Efficient Synthesis of Substituted Selenophenes Based on the First Palladium(0)‐Catalyzed Cross‐Coupling Reactions of Tetrabromoselenophene

Tùng, Đǎng Thanh; Villinger, Alexander; Langer, Peter

doi:10.1002/adsc.200800316

Cited by 41 publications

(15 citation statements)

References 27 publications

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“…The 3,4‐dibromoselenophene intermediate ( 11 ) cannot be obtained by bromination of selenophene, but it was synthesized by debromination of 2,3,4,5‐tetrabromoselenophene ( 10 ) using Zn and AcOH in water . 2,3,4,5‐Tetrabromoselenophene ( 10 ) was synthesized by bromination of selenophene using CHCl 3 and AcOH as solvent, with dropwise addition of Br 2 . The amount of bromine used and the rate of addition proved to be important for the outcome of this reaction: With large excess of bromine (>4 equiv), 2,3,4,5‐tetrabromoselenophene ( 10 ) was the major product, whereas with less than two equivalents of bromine, 2,5‐dibromoselenophene ( 9 ) could also be obtained in good yield.…”

Section: Resultsmentioning

confidence: 99%

“…[41] 2,3,4,5-Tetrabromoselenophene (10)w as synthesizedb yb romination of selenophene using CHCl 3 and AcOH as solvent, with dropwise addition of Br 2 . [42] The amount of bromine used and the rate of addition proved to be important for the outcomeo ft his reaction:W ith large excess of bromine (> 4equiv), 2,3,4,5tetrabromoselenophene (10)w as the major product, whereas with less than two equivalents of bromine, 2,5-dibromoselenophene (9)c ould also be obtained in good yield. Subsequent cleavage of the methoxyg roups of 3a-d by BBr 3 yielded the desired products 4a-h in 51-68% yields.…”

Section: Chemical Synthesismentioning

confidence: 99%

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Selenophenes: Introducing a New Element into the Core of Non‐Steroidal Estrogen Receptor Ligands

Zhang

Wang

et al. 2017

ChemMedChem

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The importance of the heterocyclic core elements with peripheral phenolic and alkyl substituents as a dominant structural motif of ligands for estrogen receptor (ER) has been well recognized. Here, we expand the structural diversity of core elements by preparing selenium-containing heterocycles and exploring the activities of these selenophenes on the two ERs, ERα and ERβ. Careful structure-activity relationship analysis of their ER binding affinities showed that most selenophenes are ERβ-selective, with the position of the phenol substituents on the selenophenecore and the nature of these substituents having in a marked effect on their binding affinities. The compound bis(2-fluoro-4-hydroxyphenyl)selenophene (2f) has the highest relative binding affinity (RBA) of 24.3 for ERβ. In transcription assays, most of selenophenes exhibit partial to full agonist activity for both ER subtypes, with compounds bis(2-methyl-4-hydroxyphenyl)selenophene (2b), bis(4-fluoro-3-hydroxyphenyl) 3-bromoselenophene (6f), 2,3,5-tris(hydroxyphenyl)-thiophenes (8b and 8d) profiling as superagonists for ERα, but several compounds display a range of ERα or ERβ antagonistic activities. A few selenophenes exhibited antiproliferative activity, with compound 8c showing antiproliferative effects comparable to that of 4OHT in breast cancer MCF-7 cells while being nontoxic to normal VERO cells. These new ligands could act as models for the development of novel agents leading to improved therapeutics that target the estrogen receptor. Add a New Element!Correspondence to: Jian Huang; Hai-Bing Zhou. ‡ These two authors contributed equally to this work Supporting information for this article is given via a link at the end of the document. HHS Public Access Author ManuscriptAuthor Manuscript Author Manuscript Author ManuscriptThis is the first report of selenophene-core compounds as ER ligands. In transcription assays, several selenophenes profiling as superagonists for ERα; moreover, a few selenophenes exhibited antiproliferative activity comparable to that of 4OHT in breast cancer MCF-7 cells while being nontoxic to normal VERO cells. These new ligands could act as models for the development of novel agents leading to improved therapeutics that target the estrogen receptor.

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Section: Resultsmentioning

confidence: 99%

Section: Chemical Synthesismentioning

confidence: 99%

Selenophenes: Introducing a New Element into the Core of Non‐Steroidal Estrogen Receptor Ligands

Zhang

Wang

et al. 2017

ChemMedChem

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“…In 2008, Langer et al. studied the reactivity of 2,3,4,5‐tetrabromoselenophene, which can be obtained in high yield by reaction of selenophene with an excess of bromine (7 equiv) in CH 2 Cl 2 at 0 °C, in Suzuki coupling (Scheme ) . In the presence of 1.3 equiv of arylboronic acids, they obtained the mono‐C2‐arylated 3,4,5‐tribromoselenophene derivatives in 47–68 % yields.…”

Section: C2‐arylation Of Selenophenesmentioning

confidence: 99%

“…In 2008, Langer et al. prepared a variety of 2,3,4,5‐tetraarylselenophenes containing four identical aryl groups via Suzuki coupling, from 2,3,4,5‐tetrabromoselenophene and arylboronic acids (Scheme , top) . They also studied the reactivity of symmetrical 2,5‐diaryl‐3,4‐dibromoselenophenes for access to 2,3,4,5‐tetraarylselenophenes containing different aryl groups (Scheme , middle).…”

