Regio‐ and Enantioselective Synthesis of Allylic Fluorides by Electrophilic Fluorodesilylation of Allyl Silanes

Greedy, Benjamin; Paris, Jean‐Marc; Vidal, Thierry; Gouverneur, Véronique

doi:10.1002/ange.200351405

Cited by 43 publications

(30 citation statements)

References 33 publications

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“…The conformational differences appear even more marked for the minor isomer (À)-8 b. This was studied in both CDCl 3 and C 6 D 6 , the latter removing the troublesome coincidence of H 5 anti did share a large value of 9.1 Hz. In addition,…”

Section: Introductionmentioning

confidence: 97%

“…Noteworthy exceptions are the fluorinated analogues of shikimic acids, which are of relevance as potential antifungal, antibacterial and antiparasitic agents. [4] On the basis of relevant precedent from our laboratory, [5] we reasoned that compounds of general structure I (Scheme 1) could be prepared by diastereoselective electrophilic fluorodesilylation of the corresponding enantioenriched allylsilanes. A known catalytic asymmetric desymmetrization process will enable the construction of the starting enantioenriched dihydroxylated cyclic allylsilanes.…”

Section: Introductionmentioning

confidence: 99%

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Sequential Desymmetrization–Fluorination: Enantioselective Synthesis of Fluorinated Cyclitols

Purser

Odell

Claridge

et al. 2006

Chemistry A European J

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An asymmetric synthesis of enantioenriched, highly functionalized fluorinated carbocycles has been developed based on an enantioselective Sharpless dihydroxylation of cyclohexadienylsilanes, combined with a diastereoselective electrophilic fluorodesilylation. Several parameters define the level of diastereocontrol for the fluorination step. These include the relative stereochemistry of the starting endocyclic allylsilanes and the structural features of the reactants. As expected for an S(E)2' mechanism, the fluorodesilylation occurred with clean transposition of the double bond, with the attack of the electrophilic fluorinating agent taking place preferentially anti to the silyl group. For the fluorination step, the best selectivities were observed for the monocyclic anti,syn benzyl-protected precursors and for the syn,syn starting allylsilane. Full NMR spectroscopic analysis of the fluorinated monocyclic compounds, which possess an endocyclic double bond flanked by two electronegative groups (the methoxy group and the fluorine substituent) revealed that a subtle combination of steric (1,3-axial/pseudoaxial interaction) and stereoelectronic effects (pi-sigma* interaction) favours the preferential conformers featuring the methoxy group in a pseudoaxial position.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Sequential Desymmetrization–Fluorination: Enantioselective Synthesis of Fluorinated Cyclitols

Purser

Odell

Claridge

et al. 2006

Chemistry A European J

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“…We reported that enantioenriched allylic fluorides can be prepared using a reagent-controlled enantioselective fluorodesilylation of prochiral allylsilanes, affording fluorinated carbocycles with a single stereogenic center. [5] In pursuit of a general strategy for the enantioselective synthesis of fluorinated sixmembered carbocycles featuring multiple stereocenters, one of which is fluorinated, it is tempting to resort to the DielsAlder reaction using a monofluorinated diene [6] or dienophile (Scheme 1). [7] However, an asymmetric catalytic approach has yet to be developed, not least because of reactivity and selectivity issues, and the need to prepare the fluorinated reactants with perfect control of their E/Z geometry.…”

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confidence: 99%

A Concise Synthesis of Enantioenriched Fluorinated Carbocycles

et al. 2007

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“…As a compromise of both yield and enantioselectivity, a catalyst loading of 15 mol % was selected for the ensuing study. Lowering the reaction temperature to 0 8C brought no improvement in enantioselectivity, but led to a decrease in the yield and a prolonged reaction time ( [8][9][10][11]. Although higher ee values were obtained in Et 2 O or methyl tert-butyl ether (MTBE), the yields were markedly diminished probably due to the poor solubility of NFSI in these two solvents (Table 2, entries 12 and 15).…”

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confidence: 91%

“…[8,9] Our group has developed a onepot tandem reaction for the synthesis of fluorinated flavanones, from b-ketoesters and aldehydes, with excellent diastereoselectivities.…”

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confidence: 99%

Asymmetric Synthesis of Fluorinated Flavanone Derivatives by an Organocatalytic Tandem Intramolecular Oxa‐Michael Addition/Electrophilic Fluorination Reaction by Using Bifunctional Cinchona Alkaloids

Wang

Cui

Chai

et al. 2009

Chemistry A European J

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Flavanones are a large family of natural products with many important biological activities, such as antitumor and anti-inflammatory properties. [1, 2] However, despite intensive research devoted to the synthesis of flavanone derivatives, [3] only a limited number of methods, particularly catalytic asymmetric methods, are available for the asymmetric synthesis of this class of compound.[4] Structurally, the asymmetric, intramolecular oxa-Michael addition reaction of a phenol to chalcone would provide an easy access to chiral flavanones due to the ready availability of the starting materials. However, it was not until 2007 that a breakthrough based on this strategy, by using an organocatalytic method, was accomplished, by Scheidt and co-workers, [4d] probably due to the low reactivity of the substrates. They addressed this challenge by utilizing an activated, unsaturated ketone, 1, as the substrate and bifunctional chiral thioureas as catalysts (Scheme 1). Recently, Feng and co-workers [4g] reported a metal-catalyzed version of the same reaction employing chiral N,N'-dioxide nickel(II) complexes with excellent results. In view of these results, there is still the potential for the development of new organocatalysts to effect an asymmetric intramolecular oxa-Michael addition as a route to synthesize chiral flavanones.On the other hand, the introduction of a fluorine atom into a compound often results in important changes in its biological activity, which can lead to potential applications in medicinal chemistry and the pharmaceutical industry. [5] One of the most challenging subjects in the field of synthetic fluorine chemistry is the enantioselective construction of the C À F bond at a stereogenic carbon center.[6] Since the first asymmetric fluorination reagents were reported by Differding and Lang [7a] in 1988 and the first catalytic enantioselective fluorination was disclosed by Hintermann and Togni [7b] in 2000, this intriguing field of catalytic asymmetric fluorination has been blooming. [8,9] Our group has developed a onepot tandem reaction for the synthesis of fluorinated flavanones, from b-ketoesters and aldehydes, with excellent diastereoselectivities.[10] On the basis of these results, we envisaged that by using an appropriate bifunctional catalyst, an organocatalytic, asymmetric, intramolecular oxa-Michael addition of 1 would produce enantioenriched 2, which could then be subjected to electrophilic fluorination to provide novel, chiral, fluorinated flavanone derivatives (Scheme 1). Herein, we report the details of this research.Cinchona alkaloids and their derivatives were selected as catalysts to be investigated due to their easy availability and well-documented power as bifunctional organocatalysts in

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Regio‐ and Enantioselective Synthesis of Allylic Fluorides by Electrophilic Fluorodesilylation of Allyl Silanes

Cited by 43 publications

References 33 publications

Sequential Desymmetrization–Fluorination: Enantioselective Synthesis of Fluorinated Cyclitols

Sequential Desymmetrization–Fluorination: Enantioselective Synthesis of Fluorinated Cyclitols

A Concise Synthesis of Enantioenriched Fluorinated Carbocycles

Asymmetric Synthesis of Fluorinated Flavanone Derivatives by an Organocatalytic Tandem Intramolecular Oxa‐Michael Addition/Electrophilic Fluorination Reaction by Using Bifunctional Cinchona Alkaloids

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