A Diels–Alder approach to the enantioselective construction of fluoromethylated stereogenic carbon centers

Shibatomi, Kazutaka; Kobayashi, Fumito; Narayama, Akira; Fujisawa, Ikuhide; Iwasa, Seiji

doi:10.1039/c1cc15889a

Cited by 45 publications

(16 citation statements)

References 39 publications

(2 reference statements)

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“…Most recently, Shibatomi et al. reported highly enantioselective Diels–Alder reactions of β‐CF 2 H‐substituted acrylates 85 with cyclopentadiene or furan derivatives 86 , catalyzed by 10–30 mol % of Lewis acid 87 , to prepare gem ‐difluoroalkyl‐substituted cyclohexenes 88 in almost enantiopure form (Scheme ) 33a. The endo / exo selectivity was greatly influenced by the substituents of the dienes.…”

Section: Catalytic Asymmetric Methodsmentioning

confidence: 99%

Catalytic Asymmetric Construction of Stereogenic Carbon Centers that Feature a gem‐Difluoroalkyl Group

Liu

Zhou

2013

Asian J Org Chem

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gem-Difluoroalkyl groups, characterized as a gem-difluoromethylene group substituted by a hydrogen atom or an alkyl or other functional group, are not only valuable for the modulation of the properties of organic compounds, but are also useful for the synthesis of various fluorine-containing compounds. Currently, the catalytic asymmetric construction of stereogenic carbon centers that feature a gem-difluoroalkyl group is in its infancy. This Focus Review summarizes the latest achievements and discusses the difficulties and challenges in this field. Scheme 1. Structural difference between a CF 3 group and a difluoroalkyl group. FG = functional group. Scheme 2. The presence of gem-difluoroalkyl groups in important compounds. Scheme 13. The catalytic asymmetric addition of TMSCF 2 SO 2 Ph to aldehydes. TBAF = tetrabutylammonium fluoride. Scheme 14. The catalytic asymmetric addition of TMSCF 2 SePh to ketones. Ar = 3,5-(CF 3 ) 2 C 6 H 3 . Scheme 15. The asymmetric hydrogenation of a-CF 2 R ketimines. Bn = benzyl. Scheme 16. The Mannich reaction of a-difluoromethyl aldimines 69.

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Section: Catalytic Asymmetric Methodsmentioning

confidence: 99%

Catalytic Asymmetric Construction of Stereogenic Carbon Centers that Feature a gem‐Difluoroalkyl Group

Liu

Zhou

2013

Asian J Org Chem

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“…In parallel, this Diels-Alder approach was applied to other fluoroalkylated cyclohexenes as nearly pure enantiomers, greatly extending their synthetic utility (Scheme 15). [52] Recently, Sun et al implemented the two-step synthesis of a densely substituted tetrahydrofuran (95 % ee) containing a quaternary trifluoromethylated stereogenic center by means of a novel NHC-catalyzed asymmetric a-aldol reaction of racemic g-reducible enals and trifluoropyruvates. [53] 2.3.6.…”

Section: Chiral Trifluoromethylated Pyrrolidines (Cf 3 -Pyrrolidines)mentioning

confidence: 99%

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF₃ Stereogenic Center

Huang

Yang

Chen

et al. 2015

Chemistry A European J

132

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Given the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost-effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo- and organometal-catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles.

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“…Bergmann et al 15 and later Liu and coworkers 16 used cyanation of, respectively, an epoxide or a geminal chlorofluoro dihalide (Route B) to generate a fluorohydrin-functionalized nitrile intermediate which was then converted into the ethyl ester 4f by ethanolysis. A dihalide precursor was also employed in a synthesis of 4f by Shibatomi et al (route C); 17 a Claisen condensation of ethyl acetate with 2chloro-2-fluoroacetic acid resulted in a -keto dihalide that was then subjected to two reduction steps, a borohydridemediated reduction of the keto moiety followed by reductive dehalogenation with tributyltin hydride to achieve the final fluorinated ester 4f.…”

Section: Paper Syn Thesismentioning

confidence: 99%

Synthesis of 2-Fluoroacetoacetic Acid and 4-Fluoro-3-hydroxybutyric Acid

2019

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The butyric acid scaffold is the base structure of several human metabolites that serve diverse and prominent biochemical roles including as oxidative sources of cellular energy and as substrates for biosynthesis. Derivatization of metabolites through incorporation of fluorine often alters bioactivity and can facilitate detection and analysis by nuclear magnetic resonance or positron emission tomography depending upon the fluorine isotope employed. We describe the synthesis of two new fluorinated butyric acids (and three related esters) that are derivatives of the metabolites acetoacetic acid and 3-hydroxybutyric acid. 4-Fluoro-3-hydroxybutyric acid is prepared from epoxy ester precursors via ring opening by triethylamine trihydrofluoride. 2-Fluoroacetoacetic acid is prepared by electrophilic fluorination of an acid-labile β-keto ester. The gradual pH-dependent decarboxylation of 2-fluoroacetoacetic acid is investigated by 19F NMR spectroscopy.

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A Diels–Alder approach to the enantioselective construction of fluoromethylated stereogenic carbon centers

Cited by 45 publications

References 39 publications

Catalytic Asymmetric Construction of Stereogenic Carbon Centers that Feature a gem‐Difluoroalkyl Group

Catalytic Asymmetric Construction of Stereogenic Carbon Centers that Feature a gem‐Difluoroalkyl Group

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF₃ Stereogenic Center

Synthesis of 2-Fluoroacetoacetic Acid and 4-Fluoro-3-hydroxybutyric Acid

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A Diels–Alder approach to the enantioselective construction of fluoromethylated stereogenic carbon centers

Cited by 45 publications

References 39 publications

Catalytic Asymmetric Construction of Stereogenic Carbon Centers that Feature a gem‐Difluoroalkyl Group

Catalytic Asymmetric Construction of Stereogenic Carbon Centers that Feature a gem‐Difluoroalkyl Group

Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF3 Stereogenic Center

Synthesis of 2-Fluoroacetoacetic Acid and 4-Fluoro-3-hydroxy­butyric Acid

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Catalytic Asymmetric Synthesis of Enantioenriched Heterocycles Bearing a CCF₃ Stereogenic Center

Synthesis of 2-Fluoroacetoacetic Acid and 4-Fluoro-3-hydroxybutyric Acid