- Hypervalent Iodonium Alkynyl Triflate Generated Phenylcyanocarbene and Its Reactivity with Aromatic Systems
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Phenylcyanocarbene was generated by the reaction of azide with a hypervalent iodonium alkynyl triflate and reacted in situ with 21 different carbocyclic and heterocyclic aromatic compounds. These reactions led to more complex products that frequently underwent subsequent rearrangements. The reactivity was further explored in a mechanistic study to ascertain the chemoselectivity and stereospecificity.
- Al-Huniti, Mohammed H.,Sullivan, Zachary B.,Stanley, Jarrod L.,Carson, James A.,Hyatt, I. F. Dempsey,Hairston, A. Christina,Croatt, Mitchell P.
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- Structure-Based Design of High-Affinity Fluorescent Probes for the Neuropeptide Y Y1Receptor
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The recent crystallization of the neuropeptide Y Y1 receptor (Y1R) in complex with the argininamide-type Y1R selective antagonist UR-MK299 (2) opened up a new approach toward structure-based design of nonpeptidic Y1R ligands. We designed novel fluorescent probes showing excellent Y1R selectivity and, in contrast to previously described fluorescent Y1R ligands, considerably higher (~100-fold) binding affinity. This was achieved through the attachment of different fluorescent dyes to the diphenylacetyl moiety in 2 via an amine-functionalized linker. The fluorescent ligands exhibited picomolar Y1R binding affinities (pKi values of 9.36-9.95) and proved to be Y1R antagonists, as validated in a Fura-2 calcium assay. The versatile applicability of the probes as tool compounds was demonstrated by flow cytometry- and fluorescence anisotropy-based Y1R binding studies (saturation and competition binding and association and dissociation kinetics) as well as by widefield and total internal reflection fluorescence (TIRF) microscopy of live tumor cells, revealing that fluorescence was mainly localized at the plasma membrane.
- Müller, Christoph,Gleixner, Jakob,Tahk, Maris-Johanna,Kopanchuk, Sergei,Laasfeld, T?nis,Weinhart, Michael,Schollmeyer, Dieter,Betschart, Martin U.,Lüdeke, Steffen,Koch, Pierre,Rinken, Ago,Keller, Max
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p. 4832 - 4853
(2022/03/27)
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- Palladium-Catalyzed Direct α-Arylation of Arylacetonitriles with Aryl Tosylates and Mesylates
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The first general palladium-catalyzed α-arylation of arylacetonitriles with aryl and heteroaryl sulfonates are reported. Pd(OAc)2 associated with XPhos serves as the effective catalyst to facilitate this reaction. A broad range of electron-rich, -neutral, -deficient, and sterically hindered aryl/heteroaryl tosylates and mesylates are coupled with arylacetonitriles bearing different substituents to give the corresponding products in good to excellent yields. Catalyst loading down to 0.1 mol-% Pd was achieved, and 22 unprecedented compounds were synthesized from 43 demonstrated examples using this method. Its applicability with the modification of biological phenolic compounds was successfully demonstrated. The Pd/XPhos system catalyzed the α-arylation and followed by alkylation in one-pot sequential conditions, resulting in the direct synthesis of compounds containing quaternary center- and deuterium-containing compounds in good to excellent yields.
- Yuen, On Ying,Chen, Xiangmeng,Wu, Junyu,So, Chau Ming
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supporting information
p. 1912 - 1916
(2020/03/13)
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- Scalable α-Arylation of Nitriles in Aqueous Micelles using Ultrasmall Pd Nanoparticles: Surprising Formation of Carbanions in Water
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A scalable synthetic method is described for both the preparation of ultrasmall palladium nanoparticles and their subsequent use in catalyzing an α-arylation reaction of nitriles in aqueous micelles. This method involves the intermediacy of carbanions or keteniminates, which are presumably stabilized by the micellar environment rather than being quenched with water. These Pd nanoparticles are thoroughly characterized. Mechanistic studies using 31P NMR spectroscopy revealed the binding of phosphine ligand with the Pd surface and control experiment confirmed the zero-oxidation state of palladium. The scope of the transformation is demonstrated over 35 examples, including one at 50 g scale.
