometimes be achieved by exploiting small differences be...

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The directed ortho metalation–transition metal–catalyzed reaction symbiosis in heteroaromatic synthesis

Cited by 40 publications

References 1 publication

Symmetric and Asymmetric Coupling of Pyridylpyrimidine for the Synthesis of Polynucleating Ligands

Symmetric and Asymmetric Coupling of Pyridylpyrimidine for the Synthesis of Polynucleating Ligands

Reduction of Ketones with Hydrocarbon‐Soluble Calcium Hydride: Stoichiometric Reactions and Catalytic Hydrosilylation

The Alkylation of Carbanions

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