Hiyama Cross-Coupling of Chloro-, Fluoro-, and Methoxypyridyltrimethylsilanes: Room-Temperature Novel Access to Functional Bi(het)aryl

Pierrat, Philippe; Gros, P.; Fort, Yves

doi:10.1021/ol047482u

Cited by 128 publications

(49 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[24] This seems quite challenging because unactivated trialkylsilyl groups are usually poorly reactive, and besides, Hiyama couplings of silylated pyridines are rare. [25] In view of the recent work of Philippe Gros and co-workers, who showed that the incorporation of chloro, fluoro, or methoxy substituents on the pyridine ring of pyridyltrimethylsilanes allows efficient Hiyama cross-couplings, [25a] we reasoned that our products, which bear a nitrogen substituent, could also be valuable partners for such transformations. Gratifyingly, under the same experimental procedure, we were able to substitute the trimethylsilyl group by a p-methoxybenzene group in good yield (Scheme 7).…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular Co^I‐Catalyzed [2+2+2] Cycloaddition between Ynamides, Nitriles, and Alkynes

Garcia

Moulin

Miclo

et al. 2009

Chemistry A European J

View full text Add to dashboard Cite

Three-ring circus: An expedient route to tricyclic fused 2-trimethylsilyl-3-aminopyridines exhibiting unprecedented skeletons is described. The key step is a very efficient cobalt-catalyzed [2+2+2] cycloaddition of a polyunsaturated compound displaying an ynamide, an alkyne, and a nitrile functionality (see picture). The first [2+2+2] cocyclizations between ynamides, nitriles, and alkynes are reported. They open a new access to unprecedented nitrogen-containing heterocycles of type 2-trimethylsilyl-3-aminopyridines. Such frameworks, which can be found in various compounds of biological interest, are very difficult to prepare by conventional methods. However, using [CpCo(C(2)H(4))(2)] (Cp=cyclopentadienyl) as catalyst, the intramolecular cyclizations could be achieved in up to 100 % yield. The presence of the trimethylsilyl group allowed a rare type of Hiyama cross-coupling: one of the silylated pyridines could be coupled with p-iodoanisole to give a new type of biaryl system.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular Co^I‐Catalyzed [2+2+2] Cycloaddition between Ynamides, Nitriles, and Alkynes

Garcia

Moulin

Miclo

et al. 2009

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…TBAF, THF], 75% conversion of the starting material was observed (Table 1, entry 1). However, surprisingly, the major product turned out to be the C-3 methoxylated pyrazinone and only 35% of the expected C-3 arylated compound was observed.[11] To our satisfaction we found that addition of CuI [12] effectively suppressed the formation of 4a, hence acting as a reaction switch between methoxylated and arylated products. After extensive investigation of the reaction parameters, we found that 1.5 equiv.…”

mentioning

confidence: 79%

Palladium‐Catalyzed Desulfitative CC Cross‐Coupling Reaction of (Hetero)Aryl Thioesters and Thioethers with Arylsiloxanes

