Non-cryogenic metalation of aryl bromides bearing proton donating groups: formation of a stable magnesio-intermediate

Katō, Susumu; Nonoyama, Nobuaki; Tomimoto, Koji; Mase, Toshiaki

doi:10.1016/s0040-4039(02)01747-1

Cited by 30 publications

(17 citation statements)

References 12 publications

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“…Scheme 1. As the conventional Friedel-Crafts phthaloylation was feasible only with thiophene derivatives, it was decided to explore other methods [28][29][30][31] that can deliver highly substituted lactones in reasonable yields. We next attempted to prepare the lactones by the magnesio protocol published by Kato et al [32] Notably, different types of lactones were synthesized by metallation of 2-bromobenzoic acid by using a combination of Bu 2 Mg and nBuLi under noncryogenic conditions. By adopting this procedure, lactones 8e-j were synthesized in better yields (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of Benzannelated Thienyl Oligomers

2008

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Section: Resultsmentioning

confidence: 99%

Synthesis and Characterization of Benzannelated Thienyl Oligomers

2008

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“…An iterative building block addition/oxidation/arene‐forming aldol condensation sequence allows an efficient and stereoselective synthesis of oligo‐1,2‐naphthylenes. For an expedient assembly of the oligomer, an organometallic building block with an alkoxide group was used to circumvent protecting group manipulations (Scheme ) …”

Section: Oligo‐12‐naphthylenesmentioning

confidence: 99%

“…For an expedient assembly of the oligomer,a no rganometallic building block with an alkoxide group was used to circumvent protecting group manipulations (Scheme 11). [26] Scheme8.Arene-forming aldol condensation to form configurationally stable aromatic amides.…”

Section: Concept Axially Chiral Aromatic Amidesmentioning

confidence: 99%

Stereoselective Arene‐Forming Aldol Condensation: Catalyst‐Controlled Synthesis of Axially Chiral Compounds

Witzig

Lotter

Fäseke

et al. 2017

Chemistry A European J

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The fundamental role that aldol chemistry adopts in various disciplines, such as stereoselective catalysis or the biosynthesis of aromatic polyketides, illustrates its exceptional versatility. On the one hand, numerous aldol addition reactions reliably transfer the stereochemical information from catalysts into various valuable products. On the other hand, countless aromatic polyketide natural products are produced by an ingenious biosynthetic machinery based on arene-forming aldol condensations. With the aim of complementing aldol methodology that controls stereocenter configuration, we recently combined these two tenets by investigating small-molecule-catalyzed aldol condensation reactions that stereoselectively form diverse axially chiral compounds through the construction of a new aromatic ring.

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“…However, there are also other potential complications. For example, the initially formed intermediate 14 could complex further For other PDG-containing substrates a Japanese group has used the less reactive dibutylmagnesium to effect the initial deprotonation, prior to bromine-lithium exchange, 18 but this suffers from the complication that the waste products of the reaction will contain two different metals, making recovery of the metals more difficult. The same group has also used mesityllithium for initial deprotonation of substrates containing active methylene groups, 19 but mesityllithium is more expensive and less widely available than common organolithium reagents, is more wasteful of organic material, and produces a by-product that is less volatile and more difficult to remove.…”

Section: Scheme 4 Synthesis Of N′-2-(2-bromophenyl)ethyl-nn-dimethylmentioning

confidence: 99%

Lithiation and Substitution of N′-(ω-Phenylalkyl)-N,N-dimethylureas

Smith¹,

El‐Hiti²,

Alshammari³

2012

Synthesis

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Lithiation of N′-phenethyl-N,N-dimethylurea with three equivalents of tert-butyllithium in anhydrous tetrahydrofuran at -78°C takes place on the nitrogen and on the side-chain of the CH 2 next to the phenyl ring (α-lithiation). The 2-lithio isomer can be obtained via bromine-lithium exchange of N′-2-(2-bromophenyl)ethyl-N,N-dimethylurea using methyllithium followed by tertbutyllithium in tetrahydrofuran at -78°C. The lithium reagents thus obtained react with various electrophiles to give the corresponding substituted derivatives in excellent yields. Lithiation of N′-(3-phenylpropyl)-N,N-dimethylurea takes place on the α-CH 2 with tert-butyllithium at 0 °C. On the other hand, lithiation of N′-(4-phenylbutyl)-N,N-dimethylurea with tert-butyllithium at 0 °C takes place on one of the methyl groups of the urea unit.Key words: N′-phenethyl-N,N-dimethylurea, side-chain lithiation, bromine-lithium exchange, electrophile, synthesis Many aromatic compounds undergo lithiation ortho to a functional group, [2][3][4] and the organolithium reagents in such reactions are useful intermediates for the synthesis of ortho-disubstituted aromatics. Moreover, ortho-lithiation has been applied to various heterocycles to produce the corresponding substituted derivatives. 6For example, we have developed several efficient lithiation procedures for preparation of various substituted aromatics and heteroaromatics that might be difficult to prepare by other means. 7As part of such studies we have successfully lithiated and substituted various N-(substituted benzyl)pivalamides and N′-(substituted benzyl)-N,Ndimethylureas selectively using n-butyllithium or tert-butyllithium in tetrahydrofuran. [8][9][10] Such processes have been applied for the production of substituted isoindoline and isoquinoline derivatives. 11-13As part of such studies we became interested in directed lithiation of N′-phenethyl-N,N-dimethylureas. Lithiation of N-phenethylpivalamide derivatives have been reported by Schlosser. 14,15 For example, lithiation of N-phenethylpivalamide itself took place on the side chain (α-lithiation) with three equivalents of tert-butyllithium in tetrahydrofuran at -75 °C. Reaction of the dilithium reagent thus obtained with carbon dioxide, the only electrophile tried, gave the corresponding acid in 72% yield. 14 However, there are no reports of lithiation and substitution of N′-phenethyl-N,N-dimethylureas, and pivalamide and dimethylurea derivatives do not always behave in an identical manner towards lithiation 9 and the urea derivatives are more generally useful for synthesis.We now report the successful lithiation and substitution of N′-phenethyl-N,N-dimethylureas using a simple, general and efficient α-lithiation procedure using tert-butyllithium. We also report a procedure for ring-substitution by Br-Li exchange with methyllithium followed by tert-butyllithium in tetrahydrofuran at -78°C.The first tasks were to synthesise N′-phenethyl-N,N-dimethylurea (2) 16 and to try to find conditions under which its lithiation could ...

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Non-cryogenic metalation of aryl bromides bearing proton donating groups: formation of a stable magnesio-intermediate

Cited by 30 publications

References 12 publications

Synthesis and Characterization of Benzannelated Thienyl Oligomers

Synthesis and Characterization of Benzannelated Thienyl Oligomers

Stereoselective Arene‐Forming Aldol Condensation: Catalyst‐Controlled Synthesis of Axially Chiral Compounds

Lithiation and Substitution of N′-(ω-Phenylalkyl)-N,N-dimethylureas

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