94347-34-9Relevant articles and documents
Unbalanced-Ion-Pair-Catalyzed Nucleophilic Fluorination Using Potassium Fluoride
Hammond, Gerald B.,Li, Wangbing,Lu, Zhichao,Xu, Bo
supporting information, p. 9640 - 9644 (2021/12/14)
An unbalanced ion pair promoter (e.g., tetrabutylammonium sulfate), consisting of a bulky and charge-delocalized cation and a small and charge-localized anion, greatly accelerates nucleophilic fluorinations using easy handling KF. We also successfully converted an inexpensive and commercially available ion-exchange resin to the polymer-supported ion pair promoter (A26–SO42–), which could be reused after filtration. Moreover, A26–SO42– can be used in continuous flow conditions. In our conditions, water is well-tolerated.
Silver-Promoted Fluorination Reactions of α-Bromoamides
Mizuta, Satoshi,Kitamura, Kanami,Kitagawa, Ayako,Yamaguchi, Tomoko,Ishikawa, Takeshi
supporting information, p. 5930 - 5935 (2021/02/01)
Silver-promoted C?F bond formation in α-bromoamides by using AgF under mild conditions is reported. This simple method enables access to tertiary, secondary, and primary alkyl fluorides involving biomolecular scaffolds. This transformation is applicable to primary and secondary amides and shows broad functional-group tolerance. Kinetics experiments revealed that the reaction rate increased in the order of 3°>2°>1° α-carbon atom. In addition, it was found that the acidic amide proton plays an important role in accelerating the reaction. Mechanistic studies suggested generation of an aziridinone intermediate that undergoes subsequent nucleophilic addition to form the C?F bond with stereospecificity (i.e., retention of configuration). The synthesis of sterically hindered alcohols and ethers by using AgI is also demonstrated. Examples of reactions of α-bromoamides with O nucleophiles are presented.
Enantioconvergent Cu-Catalyzed Radical C-N Coupling of Racemic Secondary Alkyl Halides to Access α-Chiral Primary Amines
Cheng, Jiang-Tao,Dong, Xiao-Yang,Gu, Qiang-Shuai,Li, Zhong-Liang,Liu, Juan,Liu, Xin-Yuan,Luan, Cheng,Wang, Fu-Li,Wang, Li-Lei,Yang, Ning-Yuan,Zhang, Yu-Feng
supporting information, p. 15413 - 15419 (2021/09/30)
α-Chiral alkyl primary amines are virtually universal synthetic precursors for all other α-chiral N-containing compounds ubiquitous in biological, pharmaceutical, and material sciences. The enantioselective amination of common alkyl halides with ammonia is appealing for potential rapid access to α-chiral primary amines, but has hitherto remained rare due to the multifaceted difficulties in using ammonia and the underdeveloped C(sp3)-N coupling. Here we demonstrate sulfoximines as excellent ammonia surrogates for enantioconvergent radical C-N coupling with diverse racemic secondary alkyl halides (>60 examples) by copper catalysis under mild thermal conditions. The reaction efficiently provides highly enantioenrichedN-alkyl sulfoximines (up to 99% yield and >99% ee) featuring secondary benzyl, propargyl, α-carbonyl alkyl, and α-cyano alkyl stereocenters. In addition, we have converted the masked α-chiral primary amines thus obtained to various synthetic building blocks, ligands, and drugs possessing α-chiral N-functionalities, such as carbamate, carboxylamide, secondary and tertiary amine, and oxazoline, with commonly seen α-substitution patterns. These results shine light on the potential of enantioconvergent radical cross-coupling as a general chiral carbon-heteroatom formation strategy.
Comparative conventional and microwave assisted synthesis of heterocyclic oxadiazole analogues having enzymatic inhibition potential
Javid, Jamila,Aziz-ur-Rehman,Abbasi, Muhammad A.,Siddiqui, Sabahat Z.,Iqbal, Javed,Virk, Naeem A.,Rasool, Shahid,Ali, Hira A.,Ashraf, Muhammad,Shahid, Wardah,Hussain, Safdar,Ali Shah, Syed A.
, p. 93 - 110 (2020/10/06)
A comparative microwave assisted and conventional synthetic strategies were applied to synthesize heterocyclic 1,3,4-oxadiazole analogues as active anti-enzymatic agents. Green synthesis of compound 1 was achieved by stirring 4-methoxybenzenesulfonyl chloride (a) and ethyl piperidine-4-carboxylate (b). Compound 1 was converted into respective hydrazide (2) by hydrazine and then into 1,3,4-oxadiazole (3) by CS2 on reflux. The electrophiles, N-alkyl/aralkyl/aryl-2-bromopropanamides (6a–p) were synthesized and converted to N-alkyl/aralkyl/aryl-2-propanamide derivatives (7a–p) by reaction with 3 under green chemistry. Microwave assisted method was found to be effective relative to conventional method. 13C-NMR, 1H-NMR and IR techniques were availed to corroborate structures of synthesized compounds and then subjected to screening against lipoxygenase (LOX), α-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. A number of compounds presented better potential against these enzymes. The most active compounds against LOX and α-glucosidase enzymes were subjected to molecular docking study to explore their interactions with the active sites of the enzymes.
Visible-Light-Driven Aryl Migration and Cyclization of α-Azido Amides
Liang, Siyu,Wei, Kaijie,Lin, Yajun,Liu, Tuming,Wei, Dian,Han, Bing,Yu, Wei
supporting information, p. 4527 - 4531 (2021/06/28)
This paper reports two new visible-light-promoted radical reactions of α-azido amides. By catalysis of [Ir(ppy)2(dtbbpy)]PF6 with i-Pr2NEt as the reducing agent, N-aryl α-azido tertiary amides were first converted to the corresponding aminyl radicals through reduction of the azido group; the aminyl radicals then underwent N-to-N aryl migration to give α-anilinyl-functionalized amides. α-Azido secondary amides, on the other hand, reacted with the solvent ethanol and i-Pr2NEt to afford the imidazolinone products.
