1,2-Radical Shifts in Photoinduced Synthetic Organic Transformations: A Guide to the Reactivity of Useful Radical Synthons

Matsuo, Bianca; Granados, Albert; Majhi, Jadab; Sharique, Mohammed; Levitre, Guillaume; Molander, Gary A.

doi:10.1021/acsorginorgau.2c00032

Cited by 20 publications

(25 citation statements)

References 82 publications

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“…Thus, the formate radical anion is unlikely to be contributing to the reduction of 2. 30,33,36,57 From this point, the formed C-centered radical anion species Ac − undergoes a spin-center shi (SCS) 58 to form the electrophilic gem-diuoromethyl radical intermediate Cc, which was also observed as a TEMPO adduct in the control experiments. DFT computations suggest that the SCS proceeds through a stepwise 1,2-F migration pathway (TS-A-B), wherein the uorine on the terminal carbon shis to the carbonyl carbon.…”

Section: Discussionmentioning

confidence: 96%

Transition metal-free photochemical C–F activation for the preparation of difluorinated-oxindole derivatives

et al. 2023

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Section: Discussionmentioning

confidence: 96%

Transition metal-free photochemical C–F activation for the preparation of difluorinated-oxindole derivatives

et al. 2023

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“…32 The thiolate can be photoexcited with light to generate the photoexcited thiolate species (B). 32 Species B reduces 2a, generating C and D. 32 Radical C undergoes a spin-centered shift (SCS), 31,40 generating difluoroalkyl radical E (which was trapped by TEMPO as shown in Scheme 4B), which adds to the indole substrate, generating F. At this point, the thiyl radical D undergoes single electron transfer (SET) with F, regenerating thiolate A and cation G resulting from a radical/polar crossover. Deprotonation with the base then furnishes the product 4.…”

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Visible-Light-Induced C–F Bond Activation for the Difluoroalkylation of Indoles

et al. 2022

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An aryl disulfide mediated C−F bond activation of the trifluoromethyl group to generate valuable gem-difluoroalkylindoles is described. This method relies on readily available commodity reagents under mild reaction conditions and represents the first transition-metal-free redox-neutral C−F bond activation strategy. The reaction employs various substituted indoles and αfluoro-substituted esters. Further, this mode of C−F activation was also amenable to the activation of trifluoromethylated arenes for the preparation of bis-benzylic gem-difluoromethylenes between indole and arene substructures, providing access to a unique chemical space.T he incorporation of fluorine into organic molecules is well-known to alter chemical properties, including stability, reactivity, acidity, and conformational bias. 1−3 Therefore, substantial efforts have been invested in incorporating these motifs into organic frameworks. 1,2,4,5 For example, over 50% of new agrochemicals introduced on the market from 1998 to 2020 contained at least one C−F bond, 6 and over 40% of new small molecule drugs in 2018 and 2019 were fluorinated compounds. 7 Another important class of pharmaceutically relevant motifs are indoles, 8,9 as they are among the most prevalent substructures in biologically active small-molecule drugs. 10,11 Consequently, the ability to incorporate fluorine onto indoles is of high interest and has been pursued in both academic and industrial laboratories. 12 Specifically, the gem-difluoromethylene motif is an attractive bioisostere for common organic functional groups such as alcohols, amines, and ketones, and is known to improve biological properties while providing greater chemical stability. 13,14 Early efforts on the synthesis of gem-difluoromethylated indoles relied on the use of transition-metal-mediated or -catalyzed reactions (Scheme 1A). These methods require the use of catalytic Pd, 15 Ni, 16 or Cu 17,18 under elevated temperatures. Further, these methods make use of either the activated ethyl (iodo-or bromo)difluoroacetate precursor. Another report of a Rh-catalyzed method exists. 19 However, this approach requires the use of a difluorovinyl precursor at elevated temperatures. More recently, light-induced methods for the preparation of difluoromethylene-containing indoles have appeared in the literature as an alternative (Scheme 1B). These methods used an iridium, 20,21 ruthenium, 22,23 or a triphenylphosphine photocatalyst. 24 However, these lightinduced methods again relied on the use of activated, noncommodity reagents, and do not provide access to a large pool of available substrates. Thus, the ability to install the gem-difluoroalkyl group onto indoles with a more diverse

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“…The development of new synthetic reactions using known organic or inorganic photocatalysts is also included in this issue. Gary Molander et al present recent advances in photoinduced chemical reactions involving 1,2-radical shifts . This Review provides an excellent overview of the recent synthetic applications of this radical process, with special emphasis on understanding the mechanism and its utility for the synthesis of organic molecules.…”

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confidence: 99%

“…This Review provides an excellent overview of the recent synthetic applications of this radical process, with special emphasis on understanding the mechanism and its utility for the synthesis of organic molecules. Then, Maurizio Fagnoni et al describe recent progress in visible-light-promoted selenylation, presenting useful radical methodologies for C(sp 2 )–Se bond and C(sp 3 )–Se bond formation . The authors also highlight the need to develop new photocatalytic synthetic procedures to form (sp 3 )–Se bonds.…”

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confidence: 99%

“…Gary Molander et al present recent advances in photoinduced chemical reactions involving 1,2-radical shifts. 17 This Review provides an excellent overview of the recent synthetic applications of this radical process, with special emphasis on understanding the mechanism and its utility for the synthesis of organic molecules. Then, Maurizio Fagnoni et al describe recent progress in visible-light-promoted selenylation, presenting useful radical methodologies for C(sp 2 )–Se bond and C(sp 3 )–Se bond formation.…”

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confidence: 99%

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