3027-13-2Relevant academic research and scientific papers
Catalytic SNAr Hydroxylation and Alkoxylation of Aryl Fluorides
Kang, Qi-Kai,Li, Ke,Li, Yuntong,Lin, Yunzhi,Shi, Hang,Xu, Lun
supporting information, p. 20391 - 20399 (2021/08/13)
Nucleophilic aromatic substitution (SNAr) is a powerful strategy for incorporating a heteroatom into an aromatic ring by displacement of a leaving group with a nucleophile, but this method is limited to electron-deficient arenes. We have now established a reliable method for accessing phenols and phenyl alkyl ethers via catalytic SNAr reactions. The method is applicable to a broad array of electron-rich and neutral aryl fluorides, which are inert under classical SNAr conditions. Although the mechanism of SNAr reactions involving metal arene complexes is hypothesized to involve a stepwise pathway (addition followed by elimination), experimental data that support this hypothesis is still under exploration. Mechanistic studies and DFT calculations suggest either a stepwise or stepwise-like energy profile. Notably, we isolated a rhodium η5-cyclohexadienyl complex intermediate with an sp3-hybridized carbon bearing both a nucleophile and a leaving group.
N-Phenyl-1,2,3,4-tetrahydroisoquinoline: An Alternative Scaffold for the Design of 17β-Hydroxysteroid Dehydrogenase 1 Inhibitors
Mottinelli, Marco,Sinreih, Ma?a,Ri?ner, Tea L.,Leese, Mathew P.,Potter, Barry V. L.
, p. 259 - 291 (2020/12/07)
17β-Hydroxysteroid dehydrogenases catalyse interconversion at the C17 position between oxidized and reduced forms of steroidal nuclear receptor ligands. The type 1 enzyme, expressed in malignant cells, catalyses reduction of the less-active estrone to estradiol, and inhibitors have therapeutic potential in estrogen-dependent diseases such as breast and ovarian cancers and in endometriosis. Synthetic decoration of the nonsteroidal N-phenyl-1,2,3,4-tetrahydroisoquinoline (THIQ) template was pursued by using Pomeranz-Fritsch-Bobbitt, Pictet-Spengler and Bischler-Napieralski approaches to explore the viability of this scaffold as a steroid mimic. Derivatives were evaluated biologically in vitro as type 1 enzyme inhibitors in a bacterial cell homogenate as source of recombinant protein. Structure-activity relationships are discussed. THIQs possessing a 6-hydroxy group, lipophilic substitutions at the 1- or 4-positions in combination with N-4′-chlorophenyl substitution were most favourable for activity. Of these, one compound had an IC50 of ca. 350 nM as a racemate, testifying to the applicability of this novel approach.
Synthesis of Benzo[ b]furans by Intramolecular C-O Bond Formation Using Iron and Copper Catalysis
Henry, Martyn C.,Sutherland, Andrew
supporting information, p. 2766 - 2770 (2020/03/30)
One-pot processes for the synthesis of benzo[b]furans from 1-aryl- or 1-alkylketones using nonprecious transition metal catalysts have been developed. Regioselective iron(III)-catalyzed halogenation of the aryl ring, followed by iron- or copper-catalyzed O-arylation allowed the synthesis of various structural analogues, including the benzo[b]furan-derived natural products corsifuran C, moracin F, and caleprunin B.
An Efficient Palladium-Catalyzed α-Arylation of Acetone below its Boiling Point
Ledgard, Andrew J.,Martin, Fionna M.,Mutton, Simon P.,Richardson, Jeffery,Walton, Lesley
, (2020/07/24)
The monoarylation of acetone is a powerful transformation, but is typically performed at temperatures significantly in excess of its boiling point. Conditions described for performing the reaction at ambient temperatures led to significant dehalogenation when applied to a complex aryl halide. We describe our attempts to overcome both issues in the context of our drug-discovery program.
Nickel-Catalyzed Mono-Selective α-Arylation of Acetone with Aryl Chlorides and Phenol Derivatives
Amgoune, Abderrahmane,Derhamine, Sary Abou,Krachko, Tetiana,Monteiro, Nuno,Pilet, Guillaume,Schranck, Johannes,Tlili, Anis
supporting information, p. 18948 - 18953 (2020/09/01)
The challenging nickel-catalyzed mono-α-arylation of acetone with aryl chlorides, pivalates, and carbamates has been achieved for the first time. A nickel/Josiphos-based catalytic system is shown to feature unique catalytic behavior, allowing the highly selective formation of the desired mono-α-arylated acetone. The developed methodology was applied to a variety of (hetero)aryl chlorides including biologically relevant derivatives. The methodology has been extended to the unprecedented coupling of acetone with phenol derivatives. Mechanistic studies allowed the isolation and characterization of key Ni0 and NiII catalytic intermediates. The Josiphos ligand is shown to play a key role in the stabilization of NiII intermediates to allow a Ni0/NiII catalytic pathway. Mechanistic understanding was then leveraged to improve the protocol using an air-stable NiII pre-catalyst.
