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Véronique Gouverneur

Publications and source records attributed to Véronique Gouverneur.

At least 19 recordsLinked to original sources
PubMed2006

Sequential desymmetrization-fluorination: enantioselective synthesis of fluorinated cyclitols.

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.

Ethers, Cyclic↗
PubMed2006

Enantioselective organocatalytic aldol reaction of ynones and its synthetic applications.

[Structure: see text] For the first time, unmodified ynones were used in organocatalytic asymmetric aldol reactions delivering monoprotected anti-alpha,beta-dihydroxyynones in high yields, dr's up to 19:1, and ee's up to 95%. These products can be either reduced to afford enantioenriched unsaturated anti,anti-triol or cyclized using a novel intramolecular phosphine-catalyzed alpha-addition to the ynone. This organocatalytic sequential aldol-cyclization process provides a concise entry to unusual enantioenriched oxygenated heterocycles, which can be used for subsequent structural manipulations.

Journal Article↗
PubMed2006

Pd(II)-catalyzed cascade Wacker-Heck reaction: chemoselective coupling of two electron-deficient reactants.

A novel palladium(II)-catalyzed oxy-carbopalladation process was developed allowing for the orchestrated union of hydroxy ynones with ethyl acrylate, two electron-deficient reactants. With beta-hydroxy ynones, this cascade Wacker-Heck process gave access to highly functionalized tri- or tetrasubstituted dihydropyranones featuring an unusual dienic system. For diastereomerically pure and for enantioenriched beta-hydroxyynones, these reactions proceed without affecting the stereochemical integrity of the existing stereocenters. In addition, tetrasubstituted furanones can be prepared when alpha-hydroxyynones and ethyl acrylate are used as starting materials. The dihydropyranones and furanones obtained upon cyclization are novel compounds, but structurally related carbohydrate derivatives featuring a similar dienic system have been used as starting materials for the construction of polyannulated products, suggesting that these cascade Pd(II)-mediated oxidative heterocyclizations are of value for various synthetic applications.

Journal Article↗
PubMed2006

Intramolecular hetero-Michael addition of beta-hydroxyenones for the preparation of highly substituted tetrahydropyranones.

Structurally diverse beta-hydroxyenones are shown to undergo nonoxidative 6-endo-trig ring closure to form highly substituted tetrahydropyranones. Amberlyst-15, Al(ClO(4))(3) x 9 H(2)O and [Pd(MeCN)(4)](BF(4))(2) were found to be suitable catalysts for these intramolecular conjugate additions, preventing side reactions, such as dehydration or retroaldolisation. The use of [Pd(MeCN)(4)](BF(4))(2) is particularly effective, as this palladium-mediated reaction is under kinetic control and generates tri- and tetrasubstituted tetrahydropyranones with high levels of diastereocontrol. In the presence of the Lewis acid Al(ClO(4))(3) x 9 H(2)O, the reaction proceeded with a similar level of diastereocontrol; however, in contrast to [Pd(MeCN)(4)](BF(4))(2), this catalyst can promote enolisation. The palladium-mediated reaction was also found to be compatible with an enantioenriched beta-hydroxyenone substrate, giving no loss of enantiopurity upon ring closure. The most distinctive synthetic development to emerge from this new chemistry is the possibility to access tri- and tetrasubstituted 2,6-anti-tetrahydropyranones from anti-aldol precursors. These compounds are particularly difficult to access by using alternative methodologies. Two modes of activation were envisaged for the ring closure, involving metal coordination to either the C=C or C=O functional groups. Experimental results suggest that C=O coordination was the preferred mode of activation for reactions performed in the presence of Al(ClO(4))(3) x 9 H(2)O or [Pd(MeCN)(4)](BF(4))(2).

Alkenes↗
PubMed2006

Synthesis of propargylic fluorides from allenylsilanes.

Allenylsilanes reacted at room temperature in acetonitrile with Selectfluor, an electrophilic fluorinating reagent, to give secondary propargylic fluorides in moderate to good yields; mechanistically, a side-product resulting from a 1,2-silyl shift testifies to the presence of a cationic intermediate.

Journal Article↗
PubMed2006

Enantioselective synthesis of a key "A-ring" intermediate for the preparation of 1alpha-fluoro vitamin D3 analogues.

1Alpha-fluoro A-ring dienol 2, a useful building block for the preparation of fluorinated vitamin D3 analogues, was synthesized in eight steps from 4-{[tert-butyldimethylsilyl]oxy}cyclohexanone. The most distinctive synthetic development to emerge from this new synthesis is an unprecedented substrate-controlled diastereoselective fluorodesilylation of an advanced dienylsilane intermediate. This is the first enantioselective route to compound 2 relying on the use of an electrophilic fluorinating reagent.

Cholecalciferol↗
PubMed2006

Catalytic asymmetric fluorinations.

The appearance of structurally diverse fluorinating reagents displaying a large spectrum of reactivity has been critical to the development of the catalytic asymmetric fluorination processes known to date. In this article, we discuss how this area of research emerged and which strategies have allowed for the successful development of both nucleophilic and electrophilic catalytic enantioselective fluorinations. We also present the fundamental understanding of catalytic activity and enantioselectivity for the most efficient processes and highlight the first synthetic application with the preparation of a complex fluorinated target.

Catalysis↗
PubMed2005

Diastereoselective ring-closing metathesis: synthesis of P-stereogenic phosphinates from prochiral phosphinic acid derivatives.

