Chemoselective Synthesis of Polysubstituted Pyridines from Heteroaryl Fluorosulfates

Zhang, En-Xuan; Tang, Jiaze; Li, Suhua; Wu, Peng; Moses, John E.; Sharpless, K. Barry

doi:10.1002/chem.201600167

Cited by 77 publications

(50 citation statements)

References 31 publications

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“…When the sulfurofluoridoimidate 6-6 itself was exposed to the aryl silyl ether ( 5-5 ) in the presence of DBU (10 mol%) over 16 h, SuFEx catalysis achieved linkage exchange at the fluorosulfate group, yielding the mixed sulfate-sulfurofluoridoimidate linked product 6-7 (Figure 7). From these few experiments, and related work, [7,15] we tentatively suggest the order of reactivity of SO 2 F 2 and SOF 4 derived S-F bonds towards SuFEx reactions with aryl silyl ethers: –N=SOF 2 > -SO 2 F > –OSO 2 F > –N=S(O)(OAr)F.…”

Section: Iminosulfur Oxydifluorides With Aryl Silyl Etherssupporting

confidence: 54%

“…Under SuFEx conditions the latent reactivity of the otherwise stable S VI –F bond is roused to react with SuFExable substrates. [7,15] …”

mentioning

confidence: 99%

“…[15] Of particular significance, however, is the potential for SuFEx in biochemical applications— we have growing evidence to believe that proteins provide molecular and dynamic electrostatic field environments that sulfur(VI) fluoride linkages are adept at reading and reacting to . [16] …”

mentioning

confidence: 99%

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Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF₄ Hub

et al. 2017

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Sulfur(VI) Fluoride Exchange (SuFEx) is a new family of click-chemistry based transformations that enables the synthesis of covalently linked modules via S(VI) hubs. Here we report on thionyl tetrafluoride (SOF4) as the first multidimensional SuFEx connector. SOF4 sits between the commercially mass-produced gases SF6 and SO2F2, and like them, is readily synthesized on scale. Under SuFEx catalysis conditions, SOF4 reliably seeks out 1º-amino groups [R-NH2] and becomes permanently anchored via a tetrahedral iminosulfur(VI)-link: R–N=(O=)S(F)2. The pendant, prochiral difluoride groups R–N=(O=)SF2, in turn, offer two further SuFExable handles, which can be sequentially exchanged to create 3-dimensional covalent departure vectors from the tetrahedral sulfur-(VI)-hub.

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Section: Iminosulfur Oxydifluorides With Aryl Silyl Etherssupporting

confidence: 54%

“…Under SuFEx conditions the latent reactivity of the otherwise stable S VI –F bond is roused to react with SuFExable substrates. [7,15] …”

mentioning

confidence: 99%

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Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF₄ Hub

et al. 2017

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“…We evaluated the effect of bases and co-solvents and found that, in the presence of 20 equivalents of Pd(OAc) 2 , 400 equivalents of boronic acid, and 1000 equivalents of triethylamine (Et 3 N) with N,N-dimethylaniline (DMA) as a co-solvent, the cross-coupling reaction proceeded smoothly with excellent conversion (90%) at room temperature in a ligand-free style (see Table S2, Supporting Information). [41,53] To further exploit the potential, it would be of great interest to perform stepwise chemo-selective on-DNA synthesis of polysubstituted aryl and/or heteroaryl molecules, [18] which are challenging tasks even in conventional organic synthesis. As shown in Scheme 1, the reaction displayed good reactivity and tolerance to aryl boronic acids with functional groups both electron-rich (KB1, KB2, KB3, KB4, KB16, KB19, and KB25) and electrondeficient (KB11, KB12, KB13, KB14, KB21, and KB24).…”

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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“…在 100 mL 的三颈烧瓶中加入 1.83 mmol 苯硼酸, 1.67 mmol 3-溴吡啶, 0.33 mmol NaHCO 3 作为碱, 0.002 g PdCl 2 作为催化剂, 溶剂为 30 mL 乙醇和水的混合溶液 [V(乙醇)∶V(水)＝2∶1], 在 90 ℃下反应 25 min [32] .…”

Section: Suzuki 反应unclassified

Surface Enhanced Raman Spectroscopy Coupled with High Performance Liquid Chromatography for Real-time Monitoring of Suzuki Coupling Reaction

Jiao¹,

Wang²,

Liu³

et al. 2018

Acta Chim. Sinica

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The surface enhanced Raman spectroscopy (SERS) has been employed in the structural characterization successfully due to its ultra-high sensitivity. However, it is still remained the significant difficulties in the precise interpretation of spectroscopy. Thus, it was not developed as the promising tool for monitoring the organic reaction directly. Herein, by using the two dimensional Au nanoparticles array film as substrate, the SERS was hyphenated with high performance liquid chromatography (HPLC). The individual advantages of high sensitivity of SERS and high efficiency in separation of HPLC were combined together, and it was extended successfully to real-time monitor of a Suzuki coupling reaction between 3-bromopyridine and phenylboronic acid. Firstly, the retention time and SERS spectra of standard solution of 3-bromopyridine and phenylboronic acid were performed respectively. It was beneficial for distinguishing the reactants of the current Suzuki reaction. After the reaction was proceeded for about 5 min, the mixture was sampled for the HPLC-SERS detection. It demonstrated that the chromatogram peaks located at 2.1 min and 2.8 min were contributed to phenylboronic acid and 3-bromopyridine, while 3.6 min and 15.3 min were originated from the reaction products. The solution collected at different retention times were then flowed through the catheter and dropped to the surface of Au nanoparticles arrays sequentially. The SERS spectra features were well agreement with that of 3-bromopyridine at 2.8 min, while the SERS spectra was absent for phenylboronic acid at 2.1 min due to its weak adsorption on Au surface. For the products, the typical vibrational modes of 3-phenylpyridine and diphenyl were observed in the SERS spectra, suggesting the composition of the product and byproduct. Meanwhile, the final product was confirmed by NMR spectroscopy, proving a structure of 3-phenylpyridine. Finally, the SERS results were well associated with the chromatographic peaks in a certain duration. It indicated that the HPLC-SERS technique would be a promising tool as a complementary approach to traditional techniques (such as LC-MS) for on line monitoring the organic reaction processes.

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Chemoselective Synthesis of Polysubstituted Pyridines from Heteroaryl Fluorosulfates

Cited by 77 publications

References 31 publications

Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF₄ Hub

Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF₄ Hub

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

Surface Enhanced Raman Spectroscopy Coupled with High Performance Liquid Chromatography for Real-time Monitoring of Suzuki Coupling Reaction

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Chemoselective Synthesis of Polysubstituted Pyridines from Heteroaryl Fluorosulfates

Cited by 77 publications

References 31 publications

Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF4 Hub

Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF4 Hub

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

Surface Enhanced Raman Spectroscopy Coupled with High Performance Liquid Chromatography for Real-time Monitoring of Suzuki Coupling Reaction

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Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF₄ Hub

Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF₄ Hub