- Visible Light-Mediated (Hetero)aryl Amination Using Ni(II) Salts and Photoredox Catalysis in Flow: A Synthesis of Tetracaine
-
We report a visible light-mediated flow process for C-N cross-coupling of (hetero)aryl halides with a variety of amine coupling partners through the use of a photoredox/nickel dual catalyst system. Compared to the method in batch, this flow process enables a broader substrate scope, including less-activated (hetero)aryl bromides and electron-deficient (hetero)aryl chlorides, and significantly reduced reaction times (10 to 100 min). Furthermore, scale up of the reaction, demonstrated through the synthesis of tetracaine, is easily achieved, delivering the C-N cross-coupled products in consistently high yield of 84% on up to a 10 mmol scale.
- Park, Boyoung Y.,Pirnot, Michael T.,Buchwald, Stephen L.
-
p. 3234 - 3244
(2020/02/04)
-
- Ru-Catalyzed Deoxygenative Transfer Hydrogenation of Amides to Amines with Formic Acid/Triethylamine
-
A ruthenium(II)-catalyzed deoxygenative transfer hydrogenation of amides to amines using HCO2H/NEt3 as the reducing agent is reported for the first time. The catalyst system consisting of [Ru(2-methylallyl)2(COD)], 1,1,1-tris(diphenylphosphinomethyl) ethane (triphos) and Bis(trifluoromethane sulfonimide) (HNTf2) performed well for deoxygenative reduction of various secondary and tertiary amides into the corresponding amines in high yields with excellent selectivities, and exhibits high tolerance toward functional groups including those that are reduction-sensitive. The choice of hydrogen source and acid co-catalyst is critical for catalysis. Mechanistic studies suggest that the reductive amination of the in situ generated alcohol and amine via borrowing hydrogen is the dominant pathway. (Figure presented.).
- Pan, Yixiao,Luo, Zhenli,Xu, Xin,Zhao, Haoqiang,Han, Jiahong,Xu, Lijin,Fan, Qinghua,Xiao, Jianliang
-
supporting information
p. 3800 - 3806
(2019/07/12)
-
- B(C6F5)3-Catalyzed Deoxygenative Reduction of Amides to Amines with Ammonia Borane
-
The first B(C6F5)3-catalyzed deoxygenative reduction of amides into the corresponding amines with readily accessible and stable ammonia borane (AB) as a reducing agent under mild reaction conditions is reported. This metal-free protocol provides facile access to a wide range of structurally diverse amine products in good to excellent yields, and various functional groups including those that are reduction-sensitive were well tolerated. This new method is also applicable to chiral amide substrates without erosion of the enantiomeric purity. The role of BF3 ? OEt2 co-catalyst in this reaction is to activate the amide carbonyl group via the in situ formation of an amide-boron adduct. (Figure presented.).
- Pan, Yixiao,Luo, Zhenli,Han, Jiahong,Xu, Xin,Chen, Changjun,Zhao, Haoqiang,Xu, Lijin,Fan, Qinghua,Xiao, Jianliang
-
supporting information
p. 2301 - 2308
(2019/01/30)
-
- Synthesis and Pharmacological Evaluation of Selective Histone Deacetylase 6 Inhibitors in Melanoma Models
-
Only a handful of therapies offer significant improvement in the overall survival in cases of melanoma, a cancer whose incidence has continued to rise in the past 30 years. In our effort to identify potent and isoform-selective histone deacetylase (HDAC) inhibitors as a therapeutic approach to melanoma, a series of new HDAC6 inhibitors based on the nexturastat A scaffold were prepared. The new analogues 4d, 4e, and 7b bearing added hydrophilic substituents, so as to establish additional hydrogen bonding on the rim of the HDAC6 catalytic pocket, exhibit improved potency against HDAC6 and retain selectivity over HDAC1. Compound 4d exhibits antiproliferative effects on several types of melanoma and lymphoma cells. Further studies indicates that 4d selectively increases acetylated tubulin levels in vitro and elicits an immune response through down-regulating cytokine IL-10. A preliminary in vivo efficacy study indicates that 4d possesses improved capability to inhibit melanoma tumor growth and that this effect is based on the regulation of inflammatory and immune responses.
