- Using Data Science To Guide Aryl Bromide Substrate Scope Analysis in a Ni/Photoredox-Catalyzed Cross-Coupling with Acetals as Alcohol-Derived Radical Sources
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Ni/photoredox catalysis has emerged as a powerful platform for C(sp2)–C(sp3) bond formation. While many of these methods typically employ aryl bromides as the C(sp2) coupling partner, a variety of aliphatic radical sources have been investigated. In principle, these reactions enable access to the same product scaffolds, but it can be hard to discern which method to employ because nonstandardized sets of aryl bromides are used in scope evaluation. Herein, we report a Ni/photoredox-catalyzed (deutero)methylation and alkylation of aryl halides where benzaldehyde di(alkyl) acetals serve as alcohol-derived radical sources. Reaction development, mechanistic studies, and late-stage derivatization of a biologically relevant aryl chloride, fenofibrate, are presented. Then, we describe the integration of data science techniques, including DFT featurization, dimensionality reduction, and hierarchical clustering, to delineate a diverse and succinct collection of aryl bromides that is representative of the chemical space of the substrate class. By superimposing scope examples from published Ni/photoredox methods on this same chemical space, we identify areas of sparse coverage and high versus low average yields, enabling comparisons between prior art and this new method. Additionally, we demonstrate that the systematically selected scope of aryl bromides can be used to quantify population-wide reactivity trends and reveal sources of possible functional group incompatibility with supervised machine learning.
- Doyle, Abigail G.,Gandhi, Shivaani S.,Jiang, Shutian,Kariofillis, Stavros K.,Martinez Alvarado, Jesus I.,?urański, Andrzej M.
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supporting information
p. 1045 - 1055
(2022/01/19)
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- Discovery of Investigational Drug CT1812, an Antagonist of the Sigma-2 Receptor Complex for Alzheimer's Disease
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An unbiased phenotypic neuronal assay was developed to measure the synaptotoxic effects of soluble Aβ oligomers. A collection of CNS druglike small molecules prepared by conditioned extraction was screened. Compounds that prevented and reversed synaptotox
- Catalano, Susan M.,Huang, Yaodong,Izzo, Nicholas J.,Labarbera, Kelsie M,Limegrover, Colleen S.,Look, Gary C.,Ni, Zhi-Jie,Rehak, Courtney,Rishton, Gilbert M.,Wang, Yingcai,Wu, Xiaodong,Yurko, Raymond,Zhang, Jason
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p. 1389 - 1395
(2021/08/31)
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- ISOINDOLINE COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE
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Isoindoline sigma-2 receptor antagonist compounds, pharmaceutical compositions comprising such compounds, and methods for inhibiting Abeta- associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology are provided.
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- Polystyrene supported Al(OTf)3: A stable, efficient, selective, and reusable catalyst for sulfonylation of arenes with sulfonic acids
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Cross-linked polystyrene supported aluminium triflate (Ps-Al(OTf) 3) was found to be an efficient and chemoselective heterogeneous Lewis acid catalyst for the direct conversion of arenes to sulfones using sulfonic acids as sulfonylating agents. The solid acid catalyst is stable (as a bench top catalyst) and can be easily recovered and reused without appreciable change in its efficiency.
- Boroujeni, Kaveh Parvanak
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experimental part
p. 1887 - 1890
(2010/11/18)
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- Study of regioselective methanesulfonylation of simple aromatics with methanesulfonic anhydride in the presence of zeolite catalysts
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Regioselective methanesulfonylation of simple aromatics using methanesulfonic anhydride can be achieved over zeolite catalysts. For example, methanesulfonylation of toluene over various cation-exchanged zeolite β catalysts affords higher para-selectivity in the synthesis of methyl tolyl sulfone than standard Friedel Crafts methanesulfonylation utilising aluminium chloride.
- Smith, Keith,Ewart, Gordon M.,El-Hiti, Gamal A.,Randles, Kenneth R.
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p. 3150 - 3154
(2007/10/03)
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- Total Synergistic effect between triflic acid and bismuth(IIIr antimony(III) chlorides in catalysis of the Methanesulfonylation of Arenes
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A total synergistic effect between bismuth(III) or antimony(III) chlorides and triflic acid has been observed in the Friedel-Crafts methanesulfonylation of arenes and has resulted in the development of the first efficient catalytic systems usable for the methanesulfonylation of both activated and deactivated arenes. A proposed mechanism to explain the observed effects is also discussed. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Peyronneau, Magali,Boisdon, Marie-Therese,Roques, Nicolas,Mazieres, Stephane,Le Roux, Christophe
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p. 4636 - 4640
(2007/10/03)
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