Carbon Trifluoromethylation Reactions of Hydrocarbon Derivatives and Heteroarenes

Alonso, C.; Marigorta, Eduardo Martı́nez de; Rubiales, Gloria; Palacios, Francisco

doi:10.1021/cr500368h

Cited by 957 publications

(348 citation statements)

References 488 publications

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“…36 A number of methods have proven effective on the discovery scale, though these typically employ specialized reagents 37 with weakened X–CF 3 bonds to facilitate in situ generation of the operative trifluoromethylation intermediate. In hopes of providing an approach tailored to industrial scales, our design focused on using abundantly available CF 3 sources and eliminating the need for prefunctionalized substrates.…”

Section: Targeting Pharmaceutically Relevant Scaffoldsmentioning

confidence: 99%

Free Radical Chemistry Enabled by Visible Light-Induced Electron Transfer

2016

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ConspectusHarnessing visible light as the driving force for chemical transformations generally offers a more environmentally friendly alternative compared with classical synthetic methodology. The transition metal-based photocatalysts commonly employed in photoredox catalysis absorb efficiently in the visible spectrum, unlike most organic substrates, allowing for orthogonal excitation. The subsequent excited states are both more reducing and more oxidizing than the ground state catalyst and are competitive with some of the more powerful single-electron oxidants or reductants available to organic chemists yet are simply accessed via irradiation. The benefits of this strategy have proven particularly useful in radical chemistry, a field that traditionally employs rather toxic and hazardous reagents to generate the desired intermediates.In this Account, we discuss our efforts to leverage visible light photoredox catalysis in radical-based bond-forming and bond-cleaving events for which few, if any, environmentally benign alternatives exist. Mechanistic investigations have driven our contributions in this field, for both facilitating desired transformations and offering new, unexpected opportunities. In fact, our total synthesis of (+)-gliocladin C was only possible upon elucidating the propensity for various trialkylamine additives to elicit a dual behavior as both a reductive quencher and a H-atom donor. Importantly, while natural product synthesis was central to our initial motivations to explore these photochemical processes, we have since demonstrated applicability within other subfields of chemistry, and our evaluation of flow technologies demonstrates the potential to translate these results from the bench to pilot scale.Our forays into photoredox catalysis began with fundamental methodology, providing a tin-free reductive dehalogenation that exchanged the gamut of hazardous reagents previously employed for such a transformation for visible light-mediated, ambient temperature conditions. Evolving from this work, a new avenue toward atom transfer radical addition (ATRA) chemistry was developed, enabling dual functionalization of both double and triple bonds. Importantly, we have also expanded our portfolio to target clinically relevant scaffolds. Photoredox catalysis proved effective in generating high value fluorinated alkyl radicals through the use of abundantly available starting materials, providing access to libraries of trifluoromethylated (hetero)arenes as well as intriguing gem-difluoro benzyl motifs via a novel photochemical radical Smiles rearrangement. Finally, we discuss a photochemical strategy toward sustainable lignin processing through selective C–O bond cleavage methodology. The collection of these efforts is meant to highlight the potential for visible light-mediated radical chemistry to impact a variety of industrial sectors.

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Section: Targeting Pharmaceutically Relevant Scaffoldsmentioning

confidence: 99%

Free Radical Chemistry Enabled by Visible Light-Induced Electron Transfer

2016

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“…Thanks to data obtained from DFT calculations it was possible to better understand the mechanical aspects of the synthesis of perfluoralkylfunctionalized five-membered heterocycles with potential biological activity [11,12].…”

Section: Page 5 Of 17mentioning

confidence: 99%

On the question of zwitterionic intermediates in 1,3-dipolar cycloadditions between hexafluoroacetone and sterically crowded diazocompounds

Jasiński

2015

Journal of Fluorine Chemistry

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“…1−4 During the past decades, an increasing attention has been paid to the trifluoromethylation of arenes and heteroarenes, which are fundamental building blocks of many top-selling pharmaceuticals and agrochemicals, including celecoxib, cinacalcet, nilotinib, beflubutamid, norfluazon, and so on. 5 However, the traditional cross-coupling methodologies usually require stoichiometric amounts of metal complexes, preactivated substrates, or directing groups. 6 Substrate scope also suffers from severe limitations due to the harsh reaction conditions.…”

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confidence: 99%

Simple and Clean Photoinduced Aromatic Trifluoromethylation Reaction

et al. 2016

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We describe a simple, metal-and oxidantfree photochemical strategy for the direct trifluoromethylation of unactivated arenes and heteroarenes under either ultraviolet or visible light irradiation. We demonstrated that photoexcited aliphatic ketones, such as acetone and diacetyl, can be used as promising low-cost radical initiators to generate CF 3 radicals from sodium triflinate efficiently. The broad utility of this strategy and its benefit to medicinal chemistry are demonstrated by the direct trifluoromethylation of unprotected bidentate chelating ligand, xanthine alkaloids, nucleosides, and related antiviral drug molecules.

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Carbon Trifluoromethylation Reactions of Hydrocarbon Derivatives and Heteroarenes

Cited by 957 publications

References 488 publications

Free Radical Chemistry Enabled by Visible Light-Induced Electron Transfer

Free Radical Chemistry Enabled by Visible Light-Induced Electron Transfer

On the question of zwitterionic intermediates in 1,3-dipolar cycloadditions between hexafluoroacetone and sterically crowded diazocompounds

Simple and Clean Photoinduced Aromatic Trifluoromethylation Reaction

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