2008

View full text Add to dashboard Cite

Abstract:The first desulfitative Hiyama-type crosscoupling protocol is reported and exemplified by the synthesis of substituted 5-chloro-3-arylpyrazinones. The method has also been successfully applied for the arylation of other (hetero)aryl thioethers and thioesters.Keywords: copper(I); cross-coupling; desulfitative procedure; Hiyama reaction; homogeneous catalysis; pyrazinones Palladium-catalyzed C À C and C À heteroatom bondforming cross-coupling reactions are among the most powerful methods in organic synthesis.[1] Such procedures involve the coupling of an activated electrophilic partner with a nucleophilic organometallic donor through a palladium-assisted cross-coupling cascade. For this purpose a number of organometallic donors have been explored, mainly organoborons, [2] organostannanes, [3] and organozinc reagents. [4] Seminal work by Liebeskind and co-workers describes the coupling of aryl or heteroaryl thioethers with organoboron, organotin or organoindium compounds.[5] However instability, difficulty in preparation and, most importantly, toxicity of most organometallic reagents keep chemists searching for alternatives. Hiyama demonstrated the potential of the use of organosilicon reagents as nucleophilic coupling partners having the advantage of being environmentally safe and posing no toxicity hazards.[6] Since then, an increasing number of publications has appeared dealing with the coupling of activated (hetero)aromatic systems with organosilicon reagents, applying this Hiyama protocol. [7] Denmark et al. have successfully applied a variety of silanols as active transmetallating species. [8] However, nearly all Hiyama protocols have focused on the coupling of C À X electrophiles, X being halide or triflate. Until now, we are unaware of any example of Hiyama coupling with activated C sp 2 À S electrophiles. Pursuant to our long-standing interest in the synthesis and decoration of the pyrazin-2(1H)-one scaffold [9] and to our recently described protocol for the transition metal-catalyzed orthogonal decoration of the 2(1H)-pyrazinone scaffold using a sulfur linker, [10] we were keen to investigate whether a desulfitative Hiyama-type reaction at the C-3 position of 5-chloro-3-(phenylsulfanyl)pyrazin-2(1H)-ones would be possible. Tests were performed with 5-chloro-1-(4-methoxybenzyl)-3-(phenylsulfanyl)pyrazin-2(1H)-one (1a) and trimethoxyphenylsilane as a model system. Applying the standard conditions for the Hiyama process [5 mol% Pd(II), 10 mol% ligand, 2 equiv. TBAF, THF], 75% conversion of the starting material was observed (Table 1, entry 1). However, surprisingly, the major product turned out to be the C-3 methoxylated pyrazinone and only 35% of the expected C-3 arylated compound was observed.[11] To our satisfaction we found that addition of CuI [12] effectively suppressed the formation of 4a, hence acting as a reaction switch between methoxylated and arylated products. After extensive investigation of the reaction parameters, we found that 1.5 equiv. of phenyltrimethoxysilane 2a, 5 mol% of PdA C...

show abstract

“…For example, even hindered trimethylsilyl groups do not inhibit the metallation and can act as a temporary protecting group useful to obtain the regiochemically exhaustive substitution of heterocycles (Scheme 15.12) [66]. The deprotection is obtained by classical protodesilylation or reduction, as silylated intermediates can also serve in Hiyama reactions [67]. Most used in aromatic series, sulfonamide, O-sulfamate, O-carbamate, N-cumyl sulfonamide, or arylsulfoxide groups can also be envisioned as temporary DoM substituents [68].…”

Section: Directed Ortho-metallation (Dom) Of Aza-heterocyclesmentioning

confidence: 99%

Lithiated Aza‐Heterocycles in Modern Synthesis

Fort

Comoy

2014

Lithium Compounds in Organic Synthesis

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Hiyama Cross-Coupling of Chloro-, Fluoro-, and Methoxypyridyltrimethylsilanes: Room-Temperature Novel Access to Functional Bi(het)aryl

Cited by 128 publications

References 18 publications

Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular Co^I‐Catalyzed [2+2+2] Cycloaddition between Ynamides, Nitriles, and Alkynes

Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular Co^I‐Catalyzed [2+2+2] Cycloaddition between Ynamides, Nitriles, and Alkynes

Palladium‐Catalyzed Desulfitative CC Cross‐Coupling Reaction of (Hetero)Aryl Thioesters and Thioethers with Arylsiloxanes

Lithiated Aza‐Heterocycles in Modern Synthesis

Contact Info

Product

Resources

About

Hiyama Cross-Coupling of Chloro-, Fluoro-, and Methoxypyridyltrimethylsilanes: Room-Temperature Novel Access to Functional Bi(het)aryl

Cited by 128 publications

References 18 publications

Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular CoI‐Catalyzed [2+2+2] Cycloaddition between Ynamides, Nitriles, and Alkynes

Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular CoI‐Catalyzed [2+2+2] Cycloaddition between Ynamides, Nitriles, and Alkynes

Palladium‐Catalyzed Desulfitative CC Cross‐Coupling Reaction of (Hetero)Aryl Thioesters and Thioethers with Arylsiloxanes

Lithiated Aza‐Heterocycles in Modern Synthesis

Contact Info

Product

Resources

About

Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular Co^I‐Catalyzed [2+2+2] Cycloaddition between Ynamides, Nitriles, and Alkynes

Synthesis of Tricyclic Fused 3‐Aminopyridines through Intramolecular Co^I‐Catalyzed [2+2+2] Cycloaddition between Ynamides, Nitriles, and Alkynes