- Ansari, Tharique N.,Bihani, Manisha,Bora, Pranjal P.,Finck, Lucie,Handa, Sachin,Jasinski, Jacek B.,Leahy, David K.,Pavuluri, Bhavana
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p. 6816 - 6821
(2020/07/16)
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- Synthesis of Chiral Triarylmethanes Bearing All-Carbon Quaternary Stereocenters: Catalytic Asymmetric Oxidative Cross-Coupling of 2,2-Diarylacetonitriles and (Hetero)arenes
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A direct and enantioselective oxidative cross-coupling of racemic 2,2-diarylacetonitriles with electron-rich (hetero)arenes has been described, which allows for efficient construction of triarylmethanes bearing all-carbon quaternary stereocenters with excellent chemo- and enantioselectivity. The reaction has an excellent functional group tolerance, and exhibits a broad scope with respect to both 2,2-diarylacetonitrile and (hetero)arene components. The rich chemistry of the cyano group allows for facile synthesis of other valuable chiral triarylmethanes bearing all-carbon quaternary centers that are otherwise difficult to access.
- Wang, Zehua,Zhu, Yasheng,Pan, Xiaoguang,Wang, Gang,Liu, Lei
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supporting information
p. 3053 - 3057
(2020/02/05)
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- 2-ETHYLIDENE-1,5-DIMETHYL-3,3-DIPHENYLPYRROLIDINE ANALOGS AND METHODS FOR THEIR SYNTHESIS AND USE
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The present invention relates to novel 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine analogs, and methods for their synthesis and use. Such analogs are designed to provide a convenient linkage chemistry for coupling under mild conditions to a suitable group on a target protein, polypeptide, solid phase or detectable label.
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Paragraph 00154
(2017/12/15)
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- BF3·OEt2-mediated [1,2]-aryl shift: Synthesis of functionalized α-arylnitriles via the bromination/cyanation/deformylation of substituted deoxybenzoin
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A new sequential, tandem synthesis of functionalized α-arylnitriles via the bromination/cyanation/deformylation of substituted deoxybenzoin has developed. CuBr2-promoted bromination of substituted deoxybenzoins gives 2-bromo-2-arylacetophenne 3. The cyanation of 3 with sodium cyanide (NaCN) generates epoxynitrile. Then, a treatment of epoxynitrile with BF3·OEt2 results in the formation of functionalized α-arylnitriles 4 via a 1,2-aryl shift.
- Chan, Chieh-Kai,Chang, Meng-Yang
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p. 5207 - 5213
(2017/07/28)
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- Palladium-Catalyzed Regiodivergent Substitution of Propargylic Carbonates
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The palladium(0)-catalyzed, ligand-controlled, regioselective addition of diaryl acetonitrile pronucleophiles to propargylic carbonates is reported. Selective formation of either terminal 1,3-dienyl or propargylated products is proposed to arise from a change in reaction mechanism controlled by the denticity of the coordinating ligand.
- Locascio, Theresa M.,Tunge, Jon A.
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p. 18140 - 18146
(2016/12/16)
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- Nitroalkenes as surrogates for cyanomethylium species in a one-pot synthesis of non-symmetric diarylacetonitriles
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Nitroalkenes were used as synthetic equivalents of the cyanomethylium cation in a modular, one-pot synthesis of 2-(3-indolyl)acetonitriles and 2,2-diarylacetonitriles involving electrophilic functionalization of aromatic and heteroaromatic C-H bond.
