- Late-Stage Amination of Drug-Like Benzoic Acids: Access to Anilines and Drug Conjugates through Directed Iridium-Catalyzed C?H Activation
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The functionalization of C?H bonds, ubiquitous in drugs and drug-like molecules, represents an important synthetic strategy with the potential to streamline the drug-discovery process. Late-stage aromatic C?N bond–forming reactions are highly desirable, but despite their significance, accessing aminated analogues through direct and selective amination of C?H bonds remains a challenging goal. The method presented herein enables the amination of a wide array of benzoic acids with high selectivity. The robustness of the system is manifested by the large number of functional groups tolerated, which allowed the amination of a diverse array of marketed drugs and drug-like molecules. Furthermore, the introduction of a synthetic handle enabled expeditious access to targeted drug-delivery conjugates, PROTACs, and probes for chemical biology. This rapid access to valuable analogues, combined with operational simplicity and applicability to high-throughput experimentation has the potential to aid and considerably accelerate drug discovery.
- Weis, Erik,Johansson, Magnus J.,Martín-Matute, Belén
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supporting information
p. 18188 - 18200
(2021/11/22)
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- One-pot synthesis of sulfonyl-1H-1,2,3-triazolyl-thiomorpholine 1,1-dioxide derivatives and evaluation of their biological activity
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A one-pot procedure for the synthesis of novel 1,2,3-triazole derivatives (5a–5l) in good yields (63 to 77%) using different sulfonic acids and 4-(prop-2-yn-1-yl)thiomorpholine 1,1-dioxide through the in situ generated sulfonyl azides was developed. The structures of the newly synthesized compounds were confirmed by 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. The newly synthesized compounds were screened for in?vitro antibacterial activity and free radical scavenging activity in terms of hydrogen donating or radical scavenging ability by the DPPH method. Among all, the compound N-(4-((4-((1,1-dioxidothiomorpholino) methyl)-1H-1,2,3-triazol-1-yl)sulfonyl)phenyl) acetamide (5l) was found to exhibit potent activity as compared to the standard drugs.
- Sreerama, Rakesh,Narasimha Swamy,Ravinder,Vasudeva Reddy,Narsimha, Sirassu
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p. 455 - 460
(2020/12/17)
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- Thermal Stability and Explosive Hazard Assessment of Diazo Compounds and Diazo Transfer Reagents
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Despite their wide use in academia as metal-carbene precursors, diazo compounds are often avoided in industry owing to concerns over their instability, exothermic decomposition, and potential explosive behavior. The stability of sulfonyl azides and other diazo transfer reagents is relatively well understood, but there is little reliable data available for diazo compounds. This work first collates available sensitivity and thermal analysis data for diazo transfer reagents and diazo compounds to act as an accessible reference resource. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and accelerating rate calorimetry (ARC) data for the model donor/acceptor diazo compound ethyl (phenyl)diazoacetate are presented. We also present a rigorous DSC dataset with 43 other diazo compounds, enabling direct comparison to other energetic materials to provide a clear reference work to the academic and industrial chemistry communities. Interestingly, there is a wide range of onset temperatures (Tonset) for this series of compounds, which varied between 75 and 160 °C. The thermal stability variation depends on the electronic effect of substituents and the amount of charge delocalization. A statistical model is demonstrated to predict the thermal stability of differently substituted phenyl diazoacetates. A maximum recommended process temperature (TD24) to avoid decomposition is estimated for selected diazo compounds. The average enthalpy of decomposition (?"HD) for diazo compounds without other energetic functional groups is-102 kJ mol-1. Several diazo transfer reagents are analyzed using the same DSC protocol and found to have higher thermal stability, which is in general agreement with the reported values. For sulfonyl azide reagents, an average ?"HD of-201 kJ mol-1 is observed. High-quality thermal data from ARC experiments shows the initiation of decomposition for ethyl (phenyl)diazoacetate to be 60 °C, compared to that of 100 °C for the common diazo transfer reagent p-acetamidobenzenesulfonyl azide (p-ABSA). The Yoshida correlation is applied to DSC data for each diazo compound to provide an indication of both their impact sensitivity (IS) and explosivity. As a neat substance, none of the diazo compounds tested are predicted to be explosive, but many (particularly donor/acceptor diazo compounds) are predicted to be impact-sensitive. It is therefore recommended that manipulation, agitation, and other processing of neat diazo compounds are conducted with due care to avoid impacts, particularly in large quantities. The full dataset is presented to inform chemists of the nature and magnitude of hazards when using diazo compounds and diazo transfer reagents. Given the demonstrated potential for rapid heat generation and gas evolution, adequate temperature control and cautious addition of reagents that begin a reaction are strongly recommended when conducting reactions with diazo compounds.
