- 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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- Nickel-Catalyzed Favorskii-Type Rearrangement of Cyclobutanone Oxime Esters to Cyclopropanecarbonitriles
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A nickel-catalyzed base-promoted rearrangement of cyclobutanone oxime esters to cyclopropanecarbonitriles was developed. The ring opening of cyclobutanone oxime esters occurs at the sterically less hindered side. A base-promoted nickelacyclobutane intermediate, formed in situ, is assumed to be involved in the formation of the product.
- Fang, Ping,Mei, Tian-Sheng,Shuai, Bin
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p. 1637 - 1641
(2021/10/02)
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- Chiral Bidentate Boryl Ligand Enabled Iridium-Catalyzed Enantioselective C(sp3)-H Borylation of Cyclopropanes
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We herein report an Ir-catalyzed enantioselective C(sp3)-H borylation of cyclopropanecarboxamides using a chiral bidentate boryl ligand for the first time. A variety of substrates with α-quaternary carbon centers could be compatible in this reaction to provide β-borylated products with good to excellent enantioselectivities. We have also demonstrated that the borylated products can be used as versatile precursors engaging in stereospecific transformations of C-B bonds, including the synthesis of a bioactive compound Levomilnacipran.
- Shi, Yongjia,Gao, Qian,Xu, Senmiao
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supporting information
p. 10599 - 10604
(2019/08/28)
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- Electrophilic Bromolactonization of Cyclopropyl Diesters Using Lewis Basic Chalcogenide Catalysts
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An efficient and regioselective electrophilic bromolactonization of cyclopropylmethyl diesters using triphenylphosphine sulfide (Ph3PS) or diphenyl selenide (Ph2Se) as the Lewis basic chalcogenide catalyst has been developed. It was observed that Ph3PS favored the formation of anti-diastereomer and yielded the multi-functional γ-lactones. Interestingly, the diastereoselectivity was reversed when using Ph2Se as a catalyst where the syn-product instead of the anti-product was favored. (Figure presented.).
- Gieuw, Matthew H.,Leung, Vincent Ming-Yau,Ke, Zhihai,Yeung, Ying-Yeung
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supporting information
p. 4306 - 4311
(2018/10/02)
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- Lewis Basic Sulfide Catalyzed Electrophilic Bromocyclization of Cyclopropylmethyl Amide
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A Lewis basic sulfide catalyzed electrophilic bromocyclization of cyclopropylmethyl amide has been developed. The catalytic protocol is applicable to both 1,1- and 1,2-substituted cyclopropylmethyl amides, giving oxazolines and oxazines in good yields and excellent diastereoselectivity.
- Wong, Ying-Chieh,Ke, Zhihai,Yeung, Ying-Yeung
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supporting information
p. 4944 - 4947
(2015/11/03)
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- Cyclopropanation of substituted phenylacetonitriles or phenyl acetates
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The present invention relates to a process for the cyclopropanation with ethylene carbonate or ethylene sulfate of a compound of formula (II): wherein G is -CN or -COOR in which R is a C1-C4 straight or branched alkyl X and Y are independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, R1O- and R1S- wherein R1 is C1-C4 straight or branched alkyl chain.
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Paragraph 0027
(2015/01/18)
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- Efficient cyclopropanation of active methylene compounds. A serendipitous discovery
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Cyclopropanation of active methylene compounds has been achieved in good yields with ethylene carbonate as the cyclopropanating agent in the presence of a simple base.
- Arava, Veera Reddy,Siripalli, Udaya Bhaskara Rao,Dubey, Pramod Kumar
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p. 7247 - 7248
(2007/10/03)
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