Organocatalytic Asymmetric Fluorination of 4‐Substituted Isoxazolinones

Zhang, Huanrui; Wang, Baomin; Cui, Longchen; Bao, Xiaoze; Qü, Jingping; Song, Yuming

doi:10.1002/ejoc.201500650

Cited by 3 publications

(6 citation statements)

References 17 publications

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“…The enantiopure fluorinated heterocycles bearing a fluorine-containing quaternary stereogenic center 95 were prepared in good yields and good enantioselectivities (up to 91% yield, 85% ee). 139 Meanwhile, to demonstrate the practical utility of the asymmetric fluorination protocol, the 4-fluoroisoxazolinone derivatives 95a can be provided with high enantioselectivity (>99% ee) after a single recrystallization from gram-scale products which had been generated in 85% yield and 80% ee under optimized reaction conditions (Scheme 19).…”

Section: Modern Methods For Construction Of Quaternary C–f Stereogenimentioning

confidence: 99%

Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

et al. 2018

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New methods for preparation of tailor-made fluorine-containing compounds are in extremely high demand in nearly every sector of chemical industry. The asymmetric construction of quaternary C−F stereogenic centers is the most synthetically challenging and, consequently, the least developed area of research. As a reflection of this apparent methodological deficit, pharmaceutical drugs featuring C−F stereogenic centers constitute less than 1% of all fluorine-containing medicines currently on the market or in clinical development. Here we provide a comprehensive review of current research activity in this area, including such general directions as asymmetric electrophilic fluorination via organocatalytic and transition-metal catalyzed reactions, asymmetric elaboration of fluorine-containing substrates via alkylations, Mannich, Michael, and aldol additions, cross-coupling reactions, and biocatalytic approaches. CONTENTS

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Section: Modern Methods For Construction Of Quaternary C–f Stereogenimentioning

confidence: 99%

Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

et al. 2018

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“…The analytical data is in accordance to the literature. 18 Bigger scale experiment: 0.760 mmol (250.0 mg) of 1d was used. White solid (302.9 mg, 0.654 mmol, 86%, 90% ee).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…The analytical data is in accordance to the literature. 18 (R)-(+)-4-Fluoro-4-(4-methylbenzyl)-3-phenylisoxazol-5(4H)-one (2i). 0.105 mmol of 1i was used.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

“…17a The first enantioselective fluorination was reported in 2015 by Song et al 4-Fluorinated products were accessible with 75−85% ee using a bridged biscinchona-alkaloid derived catalyst (10 mol %) at −60 °C (Scheme 1, middle). 18 Despite the evident potential of chiral isoxazolinones to serve as β-amino acid precursors, this strategy was never reported for the preparation of enantioenriched β-amino acids.…”

Section: ■ Introductionmentioning

confidence: 99%

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Enantioenriched γ-Aminoalcohols, β-Amino Acids, β-Lactams, and Azetidines Featuring Tetrasubstituted Fluorinated Stereocenters via Palladacycle-Catalyzed Asymmetric Fluorination of Isoxazolinones

et al. 2021

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Enantiopure fluorine containing β-amino acids are of large biological and pharmaceutical interest. Strategies to prepare β-amino acid derivatives possessing a F-containing tetrasubstituted stereocenter at the α-C atom in a catalytic asymmetric sense are rare, in particular using an enantioselective electrophilic C–F bond formation. In the present study, a highly enantioselective palladacycle-catalyzed fluorination of isoxazolinones was developed. It is demonstrated that isoxazolinones are useful precursors toward enantiopure β-amino acid derivatives by diastereo- and chemoselective reduction. The formed γ-aminoalcohols served as valuable precursors toward β-amino acids, β-amino acid esters, and β-lactams, all featuring tetrasubstituted fluorinated stereocenters. In addition, by this work, enantioenriched fluorinated azetidines were accessible for the first time.

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“…The asymmetric fluorination of 4substituted isoxazolinones can also promote by a bis-cinchona alkaloid catalyst (Scheme 17, Eq. 2) [32].…”

Section: Catalytic Enantioselective Electrophilic A-fluorination Of Kmentioning

confidence: 99%

NFSI and Its Analogs Electrophilic Fluorination for Preparing Alkyl Fluorides

Wang¹,

Ma²

2017

Fluorination

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Organocatalytic Asymmetric Fluorination of 4‐Substituted Isoxazolinones

Abstract: In the original paper, [1] ee [%] [c]

Cited by 3 publications

References 17 publications

Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

Modern Approaches for Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers: Synthetic Challenges and Pharmaceutical Needs

Enantioenriched γ-Aminoalcohols, β-Amino Acids, β-Lactams, and Azetidines Featuring Tetrasubstituted Fluorinated Stereocenters via Palladacycle-Catalyzed Asymmetric Fluorination of Isoxazolinones

NFSI and Its Analogs Electrophilic Fluorination for Preparing Alkyl Fluorides

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