- Green, Sebastian P.,Wheelhouse, Katherine M.,Payne, Andrew D.,Hallett, Jason P.,Miller, Philip W.,Bull, James A.
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supporting information
p. 67 - 84
(2020/01/31)
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- Nitroacenaphthene as a New Photocatalyst for the Synthesis of Sulfonyl Amidines
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A small molecule, namely nitroacenaphthene, is reported for the first time as a recyclable visible-light photocatalyst for the construction of the C=N bond from sulfonyl azides and amines. This scalable, site-selective protocol provides a convenient way to access various sulfonyl amidines under mild conditions. Two reaction pathways are proposed, according to different transformation patterns.
- Chen, Ming,Jian, Yong,Xia, Wujiong,Yang, Chao
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p. 4425 - 4433
(2019/11/21)
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- Palladium-Catalyzed One-Pot Synthesis of N -Sulfonyl, N -Phosphoryl, and N -Acyl Guanidines
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An efficient palladium-catalyzed cascade reaction of azides with isonitrile and amines is presented; it offers an alternative facile approach toward N -sulfonyl-, N -phosphoryl-, and N -acyl-functionalized guanidines in excellent yield. These series of substituted guanidines exhibit potential biological and pharmacological activities. In addition, the less reactive intermediate benzoyl carbodiimide could be isolated by silica gel column flash chromatography in moderate yield.
- Qiao, Guanyu,Zhang, Zhen,Huang, Baoliang,Zhu, Liu,Xiao, Fan,Zhang, Zhenhua
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supporting information
p. 330 - 340
(2018/01/12)
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- A copper-catalyzed three component reaction of aryl acetylene, sulfonyl azide and enaminone to form iminolactone via 6π electrocyclization
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We developed a copper-catalyzed three component reaction of aryl acetylene, enaminone and sulfonyl azide to construct iminolactone via a cascade process involving copper-catalyzed alkyne-azide cycloaddition (CuAAC), Michael addition of metalated ketenimin
- Sun, Jiarui,Cheng, Xiangsheng,Mansaray, John Kamanda,Fei, Weihong,Wan, Jieping,Yao, Weijun
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supporting information
p. 13953 - 13956
(2019/01/03)
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- Synthesis of Sulfonyl Azides via Lewis Base Activation of Sulfonyl Fluorides and Trimethylsilyl Azide
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A protocol for the efficient conversion of sulfonyl fluorides into sulfonyl azides through Lewis base activation is described. The in situ generated sulfonyl azides are efficient diazo-transfer agents, affording diazo compounds and primary azides in excellent yields.
- Barrow, Andrew S.,Moses, John E.
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supporting information
p. 1840 - 1843
(2016/07/16)
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- Product-Derived Bimetallic Palladium Complex Catalyzes Direct Carbonylation of Sulfonylazides
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A novel product-derived bimetallic palladium complex catalyzes a sulfonylazide-transfer reaction with the σ-donor/π-acceptor ligand CO, and is advantageous given its broad substrate scope, high efficiency, and mild reaction conditions (atmospheric pressure of CO at room temperature). This methodology provides a new approach to sulfonylureas, which are present in both pharmaceuticals and agrochemicals. The synthesis of Glibenclamide on a gram scale further revealed the practical utility of this procedure. Mechanistically, the generation of a bridged bimetallic palladium species derived from the product sulfonylurea is disclosed as the crucial step for this catalytic cycle.
- Zhao, Jin,Li, Zongyang,Song, Shaole,Wang, Ming-An,Fu, Bin,Zhang, Zhenhua
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supporting information
p. 5545 - 5549
(2016/05/09)
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- Cu-catalyzed multicomponent polymerization to synthesize a library of poly(N -sulfonylamidines)
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We report a versatile Cu-catalyzed multicomponent polymerization (MCP) technique that enables the synthesis of high-molecular-weight, defect-free poly(N-sulfonylamidines) from monomers of diynes, sulfonyl azides, and diamines. Through a series of optimizations, we discovered that the addition of excess triethylamine and the use of N,N′-dimethylformamide as a solvent are key factors to ensure efficient MCP. Formation of cyclic polyamidines was a side reaction during polymerization, but it was readily controlled by using diynes or diamines with long or rigid moieties. In addition, this polymerization is highly selective for three-component reactions over click reactions. The combination of the above factors enables the synthesis of high-molecular-weight polymers, which was challenging in previous MCPs. All three kinds of monomers (diynes, sulfonyl azides, and diamines) are readily accessible and stable under the reaction conditions, with various monomers undergoing successful polymerization regardless of their steric and electronic properties. Thus, we synthesized various high-molecular-weight, defect-free polyamidines from a broad range of monomers while overcoming the limitations of previous MCPs, such as low conversion and defects in the polymer structures.