- Aksenov, Alexander V.,Aksenov, Nicolai A.,Dzhandigova, Zarema V.,Aksenov, Dmitrii A.,Rubin, Michael
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p. 106492 - 106497
(2016/01/15)
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- The Concise Synthesis of Unsymmetric Triarylacetonitriles via Pd-Catalyzed Sequential Arylation: A New Synthetic Approach to Tri- and Tetraarylmethanes
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The selective synthesis of multiarylated acetonitriles via sequential palladium-catalyzed arylations of chloroacetonitrile is reported. The three aryl groups are installed via a Pd-catalyzed Suzuki-Miyaura cross coupling reaction followed by back-to-back C-H arylations to afford triarylacetonitriles in three steps with no over-arylation at any step. The triarylacetonitrile products can be converted into highly functionalized species including tetraarylmethanes. This new strategy provides rapid access to a variety of unsymmetrical tri- and tetraarylmethane derivatives from simple, readily available starting materials. (Chemical Presented)
- Nambo, Masakazu,Yar, Muhammad,Smith, Joel D.,Crudden, Cathleen M.
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- Efficient assembly of α-aryl and α-vinyl nitriles via iron-catalyzed ether bond activation
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A novel and practical method for the synthesis of diverse α-aryl and α-vinyl nitriles was developed via an iron-catalyzed sp3 C-O ether bond cleavage with C-C bond formation in the reaction of π-activated ethers with TMSCN.
- Fan, Xiaohui,Guo, Kun,Guan, Yong-Hong,Fu, Lin-An,Cui, Xiao-Meng,Lv, Hao,Zhu, Hong-Bo
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supporting information
p. 1068 - 1071
(2014/02/14)
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- Efficient assembly of α-aryl and α-vinyl nitriles via iron-catalyzed ether bond activation
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A novel and practical method for the synthesis of diverse α-aryl and α-vinyl nitriles was developed via an iron-catalyzed sp3 C-O ether bond cleavage with C-C bond formation in the reaction of π-activated ethers with TMSCN.
- Fan, Xiaohui,Guo, Kun,Guan, Yong-Hong,Fu, Lin-An,Cui, Xiao-Meng,Lv, Hao,Zhu, Hong-Bo
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supporting information
p. 1068 - 1071
(2015/02/18)
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- Zn(OTf)2 - Catalyzed direct cyanation of benzylic alcohols - A novel synthesis of α-aryl nitriles
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This work demonstrates an efficient method to prepare α-aryl nitriles by direct cyanation of benzylic alcohol with TMSCN in the presence of a catalytic amount of Zn(OTf)2 under heating condition. A variety of benzylic alcohols can be converted into the corresponding α-aryl nitriles in good to excellent yields. 2012 Elsevier Ltd. All rights reserved.
- Theerthagiri, Palani,Lalitha, Appaswami
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supporting information
p. 5535 - 5538
(2012/11/07)
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- Synthesis and structure-activity relationships of A novel class of dithiocarbamic acid esters as anticancer agent
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Based on a novel lead compound 4-methylpiperazine-1-carbodithioic acid 3-cyano-3,3-diphenylpropyl ester 1, the systematic structural modification was carried out. All the synthesized compounds were evaluated for their in-vitro anticancer activities on four to six different cell lines at three different concentrations. Most of the tested compounds could selectively inhibit the growth of HL-60 and Bel-7402 cell lines at a medium concentration. Four compounds (3f, 3g, 3n, and 5) were selected for the IC50 test, and the results revealed that three compounds (3g, 3n, and 5) showed almost the same or a slightly weaker activity than compound 1 against HL-60, and three compounds (3f, 3g, and 3n) showed >2-fold higher potency than compound 1 against Bel-7402. The in-vivo efficacy of 3n · HCl was evaluated with transplanted hepatocyte carcinoma 22 as an in-vivo test model. It was found that 3n · HCl could inhibit significantly the growth of tumor, and that this effect was dose-dependent. Meanwhile, the compound 3n · HCl showed low toxicity compared with compound 1 · HCl as evidenced by the little body-weight loss. These results confirmed that compound 3n · HCl is