Section: C3‐arylation Of Selenophenesmentioning

confidence: 99%

Access to (Hetero)arylated Selenophenes via Palladium‐catalysed Stille, Negishi or Suzuki Couplings or C−H Bond Functionalization Reaction

et al. 2017

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(Hetero)aryl‐substituted selenophenes exhibit important physical properties especially for optoelectronics. Palladium‐catalysed coupling reactions currently represent the most efficient methods to prepare such (hetero)arylated selenophene derivatives. Initially, Stille coupling was the most efficient reaction for the synthesis of these compounds; however, over the last decade, Suzuki coupling has become the most commonly employed. Recently, Pd‐catalysed arylation via the C−H bond activation of selenophenes has proved to be a very convenient alternative method for the preparation of several arylated selenophenes as there is no need to prepare organometallic derivatives. In this Review, the progress and substrate scope in the synthesis of both C2‐ and C3‐arylated selenophenes via Pd‐catalysis are summarized.

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“…5 These were controlled by both electronic and steric factors. We recently reported the methodologies for functionalization of N-methyltetrabromopyrrole, 6 tetrabromothiophene, 6 tetrabromoselenophene 7 and tetrabromofuran, 8 based on site-selective palladium(0)-catalyzed Suzuki reactions. Due to the importance of thieno [3,2-b]thiophene in materials science, we were interested in developing a sequential process for the functionalization of thieno [3,2-b]thiophene via site-selective palladium(0)-catalyzed Suzuki reactions of tetrabromothieno [3,2-b]thiophene with boronic acids.…”

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confidence: 99%

Programmed Synthesis of Tetraarylthieno[3,2-b]thiophene by Site-Selective Suzuki Cross-Coupling Reactions of Tetrabromothieno[3,2-b]thiophene

Nguyen

Tran

et al. 2013

Synlett

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Thieno[3,thiophene is a structural motif that can be found in many important organic materials. A number of mono-, diand tetraarylthieno [3,2-b]thiophenes are reported herein. [1]benzothiophene (C 13 BTBT) were shown to demonstrate a very high thin film mobility of 3.1 cm 2 /Vs and 17.2 cm 2 /Vs, respectively, in VD-OFETs. 4b,c Due to intermolecular sulfur-sulfur interactions, materials containing thieno[3,2-b]thiophene may increase the electronic transport between neighboring molecules. The introduction of substituents into the core structure of materials may change electronic properties, solubility as well as molecular packing. 2m For tuning electronic properties, heterocycles have been widely functionalized by many methods, especially, by palladium(0)-catalyzed cross-coupling reactions. 5 It was previously shown that polyhalogenated heterocycles can be regioselectively functionalized by palladium-catalyzed crosscoupling reactions at the carbon-halogen bonds adjacent to the heteroatom. 5 These were controlled by both electronic and steric factors. We recently reported the methodologies for functionalization of N-methyltetrabromopyrrole, 6 tetrabromothiophene, 6 tetrabromoselenophene 7 and tetrabromofuran, 8 based on site-selective palladium(0)-catalyzed Suzuki reactions. Due to the importance of thieno[3,2-b]thiophene in materials science, we were interested in developing a sequential process for the functionalization of thieno [3,2-b]thiophene via site-selective palladium(0)-catalyzed Suzuki reactions of tetrabromothieno[3,2-b]thiophene with boronic acids. We report herein an efficient synthesis of mono-, di-and tetraarylthieno[3,2-b]thiophene using this strategy.The Suzuki-Miyaura reactions of 1 9 (1.0 equiv) with a series of boronic acids (1.2 equiv) resulted in a site-selective formation of 2-aryl-3,5,6-tribromothieno[3,2-b]thiophenes 2a-j 5 in 25-80% yields (Scheme 1 and Table 1). The conditions used were optimized with regard to temperature, solvent, base additive, and water additive. Pd(PPh 3 ) 4 was found to be an efficient catalyst for the current reaction. Other well-known catalyst systems, such as Pd(OAc) 2 /X-Phos, resulted in lower yields of the desired products. All reactions were carried out at 90-110 °C in 4-6 hours. Table 1).

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Efficient Synthesis of Substituted Selenophenes Based on the First Palladium(0)‐Catalyzed Cross‐Coupling Reactions of Tetrabromoselenophene

Cited by 41 publications

References 27 publications

Selenophenes: Introducing a New Element into the Core of Non‐Steroidal Estrogen Receptor Ligands

Selenophenes: Introducing a New Element into the Core of Non‐Steroidal Estrogen Receptor Ligands

Access to (Hetero)arylated Selenophenes via Palladium‐catalysed Stille, Negishi or Suzuki Couplings or C−H Bond Functionalization Reaction

Programmed Synthesis of Tetraarylthieno[3,2-b]thiophene by Site-Selective Suzuki Cross-Coupling Reactions of Tetrabromothieno[3,2-b]thiophene

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