[reaction: see text] The preparation of phosphorus-containing trienes featuring two diastereotopic vinyl moieties followed by a diastereoselective ring-closing metathesis is described. This methodology allowed for the synthesis of novel highly functionalized P-stereogenic heterocycles featuring both an exo- and an endocyclic double bond. An investigation into the factors influencing the diastereochemical outcome of the ring-closing metathesis is also presented, revealing that the geometry of the double bonds conjugated to phosphorus is important and that 1,3-stereoinduction is superior to 1,4-stereoinduction for these reactions.

Journal Article↗
PubMed2005

Electrophilic fluorination of organosilanes.

The fluorination of organosilanes with the silyl groups directly attached or adjacent to an aryl or alkenyl group has been only very recently examined despite the fact that the corresponding fluorinated products are synthetically useful building blocks. In these reactions, the silyl group enhances the reactivity of the pi-nucleophile and controls the sense of regiochemistry upon addition of the electrophilic source of fluorine. These reactions take advantage of the beta effect of the silicon-carbon bond and recent results from the literature revealed that this chemistry allows for the preparation of a variety of novel fluorinated building blocks including enantio-enriched derivatives.

Alkenes↗
PubMed2005

Palladium-catalyzed oxidative cyclizations: synthesis of dihydropyranones and furanones.

A boron-mediated syn- and anti-stereoselective aldol reaction giving rise to various beta-hydroxyenones was coupled to a Pd((II))-mediated oxidative cyclization to give 2,3,6-trisubstituted syn- and anti-dihydropyranones in good yields. The Pd((II))-mediated oxidative cyclization was expanded to alpha-hydroxyenones leading to furan-3(2H)-one derivatives, which include natural product bullatenone and a known precursor of geiparvarin. The sole product of the oxidative cyclization of alpha,beta-dihydroxyenone was a five-membered furan-3(2H)-one derivative, suggesting that the ring closure of these diols is both chemo- and regioselective.

Journal Article↗
PubMed2005

Biocatalytic approaches to hetero-Diels-Alder adducts of carbonyl compounds.

Very little information is available on hetero-Diels-Alderases for the assembly of heterocyclic products despite the synthetic value of these [4+2] cycloadditions. Hetero-Diels-Alderase antibodies raised against a bicyclic transition state analogue have been generated for the cycloaddition of ethylglyoxylate with an all-carbon diene. More recently, a conceptually novel biocatalytic approach to hetero-Diels-Alder (HDA) adducts derived from carbonyl dienophiles has been developed mirroring a stepwise aldol Michael mechanism instead of a concerted pathway. In this approach, the two key steps are an antibody-mediated kinetic resolution of beta-hydroxyenones and a subsequent ring-closure process. An attractive feature of this methodology is the possibility to convert the enantioenriched aldol intermediates into tetrahydropyranones or dihydropyranones. This bioorganic route is best applied for the preparation of enantioenriched HDA adducts derived from poorly electrophilic acceptors, therefore complementing existing catalytic routes to these adducts based on the use of small organocatalysts or chiral Lewis acids.

Catalysis↗
PubMed2005

Synthesis of novel enantiopure fluorinated building blocks from acyclic chiral allylsilanes.

[reaction: see text] Homochiral beta-fluorinated gamma,delta-unsaturated carboxylic acids with an allylic fluorinated stereogenic center are available from the corresponding enantiopure allylsilanes. The key step for introduction of the fluorine substituent is an electrophilic fluorodesilylation reaction carried out in the presence of Selectfluor. Reduction of the resulting beta-fluorinated pentenoic acid into the corresponding fluorinated alcohol was also performed leading to the formation of an enantiopure second-generation fluorinated building block.

Journal Article↗
PubMed2005

A catalytic asymmetric bioorganic route to enantioenriched tetrahydro- and dihydropyranones.

A conceptually novel approach to hetero Diels-Alder adducts of carbonyl compounds is described using as the key steps an antibody-mediated kinetic resolution of hydroxyenones followed by a ring-closure process. Various beta-hydroxyenones proved to be very good substrates for antibodies 84G3- and 93F3-catalyzed retro-aldol reactions, allowing the preparation of highly enantiomerically enriched (up to 99% ee) precursors of pyranones. An attractive feature of this methodology is the possibility to convert these acyclic-enantioenriched beta-hydroxyenones into tetrahydropyranones by a conventional Michael-type addition procedure or into the corresponding dihydropyranones using an alternative palladium-catalyzed oxidative ring closure. For the palladium-mediated cyclization, a biphasic system has been implemented that allows the direct preparation of enantiopure dihydropyranones from the corresponding racemic aldol precursors using a sequential antibody-resolution/palladium-cyclization strategy, without isolation of the intermediate enantioenriched hydroxyenones. This bioorganic route is best applied to the preparation of hetero Diels-Alder adducts otherwise derived from less nucleophilic dienes and unactivated dienophiles.

Journal Article↗
PubMed2004

Oxidative cyclization of beta-hydroxyenones with palladium(II): a novel entry to 2,3-dihydro-4H-pyran-4-ones.

[reaction: see text] A palladium(II)-mediated oxidative cyclization was found to be effective for the preparation of structurally diverse 2,3-dihydro-4H-pyran-4-ones from the corresponding beta-hydroxyenones. Attractive features of this transformation include the ready availability of the starting enones, the regiocontrol, and the easy access of enantiopure 2,3-dihydro-4H-pyran-4-one from the corresponding enantiopure enone.

Journal Article↗