- Functionalization of α-C(sp3)?H Bonds in Amides Using Radical Translocating Arylating Groups
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α-C?H arylation of N-alkylamides using 2-iodoarylsulfonyl radical translocating arylating (RTA) groups is reported. The method allows the construction of α-quaternary carbon centers in amides. Various mono- and disubstituted RTA-groups are applied to the arylation of primary, secondary, and tertiary α-C(sp3)?H-bonds. These radical transformations proceed in good to excellent yields and the cascades comprise a 1,6-hydrogen atom transfer, followed by a 1,4-aryl migration with subsequent SO2 extrusion.
- Radhoff, Niklas,Studer, Armido
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supporting information
p. 3561 - 3565
(2021/01/04)
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- Isothiourea-Catalyzed Acylative Kinetic Resolution of Tertiary α-Hydroxy Esters
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A highly enantioselective isothiourea-catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently-developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous-flow process using a polymer-supported variant of the catalyst.
- Greenhalgh, Mark D.,Laina-Martín, Víctor,Neyyappadath, Rifahath M.,Qu, Shen,Smith, Andrew D.,Smith, Samuel M.
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supporting information
p. 16572 - 16578
(2020/09/09)
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- 2-Amino-5,6-difluorophenyl-1 H-pyrazole-Directed PdII Catalysis: Arylation of Unactivated β-C(sp3)-H Bonds
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Palladium-catalyzed arylation of unactivated β-C(sp3)-H bonds in carboxylic acid derivatives with aryl iodides is described for the first time using 2-amino-5,6-difluorophenyl-1H-pyrazole as an efficient and readily removable directing group. Two fluoro groups are installed at the 5- and 6-position of the anilino moiety in 2-aminophenyl-1H-pyrazole, clearly enhancing the directing ability of the auxiliary. In addition, the protocol employs Cu(OAc)2/Ag3PO4 (1.2/0.3) as additives, evidently reducing the stoichiometric amount of expensive silver salts. Furthermore, this process exhibits high β-site selectivity, compatibility with diverse substrates containing α-hydrogen atoms, and excellent functional group tolerance.
- Yang, Jinyue,Fu, Xiaopan,Tang, Shibiao,Deng, Kezuan,Zhang, Lili,Yang, Xianjin,Ji, Yafei
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p. 10221 - 10236
(2019/08/20)
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- The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing
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New drugs for neglected tropical diseases such as human African trypanosomiasis (HAT) are needed, yet drug discovery efforts are not often focused on this area due to cost. Target repurposing, achieved by the matching of essential parasite enzymes to those human enzymes that have been successfully inhibited by small molecule drugs, provides an attractive means by which new drug optimization programs can be pragmatically initiated. In this report we describe our results in repurposing an established class of human Aurora kinase inhibitors, typified by danusertib (1), which we have observed to be an inhibitor of trypanosomal Aurora kinase 1 (TbAUK1) and effective in parasite killing in vitro. Informed by homology modeling and docking, a series of analogs of 1 were prepared that explored the scope of the chemotype and provided a nearly 25-fold improvement in cellular selectivity for parasite cells over human cells.
- Ochiana, Stefan O.,Pandarinath, Vidya,Wang, Zhouxi,Kapoor, Rishika,Ondrechen, Mary Jo,Ruben, Larry,Pollastri, Michael P.
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p. 777 - 784
(2013/05/09)
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- Aza-oxindole synthesis by oxidative coupling of Csp 2-H and Csp3-H centers
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A Cu(ii) mediated oxidative Csp2-H and C sp3-H coupling protocol gives access to aza-oxindoles in good to excellent yield in the presence of NaOtBu as base and toluene as solvent. The Royal Society of Chemistry
- Dey, Chandan,Kuendig, E. Peter
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supporting information; experimental part
p. 3064 - 3066
(2012/04/17)
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- Aza-oxindole synthesis via base promoted Truce-Smiles rearrangement
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A novel efficient NaOtBu-mediated protocol for the synthesis of 3,3-disubstituted aza-oxindoles proceeds via a Truce-Smiles rearrangement- cyclisation pathway.
- Dey, Chandan,Katayev, Dmitry,Ylijoki, Kai E. O.,Kuendig, E. Peter
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supporting information
p. 10957 - 10959
(2013/01/15)
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- Synthesis of chiral N-heterocyclic carbene ligands with rigid backbones and application to the palladium-catalyzed enantioselective intramolecular α-arylation of amides
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Chiral N-heterocyclic carbene (NHC) ligands having a 2,2′- bisquinoline-based C2 symmetric skeleton were developed. The ligands exhibited good enantioselectivity in palladium-catalyzed intramolecular α-arylation of amides to give 3,3-disubsituted oxindoles.
- Liu, Lantao,Ishida, Naoki,Ashida, Shinji,Murakami, Masahiro
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supporting information; experimental part
p. 1666 - 1669
(2011/05/11)
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- Oxindole synthesis by direct coupling of Csp2-H and C sp3-H centers
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(Chemical Equation Presented) An sp2/sp3 get-together: A novel and efficient method can be used to synthesize 3,3-disubstitued oxindoles by the direct intramolecular oxidative coupling of an aryl Csp2-H and a Csp3-H center (see scheme; DMF = N,N-dimethylformamide).
- Jia, Yi-Xia,Kuendig, E. Peter
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supporting information; experimental part
p. 1636 - 1639
(2009/06/30)
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- An investigation into the electrophilic cyclisation of N-acyl-pyrrolidinium ions: A facile synthesis of Pyrrolo-tetrahydroisoquinolones and Pyrrolo-benzazepinones
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The triflic acid-mediated cyclisation of N-arylmethyl- and N-arylethyl-acylpyrrolidinium ions gave moderate to good yields of pyrrolo-tetrahydroisoquinolones and pyrrolo-benzazepinones respectively. Electron-donating R substituents enhanced the rate of reaction and gave higher yields than electron-withdrawing substituents. Substituents on the methyl or ethyl chain in general enhanced the reaction, unless sterically encumbered. The equivalent acylpiperidinium ions cyclised much slower and in lower yield.
- King, Frank D.,Aliev, Abil E.,Caddick, Stephen,Copley, Royston C. B.
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experimental part
p. 3561 - 3571
(2010/01/06)
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- Bulky chiral carbene ligands and their application in the palladium- catalyzed asymmetric intramolecular α-arylation of amides
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(Chemical Equation Presented) Bring on the big cats: New, C 2-symmetric bulky N-heterocyclic carbene ligands bring major improvements in the palladium-catalyzed asymmetric intramolecular α-arylation of amides to give oxindoles (see picture, dba=trans,trans- dibenzylideneacetone), which are formed in high yield and excellent enantiomeric purity.
- Kuendig, E. Peter,Seidel, Thomas M.,Jia, Yi-Xia,Bernardinelli, Gerald
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p. 8484 - 8487
(2008/09/18)
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- Chemoselective rhodium-carbenoid reaction with the aromatic nucleus: An efficient methodology for 2-indanones, 2- Tetralones and 2-benzosuberones and its application in the synthesis of (±)-ar-Himachalene
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Rhodium-carbenoid species derived from rhodium acetate- catalyzed decomposition of aryl alkyl α- diazoke-tones have been shown to display a chemoselective addition into the aromatic nucleus, instead of insertion into an aliphatic C-H site. The synthetic u
- Sudrik,Nanjundiah,Sonawane
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p. 1103 - 1112
(2007/10/03)
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