- Tavares, Maurício T.,Shen, Sida,Knox, Tessa,Hadley, Melissa,Kutil, Zsófia,Ba?inka, Cyril,Villagra, Alejandro,Kozikowski, Alan P.
-
supporting information
p. 1031 - 1036
(2017/10/18)
-
- Room-Temperature Practical Copper-Catalyzed Amination of Aryl Iodides
-
An efficient and highly practical procedure is reported for the Ullmann-Goldberg-type copper-catalyzed amination of aryl iodides. By using a combination of copper iodide and proline in the presence of an excess of an amine, a wide range of aryl iodides can be readily aminated at room temperature. The reaction proceeds well regardless of the electronic properties of the starting aryl iodide and the amination products can be obtained without the need for purification by column chromatography in most cases. Owing to its efficiency and the mildness of the reaction conditions, this amination could also be extended to the amination of complex aryl iodides at room temperature.
- Deldaele, Christopher,Evano, Gwilherm
-
p. 1319 - 1328
(2016/04/20)
-
- Structure-activity relationship study of non-steroidal NPC1L1 ligands identified through cell-based assay using pharmacological chaperone effect as a readout
-
Niemann-Pick type C1-like 1 (NPC1L1) is an intestinal cholesterol transporter that is known to be the target of the cholesterol absorption inhibitor ezetimibe. We previously discovered steroidal NPC1L1 ligands by using a novel cell-based assay that employs pharmacological chaperone effect as a readout. Those steroid derivatives bound to a site different from both the sterol-binding domain and the ezetimibe-binding site, implying that they may be a novel class of NPC1L1 inhibitors with a distinct mode of action. As an extension of that work, we aimed here to find non-steroidal NPC1L1 ligands, which may be better candidates for clinical application than steroidal ligands, by using the same assay to screen our focused library of ligands for liver X receptor (LXR), a nuclear receptor that recognizes oxysterols as endogenous ligands. Here we describe identification of a novel class of NPC1L1 ligands with a ring-fused quinolinone scaffold, and an analysis of the structure-activity relationships of their derivatives as NPC1L1 ligands.
- Karaki, Fumika,Ohgane, Kenji,Fukuda, Hiromitsu,Nakamura, Masahiko,Dodo, Kosuke,Hashimoto, Yuichi
-
p. 3587 - 3609
(2014/07/07)
-
- Use of primary amines for the selective n-alkylation of anilines by a reusable heterogeneous catalyst
-
Traditionally, anilines can be alkylated with reactive alkyl halides but now more safe reagents such as alcohols or even amines can be used. To overcome the limits of homogeneous catalysis for aniline N-alkylation, we have developed a protocol that employs simple Pd/C as a heterogeneous catalyst under microwave dielectric heating. The process, based on the easy Pd-mediated oxidation of primary amines to imines followed by aniline addition, is characterized by a high atom economy as ammonia is the only other product of the reaction. This kind of aniline alkylation with amines has been carried out both in ionic liquid medium using [bmim]PF6 or in a more traditional solvent such as THF where the catalyst could be successfully recycled more times. The reusability of the catalyst was further confirmed by using material recycled from the amination in a standard alkene hydrogenation without loss of efficiency. Georg Thieme Verlag Stuttgart New York.
- Linciano, Pasquale,Pizzetti, Marianna,Porcheddu, Andrea,Taddei, Maurizio
-
p. 2249 - 2254
(2013/11/06)
-
- SUBSTITUTED SULFONAMIDES USEFUL AS ANTIAPOPTOTIC BCL INHIBITORS
-
Disclosed are compounds of Formula (I), or a pharmaceutically acceptable salt thereof, wherein: W and Q and G are defined herein. Also disclosed are methods of using such compounds as inhibitors of Bcl-2 family antiapoptotic proteins for the treatment of cancer; and pharmaceutical compositions comprising such compounds.
