Palladium-Catalyzed, Ligand-Free Suzuki Reaction in Water Using Aryl Fluorosulfates

Liang, Qiaobin; Xing, Peng; Zhi-jian, Huang; Dong, Jiajia; Sharpless, K. Barry; Li, Xiaoxian; Jiang, Biao

doi:10.1021/acs.orglett.5b00654

Cited by 137 publications

(55 citation statements)

References 50 publications

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“…Suzuki-Miyaura coupling is one of the powerful and convenient approach for C(sp 2 )−C(sp 2 ) bond formation, as it has the properties of mild reaction conditions, high tolerance toward functional groups, high stability, and wide diversity of commercially available boronic acids. [40] Inspired by this work, we explored the reaction conditions using HP-ArOFs-1 and boronic acid KB1 as model substrates, and palladium(II)acetate as catalyst. [48][49][50] In particular, Jiang's lab reported the palladium-catalyzed cross-coupling reaction with aryl boronic acids, which was carried out in water at room temperature with excellent yields.…”

Section: Resultsmentioning

confidence: 99%

DNA‐Encoded Libraries: Aryl Fluorosulfonates as Versatile Electrophiles Enabling Facile On‐DNA Suzuki, Sonogashira, and Buchwald Reactions

Wang

et al. 2019

Advanced Science

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are encoded by unique DNA sequences as identification "barcodes," and are assembled combinatorial using split-andpool strategy or alternative procedures via DNA-compatible reactions. [7][8][9] DELs comprising millions or even billions of DNA-tagged druglike molecules can be effectively synthesized via this technology and screened against various protein targets of interest in a single pooled assay. In a typical affinity-based selection experiment, when non-and low-affinity binders are washed away, the DNA tag of the remaining compounds can be amplified using polymerase chain reaction and the relative frequency of the remaining compounds before and after selection is determined by counting the number of DNA tags in high-throughput DNA sequencing experiments. [10,11] To date, a large number of high-quality hits have been identified by the DEL technology for various therapeutically relevant targets, such as kinases, [12] phosphatases, [13] and G-protein coupled receptors. [14] Several drug candidates derived from their corresponding DEL hits, such as soluble epoxide hydrolase inhibitor GSK2256294, and death domain receptor-associated adaptor kinase RIP1 inhibitor GSK2982772 have progressed to latestage clinical development, [15,16] further emphasizing DEL as a powerful technology for small molecular drug discovery.Despite these successes, the great potential of DEL technology in drug discovery has not yet been fully realized. One of the most fundamental challenges is the synthesis of high-quality libraries with more structural diversity, which in turn depends on the development of new and robust DNA-compatible reactions that allow more flexibility in DEL's design and synthesis. Among various DNA-compatible reactions developed in recent years, transition-metal-promoted reactions such as Suzuki-Miyaura coupling, [17][18][19][20][21][22][23] Sonogashira coupling, and Buchwald-Hartwig amination using DNA-conjugated aryl halides as electrophiles have been elegantly developed (Figure 1), [24][25][26] and some of them have been developed for DEL synthesis. However, the environmental toxicity and high costs of aryl halides have hindered their large-scale applications in industry. Thus, much attention has been paid to phenol-derived electrophiles recently, [27] which, as compared to aryl halides, offer a more sustainable starting material because most of them are readily available from biomass. [28] In addition, phenol modules are also important components of natural products (NPs), bioactive molecules, and pharmaceutical drugs. Coupling reactions with Using (hetero)aryl fluorosulfonates as versatile electrophiles, facile on-DNA cross-coupling reactions of Suzuki, Sonogashira, and Buchwald are reported here. Notably, all of these reactions show excellent functional group tolerance, mild reaction conditions (relative low temperature and open to air), rich heterocyclic coupling partners, and more importantly, DNA-compatibility. Thus, these new reactions based on efficient formation of C(sp 2 )-C(sp 2 ), C(sp 2 )-C(sp), and C(s...