- Lee, In-Hwan,Kim, Hyunseok,Choi, Tae-Lim
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supporting information
p. 3760 - 3763
(2013/04/24)
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- Catalytic asymmetric synthesis of trisubstituted aziridines
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A method is described which provides for the direct asymmetric catalytic synthesis of trisubstituted aziridines from imines and diazo compounds. While unactivated imines were not reactive to α-diazo carbonyl compounds in which the diazo carbon was disubstituted, N-Boc imines react with both α-diazo esters and α-diazo-N-acyloxazolidinones to give trisubstituted aziridines with excellent diastereo- and enantioselectivities.
- Huang, Li,Wulff, William D.
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supporting information; experimental part
p. 8892 - 8895
(2011/08/04)
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- METAL PORPHYRIN CATALYZED OLEFIN AZIRIDINATION WITH SULFONYL AZIDES
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Cobalt(II) complex of P1 [Co(P1)], a new porphyrin that was designed on the basis of potential hydrogen bonding interactions in the metal-nitrene intermediate, is a highly active catalyst for olefin aziridination with azides. The [Co(P1)]- based system can be effectively employed for different combinations of aromatic olefins and arysulfonyl azides, synthesizing various sulfonylated aziridines in excellent yields. Besides its mild catalytic conditions, the Co-catalyzed aziridination process enjoys several attributes associated with the relatively low cost of cobalt and widely accessible arylsulfonyl azides. Furthermore, it generates stable dinitrogen as the only by-product.
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Page/Page column 36-37
(2009/12/27)
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- Convenient one-pot synthesis of sulfonyl azides from sulfonic acids
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We have developed a one-pot process for preparing sulfonyl azides by treating sulfonic acids with trichloroacetonitrile, triphenylphosphine, and sodium azide at room temperature. A wide range of sulfonyl azides was synthesized in excellent yields under mild conditions. Georg Thieme Verlag Stuttgart.
- Kim, Joong-Gon,Doo, Ok Jang
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experimental part
p. 2885 - 2887
(2009/04/21)
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- A highly effective cobalt catalyst for olefin aziridination with azides: Hydrogen bonding guided catalyst design
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[Co(P1)], which was designed on the basis of potential hydrogen-bonding interactions in the metal-nitrene Intermediate, Is a highly active aziridination catalyst with azides. [Co(P1)] can effectively azlridlnate various aromatic olefins with arylsulfonyl azides under mild conditions, forming sulfonylated aziridines in excellent yields. The Co-based system enjoys several attributes associated with the relatively low cost of cobalt and the wide accessibility of arylsulfonyl azides. Furthermore, it generates stable dinitrogen as the only byproduct.
- Ruppel, Joshua V.,Jones, Jess E.,Huff, Chelsea A.,Kamble, Rajesh M.,Chen, Ying,Zhang, X. Peter
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supporting information; experimental part
p. 1995 - 1998
(2009/04/10)
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- Deacylative oxidation strategy for the preparation of α- functionalized carbonyls
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(Matrix Presented) α-Alkoxylation and amination of carbonyl derivatives is made possible through a unique deacylative coupling reaction that proceeds via in situ Rh-carbene formation and subsequent heteroatom-H (X-H) insertion. Reactions perform optimally
- Brodsky, Benjamin H.,Du Bois
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p. 2619 - 2621
(2007/10/03)
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- CONVENIENT PREPARATION OF ARYL SULFONYL AZIDES UNDER TRIPHASE CATALYTIC CONDITIONS
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We wish to report an improved preparation method for the conversion of Aryl Sulfonyl Chlorides into Aryl Sulfonyl Azides, using polymer supported phase-transfer catalyst.
- Kumar, S. Madan
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p. 1015 - 1020
(2007/10/02)
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