A transition metal-free approach to a regioselective total synthesis of the natural product derivative 6-methylellipticine, a potent anticancer agent
Lin, Song-Bo,Wang, Wan-Wan,Meng, Jin-Peng,Li, Xi-Wang,Wu, Jun,Sun, Xiao-Ling
supporting information, (2019/11/26)
A transition metal-free and regioselective total synthesis of 6-methylellipticine, a potent anticancer agent, was developed. This synthetic approach mainly involved two key reactions: a direct amination of multi-functional phenol via an alkylation-Smiles
Enantioselective Palladium-Catalyzed Cross-Coupling of α-Bromo Carboxamides and Aryl Boronic Acids
Li, Bowen,Li, Tiejun,Aliyu, Muinat A.,Li, Zhen Hua,Tang, Wenjun
supporting information, p. 11355 - 11359 (2019/07/12)
We herein report an enantioselective palladium-catalyzed cross-coupling between α-bromo carboxamides and aryl boronic acids, generating a series of chiral α-aryl carboxamides in good yields and excellent enantioselectivities. The development of a chiral P,P=O ligand was critical in overcoming the second transmetalation issue and allows the first asymmetric palladium-catalyzed coupling of α-bromo carbonyl compounds.
Switchable Smiles Rearrangement for Enantioselective O-Aryl Amination
Chang, Xihao,Zhang, Qinglin,Guo, Chang
supporting information, p. 4915 - 4918 (2019/06/27)
Asymmetric assembly of atropisomeric anilines from abundant and readily available precursors is one of the most challenging but valuable processes in organic synthesis. The use of highly efficient Smiles rearrangement to accomplish switchable enantioselec
A novel five-step synthetic route to 1,3,4-oxadiazole derivatives with potent α-glucosidase inhibitory potential and their in silico studies
Iftikhar, Muhammad,Shahnawaz,Saleem, Muhammad,Riaz, Naheed,Aziz-ur-Rehman,Ahmed, Ishtiaq,Rahman, Jameel,Ashraf, Muhammad,Sharif, Muhammad S.,Khan, Shafi U.,Htar, Thet T.
, (2019/11/03)
A series of new N-aryl/aralkyl derivatives of 2-methyl-2-{5-(4-chlorophenyl)-1,3,4-oxadiazole-2ylthiol}acetamide were synthesized by successive conversions of 4-chlorobenzoic acid (a) into ethyl 4-chlorobenzoate (1), 4-chlorobenzoylhydrazide (2) and 5-(4-chlorophenyl)-1,3,4-oxadiazole-2-thiol (3), respectively. The required array of compounds (6a–n) was obtained by the reaction of 1,3,4-oxadiazole (3) with various electrophiles (5a–n) in the presence of DMF (N,N-dimethylformamide) and sodium hydroxide at room temperature. The structural determination of these compounds was done by infrared, 1H-NMR (nuclear magnetic resonance), 13C-NMR, electron ionization mass spectrometry, and high-resolution electron ionization mass spectrometry analyses. All compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 6a, 6c–e, 6g, and 6i were found to be promising inhibitors of α-glucosidase with IC50 values of 81.72 ± 1.18, 52.73 ± 1.16, 62.62 ± 1.15, 56.34 ± 1.17, 86.35 ± 1.17, 52.63 ± 1.16 μM, respectively. Molecular modeling and ADME (absorption, distribution, metabolism, excretion) predictions supported the findings. The current synthesized library of compounds was achieved by utilizing very common raw materials in such a way that the synthesized compounds may prove to be promising drug leads.
Microwave-assisted synthesis of triazole derivatives conjugated with piperidine as new anti-enzymatic agents
Abbasi, Muhammad A.,Ali Shah, Syed A.,Htar, Thet T.,Iqbal, Javed,Khalid, Hira,Khan, Shafi U.,Laulloo, Sabina J.,Rasool, Shahid,Rehman, Aziz-ur-,Siddiqui, Sabahat Z.,Virk, Naeem A.
, (2020/01/25)
The current study was aimed for the study of piperidine-based triazole compounds for their biological potential against various enzymes. A novel library of compounds, 9a-r, having piperidine, 1,2,4-triazole, and propanamides was synthesized through consecutive steps including the formation of sulfonamide, hydrazide, 1,2,4-triazole, and thio-ether. Initially, 4-methoxybenzenesulfonyl chloride (1) and ethyl isonipecotate (2) were utilized to develop ethyl 1-(4-methoxyphenylsulfonyl)-4-piperidinecarboxylate (3). The product 3 was converted into respective hydrazide (4) which was further cyclized into 1,2,4-triazole (5) nucleus. A series of propanamides, 8a-r, were synthesized from different amines, 6a-r. These electrophiles, 8a-r, were reacted with compound 5 under conventional and microwave-assisted protocols to acquire the library of hybrids, 9a-r. The structural confirmations were availed by 1H-NMR, 13C-NMR, and IR techniques. The whole series was evaluated for biological potential against acetylcholinesterase (AChE) and α-glucosidase enzymes. The biological evaluation ranges low to high in potential for different compounds based on the structural variations of synthesized compounds. Almost all the compounds remained active against both the enzymes except a few ones. The bovine serum albumin (BSA) binding study demonstrated the flow of drug in the body, and the docking study explained the interactions responsible for active behavior of synthesized compounds.