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Section: Resultsmentioning

confidence: 99%

DNA‐Encoded Libraries: Aryl Fluorosulfonates as Versatile Electrophiles Enabling Facile On‐DNA Suzuki, Sonogashira, and Buchwald Reactions

Wang

et al. 2019

Advanced Science

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“…[16] The efficient Suzuki cross couplings of aryl fluorosulfates with aryl boronic acids was subsequently disclosed in early 2015, [17] demonstrating the –OSO 2 F group as atom efficient and economically viable alternative to triflate. [18] More recently, Hanley [19] and coworkers published a study on how the fluorosulfate handle fits into the hierarchy of leaving group in Suzuki aryl couplings.…”

Section: Introductionmentioning

confidence: 99%

Chemoselective Synthesis of Polysubstituted Pyridines from Heteroaryl Fluorosulfates

Zhang¹,

Tang²,

et al. 2016

Chemistry A European J

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A selection of heteroaryl fluorosulfates were readily synthesized using commercial SO2F2 gas. These substrates are highly efficient coupling partners in the Suzuki reaction. Through judicious selection of Pd-catalysts, the fluorosulfate functionality is differentiated from bromide and chloride; the order of reactivity being: -Br > -OSO2F > -Cl. Exploiting this trend allowed the stepwise chemoselective synthesis of a number of polysubstituted pyridines, including the drug, Etoricoxib.

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“…[36][37][38][39][40] In 1989, Bumagin et al 57 were the first to report a Pd(OAc) 2 catalyzed Suzuki reaction of phenylboronic acid with aryl iodides containing a -OH or -COOH substituents; Na 2 CO 3 was employed as the base in neat water under an argon atmosphere. Later, a series of academic papers [58][59][60][61][62][63][64][65][66][67][68][69] reported palladium-catalyzed Suzuki couplings of various aryl and allylic halides (I, Br, Cl) with no added ligand or additives in hot water. Excellent yields (up to 99%) of cross-coupling products were reported.…”

Section: Introductionmentioning

confidence: 99%

“…[57][58][59][60][61][62][63][64][65][66][67][68][69] In addition, a clear answer has not been provided on whether the current ligand-free/aqueous protocols are effective for the Suzuki couplings of 6 unprotected basic nitrogen containing substrates at scales greater than a few milliliters. Herein, we report 100-mL scale palladium-catalyzed Suzuki reactions with no added ligand in neat water involving four model substrates, three of which contain basic nitrogen centers.…”

Section: Introductionmentioning

confidence: 99%

Palladium-Catalyzed Suzuki Reactions in Water with No Added Ligand: Effects of Reaction Scale, Temperature, pH of Aqueous Phase, and Substrate Structure

Zhao

Gelbaum

Heaner

et al. 2016

Org. Process Res. Dev.

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The heterogeneous palladium-catalyzed Suzuki reactions between model aryl bromides (4-bromoanisole, 4-bromoaniline, 4-amino-2-bromopyridine, and 2-bromopyridine) and phenylboronic acid have been successfully conducted in water with no added ligand at the 100-mL scale using 20-40 millimoles of aryl bromide. The product yields associated with these substrates were optimized and key reaction parameters affecting the yields were identified. The results clearly indicate that the reaction parameters necessary to achieve high yields are substrate dependent. In addition, it is demonstrated that aqueous Suzuki reactions of substrates containing basic nitrogen centers can produce quantitative yields of desired products in the absence of added ligand.KEYWORDS: palladium catalysis without added ligand, Suzuki reactions in water, heterogeneous catalysis, scale-up, green and sustainable Suzuki reactions.

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Palladium-Catalyzed, Ligand-Free Suzuki Reaction in Water Using Aryl Fluorosulfates

Cited by 137 publications

References 50 publications

DNA‐Encoded Libraries: Aryl Fluorosulfonates as Versatile Electrophiles Enabling Facile On‐DNA Suzuki, Sonogashira, and Buchwald Reactions

DNA‐Encoded Libraries: Aryl Fluorosulfonates as Versatile Electrophiles Enabling Facile On‐DNA Suzuki, Sonogashira, and Buchwald Reactions

Chemoselective Synthesis of Polysubstituted Pyridines from Heteroaryl Fluorosulfates

Palladium-Catalyzed Suzuki Reactions in Water with No Added Ligand: Effects of Reaction Scale, Temperature, pH of Aqueous Phase, and Substrate Structure

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