Metalation of Aryl Iodides, Part II: Directed Ortho-Lithiation of 3-Iodo-N,N-diiospropyl-2-pyridinecarboxamide: Halogen-Dance and Synthesis of an Acyclic Analogue of Meridine

Cochennec, C.; Rocca, Patrick; Marsais, Francis; Godard, Alain; Quéguiner, G.

doi:10.1055/s-1995-3896

Cited by 31 publications

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“…It is well-known that strong bases such as lithium amide − or organolithium − abstract protons from azines to give the corresponding organolithium species. It is notable that C–H acidity was calculated and the relationship with regioselectivity was nicely summarized. − For example, Quéguiner and co-workers reported C3-lithiation of 2-methoxypyridine in the presence of a catalytic amount of secondary amine (Scheme ).…”

Section: Deprotonative Metalation Of Azines −mentioning

confidence: 99%

C–H Functionalization of Azines

et al. 2017

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Azines, which are six-membered aromatic compounds containing one or more nitrogen atoms, serve as ubiquitous structural cores of aromatic species with important applications in biological and materials sciences. Among a variety of synthetic approaches toward azines, C-H functionalization represents the most rapid and atom-economical transformation, and it is advantageous for the late-stage functionalization of azine-containing functional molecules. Since azines have several C-H bonds with different reactivities, the development of new reactions that allow for the functionalization of azines in a regioselective fashion has comprised a central issue. This review describes recent advances in the C-H functionalization of azines categorized as follows: (1) SAr reactions, (2) radical reactions, (3) deprotonation/functionalization, and (4) metal-catalyzed reactions.

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Section: Deprotonative Metalation Of Azines −mentioning

confidence: 99%

C–H Functionalization of Azines

et al. 2017

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“…Metalated oxazoles, indoles, or furans can, however, be unstable and undergo ring-opening reactions [179,181,388]. Pyridines and other six-membered, nitrogen-containing heterocycles can also be lithiated [59,370,[390][391][392][393][394][395][396][397][398] or magnesiated [399], but because nucleophilic organometallic compounds readily add to electron-deficient heteroarenes, dimerization can occur, and alkylations of such metalated heteroarenes often require careful optimization of the reaction conditions [368,400,401] (Schemes 5.42 and 5.69). 176 Scheme 5.41.…”

Section: Aromatic Carbanionsmentioning

confidence: 99%

“…Because of their inherent instability, however, metalated halo-or trihalomethyl arenes should be handled with great care, especially when performing reactions on a large scale. Iodoarenes have also been metalated, but migration of iodine ("halogen dance") is often observed [398]. ortho-Lithiated bromoor chlorobenzene undergo b-elimination even at temperatures slightly above -100 C [412], but some polyhalogenated aryllithium compounds are significantly more stable (Scheme 5.45).…”

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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“…Recent results [9d, 41], have pointed to the additional feature of the ''halogen dance'' as a tool for the construction of unusually substituted pyridines. Illustrative are the conversion of 69 into 2,3,4-substituted pyridines 70 and, more interestingly, of 71 into the tetrasubstituted 72 bearing all but one of the theoretically possible halogens (Scheme 24) [42].…”

Section: Pyridinesmentioning

confidence: 99%

The Directed ortho Metalation Reaction – A Point of Departure for New Synthetic Aromatic Chemistry

Hartung

Snieckus

2002

Modern Arene Chemistry

160

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After a brief allusion to the current status of synthetic aromatic chemistry, a tour based on the Directed ortho Metalation (DoM) strategy is provided with selections from recent literature which highlight a) the use of DoM for the regiospecific preparation of polysubstituted aromatics and heteroaromatics; b) the valuable symbiosis of DoM with transition metal catalyzed AraAr cross-coupling protocols; c) the extension of DoM to the Directed remote Metalation (DreM) concept in biaryls, which provides methodologies for the construction of condensed aromatics (fluorenones, phenanthrols) and heterocyclics (thioxanthones, xanthones, acridones, dibenzphosphorinones, dibenzthiepinone dioxides, dibenzoxepinones, dibenzazepinones, dibenzphosphinones); and d) the evolving links of DoM to other modern methodologies with a note on the DoM-Grubbs ring-closing metathesis connection. The presentation is solely methodologically rather than total synthesis oriented; dependable directed metalation groups (DMGs ¼ CONR 2 , OCONR 2 , SONR 2 , NHBoc), new and renewed, are emphasized; p-excessive (furan, thiophene, indole) and p-deficient (pyridine) heterocycle HetDoM chemistry is delineated. While definitely not comprehensive, this account attempts to give a flavor of current anionic aromatic chemistry in synthesis. 10.1Scheme 1. Synthetic approaches to substituted aromatics. 10.2 The DoM Reaction as a Methodological Tool 331 Scheme 3. DoM chemistry generalizations. 10.2 The DoM Reaction as a Methodological Tool 333 Scheme 5. The N-cumyl sulfonamide DMG. Scheme 6. The N-cumyl carbamate DMG. 10.2 The DoM Reaction as a Methodological Tool 335 Scheme 9. The di-tert-butyl phosphine oxide DMG. 10.3 Heteroaromatic Directed ortho Metalation (HetDoM) in Methodological Practice 337

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Metalation of Aryl Iodides, Part II: Directed Ortho-Lithiation of 3-Iodo-N,N-diiospropyl-2-pyridinecarboxamide: Halogen-Dance and Synthesis of an Acyclic Analogue of Meridine

Cited by 31 publications

References 0 publications

C–H Functionalization of Azines

C–H Functionalization of Azines

The Alkylation of Carbanions

The Directed ortho Metalation Reaction – A Point of Departure for New Synthetic Aromatic Chemistry

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