Expeditious Synthesis of Isoquinolone Derivatives by Rhodium(I)-Catalyzed Annulation Reaction through C-C Bond Cleavage
He, Yiyi,Yuan, Chengsha,Jiang, Zeqi,Shuai, Li,Xiao, Qing
supporting information, p. 185 - 189 (2019/01/04)
A Rh(I)-catalyzed intermolecular cyclization between isocyanates and benzocyclobutenols leading to isoquinolin-1(2H)-ones through selective cleavage of a C-C bond has been realized. Exploiting the same strategy, we developed a Rh(I)-catalyzed three-component reaction of benzocyclobutenols, isonitriles, and sulfonyl azides to access isoquinolin-1(2H)-imines. These procedures provide unique and expeditious access to isoquinolone derivatives which are otherwise difficult to prepare in satisfactory yields with excellent functional-group tolerance under mild reaction conditions.
Porphyrins as Photoredox Catalysts in Csp2-H Arylations: Batch and Continuous Flow Approaches
De Souza, Aline A. N.,Silva, Nathalia S.,Müller, Andressa V.,Polo, André S.,Brocksom, Timothy J.,De Oliveira, Kleber T.
, p. 15077 - 15086 (2019/01/03)
We have investigated both batch and continuous flow photoarylations of enol-acetates to yield different α-arylated aldehyde and ketone building blocks by using diazonium salts as the aryl-radical source. Different porphyrins were used as SET photocatalysts, and photophysical as well as electrochemical studies were performed to rationalize the photoredox properties and suggest mechanistic insights. Notably, the most electron-deficient porphyrin (meso-tetra(pentafluorophenyl)porphyrin) shows the best photoactivity as an electron donor in the triplet excited state, which was rationalized by the redox potentials of excited states and the turnover of the porphyrins in the photocatalytic cycle. A two-step continuous protocol and multigram-scale reactions are also presented revealing a robust, cost-competitive, and easy methodology, highlighting the significant potential of porphyrins as SET photocatalysts.
Synthesis of Functionalized Dihydrobenzofurans by Direct Aryl C?O Bond Formation under Mild Conditions
Alvarado, Joseph,Fournier, Jeremy,Zakarian, Armen
supporting information, p. 11625 - 11628 (2016/10/24)
A method for the synthesis of dihydrobenzofurans by a direct aryl C?O bond formation is described. A mechanistic pathway for the reaction, distinct from previously described similar transformations, allows for mild reaction conditions that are expected to be compatible with functionalized substrates.
Direct Asymmetric Reductive Amination for the Synthesis of Chiral β-Arylamines
Huang, Haizhou,Liu, Xiaoyan,Zhou, Le,Chang, Mingxin,Zhang, Xumu
supporting information, p. 5309 - 5312 (2016/04/26)
The highly efficient and direct asymmetric reductive amination of arylacetones catalyzed by an iridium complex for the preparation of enantiomerically pure β-arylamines is described. The monodentate phosphoramidite ligand exhibits superb reactivity (TONs of up to 20 000) and enantioselectivity (up to 99 % ee). Additives played important roles in this reductive coupling reaction. Asymmetric reductive coupling of a ketone and an amine is a straightforward and atom-economic approach for preparing optically enriched amines. The highly efficient and direct asymmetric reductive amination of arylacetones, catalyzed by an iridium complex, supplies enantiomerically pure β-arylamines. The new phosphoramidite ligands reported show superb reactivity and enantioselectivity in this reductive coupling. M.S.=molecular sieves, TFA=trifluoroacetic acid.
Palladium-Catalyzed Mono-α-arylation of Acetone at Room Temperature
Macqueen, Preston M.,Chisholm, Alicia J.,Hargreaves, Breanna K. V.,Stradiotto, Mark
supporting information, p. 11006 - 11009 (2015/11/10)
The first examples of acetone mono-α-arylation at room temperature are described, enabled by use of a [Pd(cinnamyl)Cl]2/JosiPhos catalyst system. (Hetero)aryl chloride, bromide, and iodide electrophiles featuring or lacking ortho-substitution, and comprising a range of functionalities (e.g., alkoxy, cyano, fluoro, trifluoromethyl, or alkenyl) and heteroaryl motifs (e.g., pyrrole, pyridine, isoquinoline, quinoline, quinaldine, (benzo)thiophene, benzothiazole, or benzodioxole) were successfully accommodated. Proof-of-principle experiments confirm that other (hetero)aryl methyl ketones can also be employed in such room temperature mono-α-arylations. The established substrate scope is the most extensive reported to date for acetone mono-α-arylation under any conditions, and more generally represents the first room temperature ketone mono-α-arylations employing a structurally diverse set of (hetero)aryl chlorides. Chill out: The first examples of acetone mono-α-arylation at room temperature are described. The substrate scope is the most extensive reported to date for acetone mono-α-arylation under any conditions, and represents the first room temperature ketone mono-α-arylations employing a diverse set of (hetero)aryl chlorides.