- -
-
Page/Page column 222
(2012/12/13)
-
- Reactions of arenediazonium o-benzenedisulfonimides with aliphatic triorganoindium compounds
-
The reaction of various arenediazonium o-benzenedisulfonimides with aliphatic triorganoindium compounds is described. Surprisingly, with triethyl- or tributylindium we obtained N-ethyl- or N-butylanilines, respectively. This is the first case in which, at least formally, the reactive site of a diazonium salt is the nitrogen atom directly bonded to the aromatic ring. In contrast, with trimethylindium we obtained only formaldehyde (aryl)hydrazones. In order to explain the difference between trimethyl- and triethylindium we have proposed some reaction mechanisms, supported by detailed density functional (DFT) calculations. The possible role of diazene/hydrazone tautomerism initially assumed was discarded and therefore three mechanisms for the key step (nucleophilic addition of the trialkylindium to the N=N double bond of diazene) were studied. For the favoured mechanism there is a difference in the energy barriers of 2 kcalmol-1 between the reactions with trimethyl- and triethylindium. This difference is explained on the basis of the different C-In bond energies in the two organometallics and it is assumed to be enough to explain their different behaviour under the experimental conditions. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Barbero, Margherita,Cadamuro, Silvano,Dughera, Stefano,Ghigo, Giovanni
-
scheme or table
p. 862 - 868
(2009/04/11)
-
- A new class of nifuroxazide analogues: Synthesis of 5-nitrothiophene derivatives with antimicrobial activity against multidrug-resistant Staphylococcus aureus
-
Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been an increasing problem worldwide since the initial reports over 40 years ago. To examine new drug leads with potential antibacterial activities, 14 p-substituted benzoic acid [(5-nitro-thiophen-2-yl)-methylene]-hydrazides were designed, synthesized, and tested against standard and multidrug-resistant S. aureus strains by serial dilution tests. All compounds exhibited significant bacteriostatic activity and some of them also showed bactericidal activity. The results confirmed the potential of this class of compounds as an alternative for the development of selective antimicrobial agents.
- Masunari, Andrea,Tavares, Leoberto Costa
-
p. 4229 - 4236
(2008/03/13)
-
- Synthesis of bulky and electron-rich MOP-type ligands and their applications in palladium-catalyzed C-N bond formation
-
A series of 2-dialkylphosphino-2′-alkoxy-1,1′-binaphthyl ligands (6a-c and 8a-c) have been prepared conveniently by a lithium-initiated ring-opening reaction of dinaphthofuran, followed by selective phosphorylation. These compounds displayed a remarkable air and moisture stability, both in solid form and in solution. Application of these phosphine ligands in palladium-catalyzed C-N bond forming reactions revealed the crucial roles of the steric bulk of the substituents on the phosphorus atom governing the catalytic activity. Specifically, 2-di-tert-butylphosphino-2′-isopropoxy-1,1′- binaphthyl (8b) proved to be the most effective for the aminations of aryl halides with primary amines, while the less bulky 2-dicyclohexyl-2′- methoxy-1,1′-binaphthyl (6a) was more effective for the aminations with secondary amines. The steric and electronic effects of the ligands were analyzed to account for these observations.
- Xie, Xiaomin,Zhang, Tony Y.,Zhang, Zhaoguo
-
p. 6522 - 6529
(2007/10/03)
-
- A general procedure to selectively prepare N-alkylanilines by an unexpected reaction of (Z)-(tert-butylsulfanyl)(aryl)diazenes with alkyllithium reagents
-
A general procedure has been set up to prepare, selectively, the N-monoalkylanilines 7, reacting (Z)-(tert-butylsulfanyl)(aryl)diazenes 3 with alkyllithium 6 (MeLi, BuLi, s-BuLi, n-C6H13Li). The reactions were carried out in anhydrous diethyl ether at 0°C or - 78°C, depending on the reagent 6, and then at room temperature. In optimal conditions the yields of the pure products 7 (uncontaminated by dialkylation products) were from good to excellent: for 38 considered examples, 34 were positive with yields varying between 61percent and 91percent (average yield 78percent). Collateral proofs were carried out to support a hypothesized reaction mechanism.
- Barbero, Margherita,Degani, Iacopo,Dughera, Stefano,Fochi, Rita
-
p. 742 - 750
(2007/10/03)
-