more potent than the lead compound 1 · HCl. Preliminary structure-activity relationships indicated that: a) Both nitrile group and the cyclic amine containing at least two nitrogens were indispensable moieties to keep the activity; b) substitution of the piperazine ring is unfavorable for the improvement of activity; c) the suitable linker joining the piperazinyl dithiocarboxyl and diphenylacetonitril group should be ethylene; d) a non-coplanar arrangement of the two benzene rings appears to be essential for activity. Based on a novel lead compound 4-methyl-piperazine-1-carbodithioic acid 3-cyano-3,3-diphenyl-propyl ester 1, the systematic structural modification was carried out. Compounds 3g and 3n were found to show more potent biological activities than lead compound 1. Some useful SARs were revealed Copyright
- Hou, Xueling,Ge, Zemei,Wang, Tingmin,Guo, Wei,Wu, Jun,Cui, Jingrong,Lai, Chingsan,Li, Runtao
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scheme or table
p. 320 - 332
(2011/11/05)
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- Facile preparation of α-aryl nitriles by direct cyanation of alcohols with TMSCN under the catalysis of InX3
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(Chemical Equation Presented) A convenient and efficient synthesis of α-aryl nitrites was developed by direct cyanation of alcohols with TMSCN under the catalysis of Lewis acid. Using 5-10 mol % of InBr3 as the catalyst, a variety of benzylic alcohols can be converted to the corresponding nitriles in 5-30 min with yields of 46-99%.
- Chen, Gang,Wang, Zheng,Wu, Jiang,Ding, Kuiling
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supporting information; experimental part
p. 4573 - 4576
(2009/05/07)
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- Phenyl-substituted normethadones: Synthesis and pharmacology
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Phenyl-substituted normethadone derivatives were synthesized and their affinity (IC50) for opioid receptors was determined by displacement of the specific binding sites of [3H]sufentanyl on rat brain preparations. Substitution resulted in a decrease of affinity in-vitro. These results suggest that normethadone-like compounds may interact with the P subsite of the μ-opioid receptor and that the P subsite has a well-defined cavity shape of stringent dimensions.
- Mbela,Poupaert,Cumps,Moussebois,Haemers,Borloo,Dumont
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p. 237 - 242
(2007/10/02)
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- p-Hydroxymethadone: Synthesis, Crystal Structure and CD Properties
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Alkylation of 2-chloro-N,N-dimethylpropylamine 2 with the lithium salt derived from 2-(p-methoxyphenyl)-2-phenylacetonitrile 1 afforded a mixture of p-methoxymethadone nitrile 3 and p-methoxyisomethadone nitrile 4.The nitriles were separated chromatographically and the amino nitrile 3 was converted subsequently into the diastereoisomeric p-hydroxymethadone 8 hydrochlorides.Careful recrystallization afforded a separation of the (4RS,6RS)- and (4RS,6SR)-p-hydroxymethadone hydrochlorides.Repetition of the synthesis using (R)-2-chloro-N,N-dimethylpropylamine, derived in three steps from (S)-dilactide 9, yielded the (4S,6S)- and (4R,6S)-p-hydroxymethadone hydrochlorides, which were also separated by fractional crystallization.The absolute configuration of the products was verified by X-ray crystallography.The (4R,6S) salt exhibited a more intense Cotton effect than (S)-methadone hydrochloride while the (4S,6S) salt showed a less intense Cotton effect and less fine structure in the λ 260-275 nm range.
- Brine, George A.,Boldt, Karl G.,Prakash, Doriswamy,Kotchmar, Dennis J.,Bondeson, Virginia C.,et al.
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p. 1809 - 1814
(2007/10/02)
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- Benzylic Cyanation via Oxidation and Simultaneous Nucleophilic Substitution
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Use of dichlorodicyano benzoquinone and trimethylsilyl cyanide in suitable solvent permits the direct and ready transformation of benzylic C-H bonds to C-CN bonds with high yield and selectivity via oxidation and simultaneous nucleophilic substitution.
- Lemaire, Marc,Doussot, Joel,Guy, Alain
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p. 1581 - 1584
(2007/10/02)
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