Fluorine &amp; chirality: how to create a nonracemic stereogenic carbon–fluorine centre?

Cahard, Dominique; Xu, Xiu‐Hua; Couve‐Bonnaire, Samuel; Pannecoucke, Xavier

doi:10.1039/b909566g

Cited by 225 publications

(53 citation statements)

References 40 publications

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“…[35][36][37][38] Recently, catalytic fluorinations inclusive of asymmetric variants were developed using electrophilic fluorine sources. Electronrich p-systems such as metal enolates, 39 enamines, [40][41][42] various organosilanes [43][44][45] and indoles 46 have been investigated in this context.…”

Section: C(sp 3 )-F Bond Constructionmentioning

confidence: 99%

Transition metal catalysis and nucleophilic fluorination

2012

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Transition metal catalyzed transformations using fluorinating reagents have been developed extensively for the preparation of synthetically valuable fluorinated targets. This is a topic of critical importance to facilitate laboratory and industrial chemical synthesis of fluorine containing pharmaceuticals and agrochemicals. Translation to (18)F-radiochemistry is also emerging as a vibrant research field because functional imaging based on Positron Emission Tomography (PET) is increasingly used for both diagnosis and pharmaceutical development. This review summarizes how fluoride sources have been used for the catalytic nucleophilic fluorination of various substrates inclusive of aryl triflates, alkynes, allylic halides, allylic esters, allylic trichloroacetimidates, benzylic halides, tertiary alkyl halides and epoxides. Until recently, progress in this field of research has been slow in part because of the challenges associated with the dual reactivity profile of fluoride (nucleophile or base). Despite these difficulties, some remarkable breakthroughs have emerged. This includes the demonstration that Pd(0)/Pd(II)-catalyzed nucleophilic fluorination to access fluoroarenes from aryl triflates is feasible, and the first examples of Tsuji-Trost allylic alkylation with fluoride using either allyl chlorides or allyl precursors bearing O-leaving groups. More recently, allylic fluorides were also made accessible under iridium catalysis. Another reaction, which has been greatly improved based on careful mechanistic work, is the catalytic asymmetric hydrofluorination of meso epoxides. Notably, each individual transition metal catalyzed nucleophilic fluorination reported to date employs a different F-reagent, an observation indicating that this area of research will benefit from a larger pool of nucleophilic fluoride sources. In this context, a striking recent development is the successful design, synthesis and applications of a fluoride-derived electrophilic late stage fluorination reagent. This new class of reagents could greatly benefit preclinical and clinical PET imaging.

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Section: C(sp 3 )-F Bond Constructionmentioning

confidence: 99%

Transition metal catalysis and nucleophilic fluorination

2012

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“…[3] The interest in chiral fluorinated compounds is not new but has increased in recent years. [4,5] Apart from their use in asymmetric synthesis, some fluorinated organic compounds exhibit peculiar and sometimes unexpected chiroptical properties, which have been discussed and rationalized. [6][7][8][9][10][11] The second context mentioned above is crystal engineering, for which the characteristic noncovalent inter-transfer (CT) character, as demonstrated by the CT metric index Γ NTO .…”

Section: Introductionmentioning

confidence: 99%

Circular Dichroism and TDDFT Investigation of Chiral Fluorinated Aryl Benzyl Sulfoxides

et al. 2015

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A series of ten chiral aryl benzyl sulfoxides with perfluorinated aryl or benzyl rings, obtained by enantioselective oxidation of sulfides, has been investigated by means of electronic circular dichroism (ECD) spectroscopy and time-dependent DFT (TDDFT) calculations. The (per)fluorination of the aromatic rings has a large impact on the conformer population, the molecular orbitals shape, and the character of electronic transitions. In this series, the transition responsible for the “sulfoxide primary” CD band has a large charge transfer (CT) character, as demonstrated by the CT metric index ΓNTO. As a consequence, global DFT hybrids such as B3LYP are largely inaccurate in the prediction of excited states; nevertheless, a correct simulation of CD spectra may be achieved by using range-separated functionals such as CAM-B3LYP. The use of the empirical Mislow's rule for assigning the absolute configuration is strongly discouraged for this class of compounds

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“…Selective introduction of the fluorine atom(s) or fluorinecontaining moieties into organic compounds to modulate their biological properties has become a routine and powerful strategy in both drug design and agrochemical development [1][2][3][4][5][6][7][8][9][10][11][12]. In this context, -alkyl or -alkenyl ,-difluorinated sulfonamides have recently drawn much attention, since the introduction of two fluorine atoms into the carbon atom  to the sulfonamide functionality results in a decrease of the basicity of sulfonamide as well as an increase of lipophilicity [13].…”

Section: Introductionmentioning

confidence: 99%