Electrophilic and nucleophilic side chain fluorination of para-substituted acetophenones

Fuglseth, Erik; Thvedt, Thor Håkon Krane; Møll, Maria Førde; Hoff, Bård Helge

doi:10.1016/j.tet.2008.05.060

Cited by 34 publications

(17 citation statements)

References 48 publications

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“…The a-fluoroketones 4a-e (Scheme 1) were most conveniently prepared by fluorination of the corresponding trimethylsilyl enol ethers, 2a-e, using Selectfluor TM (1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis-(tetrafluoroborate) [1], while 4f-h were obtained in highest yield by reacting the acetophenones, 1f-h, with Selectfluor TM in methanol. The dimethoxyacetals, 3f-h formed as the major products were hydrolysed using trifluoroacetic acid [1].…”

Section: Resultsmentioning

confidence: 99%

“…The dimethoxyacetals, 3f-h formed as the major products were hydrolysed using trifluoroacetic acid [1]. The ATH of 4a-h were studied using four different catalysts, 5-8, which were prepared by mixing the ruthenium arene complexes, [RuCl 2 (p-cymene)] 2 and [RuCl 2 (mesitylene)] 2 with (R,R)-TsDPEN and (R,R)-TsCYDN, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Due to their somewhat troublesome preparation, fluorinated secondary alcohols have received considerably less attention. We have recently described routes to a-fluorinated ketones, rendering their corresponding alcohols easy accessible [1]. The potential use of such optically enriched fluorinated alcoholic building blocks is vast, and includes among others pharmaceuticals, advanced materials and agrochemicals [2][3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Ruthenium-catalysed asymmetric transfer hydrogenation of para-substituted α-fluoroacetophenones

Fuglseth

Sundby²,

Hoff

2009

Journal of Fluorine Chemistry

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ruthenium-catalysed asymmetric transfer hydrogenation of para-substituted α-fluoroacetophenones

Fuglseth

Sundby²,

Hoff

2009

Journal of Fluorine Chemistry

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“…1-(4-Bromophenyl)-2,2,2-trifluoroethanone 4a was from Apollo, 2,2-difluoro-1-phenylethanone 3c from Alfa Aesar, whereas 2-fluoro-1-phenylethanone 2c was synthesised as described previously. 46,47 …”

Section: Chemicalsmentioning

confidence: 99%

Enantioselectivity, swelling and stability of 4-hydroxyprolinol containing acrylic polymer beads in the asymmetric reduction of ketones

Thvedt¹,

Kristensen²,

Sundby³

et al. 2011

Tetrahedron: Asymmetry

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a b s t r a c tA new 4-hydroxy-a,a-diphenyl-L-prolinol containing polymethacrylate, prepared without chromatography by a large scale adaptable synthesis, has been evaluated as a catalyst in the asymmetric reduction of 1-arylethanones. Using 1-(4-bromophenyl)ethanone as the model substance, the reduction was tested with various borane sources and solvents. The best swellings of the polymer and reactivity were observed in THF using N,N-diethylaniline borane complex as the hydride source. The selectivity in the reduction of 1-(4-bromophenyl)ethanone was found to depend on the substrate concentration and catalyst loading. Using the best conditions identified, a series of 1-arylethanones was reduced to their corresponding enantioenriched secondary alcohols. High rates and ee-values were obtained in the reduction of acetophenones containing electron withdrawing groups in the aromatic ring, whereas a moderate selectivity was the result for products containing electron donating aromatic substituents. Upon recovery of the polymer beads, it was found that vacuum drying led to extensive rupturing, while the bead structure was intact if washed with methanol and air dried at atmospheric pressure. Repeated use of the polymer catalyst gave the product alcohol with a lower 90% ee. Elemental analysis showed this to be due to the loss of the chiral prolinol unit.

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“…[18] The use of Selectfluor as stoichiometric fluorinating agent of ketones has been reported although the substrate scope is limited and low selectivities are observed. [19] To the best of our knowledge, the selective formation of a-fluoro acetals or, alternatively, a-fluoro ketones from alkynes presented here is rather unexplored. [20] In our screening, phenylacetylene (1a) was used as a benchmark substrate.…”

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confidence: 99%

Gold‐Catalyzed Synthesis of α‐Fluoro Acetals and α‐Fluoro Ketones from Alkynes

Haro

Nevado

2010

Adv Synth Catal

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A new method to synthesize a-fluoro acetals and a-fluoro ketones is presented here. In the presence of alcohols and Selectfluor, catalytic amounts of gold selectively transformed alkynes into the corresponding fluorinated acetals or ketones depending on the reaction conditions. This protocol has been applied to both terminal and internal alkynes showing a high degree of chemo-and regioselectivity. The reaction mechanism seems to proceed via two co-existing pathways, since at least partially, the formation of the CA C H T U N G T R E N N U N G (sp 3 ) À F bond in the final products occurs at the metal center.Keywords: alkynes; catalysis; fluorination; gold; hydration Metal complexes of alkynes are important intermediates in many transformations such as 1,n-enyne cyclization, polymerization and metathesis reactions.[1] According to the classical Dewar-Chatt-Duncanson model, [2] the bonding between the metal and the alkyne can be described as a combination of a s-and a p-interaction (by overlap of the p-system of the acetylene with dsp orbitals of the metal and from filled d-orbitals of the metal into p*-orbital of acetylene, respectively). Late transition metals, such as Hg, Cu, Pd, Pt, Au, etc., show a more important s-contribution to the bond with almost no back-donation, thus diminishing the electron density on the alkyne and increasing its susceptibility to a nucleophilic attack.[3] Such a reactivity mode has been thoroughly exploited over the past century. Alkynes, as an abundant hydrocarbon source, have been reported to undergo the addition of C, N, S and O nucleophiles upon p-activation with transition metals.[4] The nucleophilic addition of water or alcohols to alkynes has attracted enormous attention since it represents an excellent way to obtain aldehydes, ketones or their corresponding acetals depending on whether the reaction occurs in a Markownikoff or anti-Markownikoff manner (Scheme 1).[5] Hg(II) was the first metal used to promote the hydration of alkynes in an industrially relevant process for the synthesis of acetaldehyde and crotonaldehyde. [6,7] Soon it became clear that mercury had to be replaced, not only because of its toxicity but also due to its rapid reduction to catalytically inactive Hg(0) species under the reaction conditions.Other metals such as Ag(I),and Os(II) were explored, although the reactions proved to be more limited in scope.[8] In contrast, Pt(II), [9] Au(I) and AuA C H T U N G T R E N N U N G (III) [10] have showed a much better profile in terms of scope, selectivity and catalytic activity. Noticeably, the most active catalysts reported so far are those based on gold, [10c,d,11] which, due to the strong relativistic effects governing its coordination behaviour, is able to activate unsaturated moieties in an unparalleled mild and efficient manner.Our ongoing program is focused on the development of novel methodologies for the construction of molecular complexity triggered by the p-activation ability of gold species.[12] We have recently developed an efficient meth...

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Electrophilic and nucleophilic side chain fluorination of para-substituted acetophenones

Cited by 34 publications

References 48 publications

Ruthenium-catalysed asymmetric transfer hydrogenation of para-substituted α-fluoroacetophenones

Ruthenium-catalysed asymmetric transfer hydrogenation of para-substituted α-fluoroacetophenones

Enantioselectivity, swelling and stability of 4-hydroxyprolinol containing acrylic polymer beads in the asymmetric reduction of ketones

Gold‐Catalyzed Synthesis of α‐Fluoro Acetals and α‐Fluoro Ketones from Alkynes

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