Iodine Catalysis for C(sp<sup>3</sup>)–H Fluorination with a Nucleophilic Fluorine Source

Bafaluy, Daniel; Georgieva, Zoritsa; Muñiz, Kilian

doi:10.1002/anie.202004902

Cited by 43 publications

(25 citation statements)

References 73 publications

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“…This, in turn, is promoted by excess amounts of the nucleophilic uoride source, HF$amine. 33 Indeed, treating the iodouorinated product 12ca with TolIF 2 and 5.6HF$amine yielded the diuorinated product 12cb. The pharmaceutically relevant compounds 12d and 13a were also synthesised in good yields, 12d through the iodo-uorination of the alkene and 13a by the electrochemical uorination of the corresponding thioacetal.…”

Section: Resultsmentioning

confidence: 99%

Flow electrochemistry: a safe tool for fluorine chemistry

2021

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Section: Resultsmentioning

confidence: 99%

Flow electrochemistry: a safe tool for fluorine chemistry

2021

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“…Very recently, it was demonstrated that a nucleophilic reagent might be used instead of an electrophilic one. In 2020, Bafaluy, Muñiz and co‐workers developed an iodine‐catalyzed fluorination of aliphatic sulfamides and sulfonamides with NEt 3 ⋅3 HF under light irradiation [16] . Kinetically favored by the particular geometry of sulfamides (elongated S−N bonds), [17] the functionalization of these derivatives occurred at the γ‐position through a 1,6‐HAT process, while in case of sulfonamide derivatives, the distal fluorination was selective to the δ‐position via a 1,5‐HAT process (Scheme 7).…”

Section: Distal Functionalization Via 15‐hydrogen Atom Transfermentioning

confidence: 99%

Radical‐Promoted Distal C−H Functionalization of C(sp³) Centers with Fluorinated Moieties

2021

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Due to their unique properties, fluorinated scaffolds are pivotal compounds in pharmaceuticals, agrochemicals and materials science. Over the last years, the development of versatile strategies for the selective synthesis of fluorinated molecules by direct C−H bond functionalization has attracted a lot of attention. In particular, the design of novel transformations based on a radical process was a bottleneck for the distal C−H functionalization reactions, offering synthetic solutions for the selective introduction of a fluorinated group. This Minireview highlights the major contributions that have been made in this blossoming field. The development of new methodologies for the remote functionalization of aliphatic derivatives with various fluorinated groups based on a 1,5-HAT process and a -fragmentation reaction will be mainly showcased and discussed.Scheme 3. Synthesis of -fluorinated ketone derivatives via an iminyl radical generated by a photoredox process. Acr + -Mes ClO4 -= 9-mesityl-10methylacridinium perchlorate. Boc = tert-butyloxycarbonyl.Aiming at developing a general approach, the same group showed that changing the nature of the nitrogen radical, from iminyl radicals to amidyl ones, the fluorination of remote tertiary, secondary and primary C−H bonds was possible (Scheme 4, 31 examples, up to 89% yield). [11] Using an Ir (III) catalyst, in the presence of Selectfluor along with cesium carbonate, an access to fluorinated amide derivatives at the -position was developed starting from the corresponding carboxylic acid precursors 3. The reaction proved to be efficient for the remote fluorination of tertiary (3a), secondary (3b), and primary (3c) C(sp 3 ) centers leading to the corresponding fluorinated N-methyl amides (4a-c). Note that the fluorination of a benzylic position was possible and the compound 4d was synthesized in a good yield. The transformation was not limited to the functionalization of N-methyl amides as the -fluorinated N-benzyl amide (4e) or the primary amide (4f) were successfully obtained. This distal fluorination was efficient on amides containing cycloalkyls (3g-i), offering an access to potentially interesting bioactive building blocks such as a N-Boc-piperidine (4i). The methodology was extended to the selective latestage remote fluorination of protected-amino acid derivatives (3j and 3k) and the dipeptide building block 3l. Furthermore, the transformation was not restricted to amide derivatives as the synthesis of fluorinated carbamate (4m) and N-protected amines (4n-p) at the -and -positions, respectively, was also possible. When the amide (3q) or the carbamate (3r) bearing a competitive tertiary center at the -position was used, the fluorination at this position was preferentially achieved via a 1,6-HAT process. [12] However, in case of the N-Boc-protected amine 3s, a mixture of fluorinated products (4s and 4s') at the -and -positions was obtained in a 1:1 ratio, presumably due to a higher chain flexibility. The following mechanism was suggested: under basic conditi...

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“… Remote fluorination of C(sp 3 )‐H centers with fluoride [16] . Ar=3‐ClC 6 H 4 .…”

Section: Distal Functionalization Via 15‐hydrogen Atom Transfermentioning

confidence: 99%

Radical‐Promoted Distal C−H Functionalization of C(sp³) Centers with Fluorinated Moieties

2021

View full text Add to dashboard Cite

Due to their unique properties, fluorinated scaffolds are pivotal compounds in pharmaceuticals, agrochemicals, and materials science. Over the last years, the development of versatile strategies for the selective synthesis of fluorinated molecules by direct C−H bond functionalization has attracted a lot of attention. In particular, the design of novel transformations based on a radical process was a bottleneck for distal C−H functionalization reactions, offering synthetic solutions for the selective introduction of fluorinated groups. This Minireview highlights the major contributions in this blossoming field. The development of new methodologies for the remote functionalization of aliphatic derivatives with various fluorinated groups based on a 1,5‐hydrogen atom transfer process and a β‐fragmentation reaction will be showcased and discussed.

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Iodine Catalysis for C(sp³)–H Fluorination with a Nucleophilic Fluorine Source

Cited by 43 publications

References 73 publications

Flow electrochemistry: a safe tool for fluorine chemistry

Flow electrochemistry: a safe tool for fluorine chemistry

Radical‐Promoted Distal C−H Functionalization of C(sp³) Centers with Fluorinated Moieties

Radical‐Promoted Distal C−H Functionalization of C(sp³) Centers with Fluorinated Moieties

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Iodine Catalysis for C(sp3)–H Fluorination with a Nucleophilic Fluorine Source

Cited by 43 publications

References 73 publications

Flow electrochemistry: a safe tool for fluorine chemistry

Flow electrochemistry: a safe tool for fluorine chemistry

Radical‐Promoted Distal C−H Functionalization of C(sp3) Centers with Fluorinated Moieties

Radical‐Promoted Distal C−H Functionalization of C(sp3) Centers with Fluorinated Moieties

Contact Info

Product

Resources

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Iodine Catalysis for C(sp³)–H Fluorination with a Nucleophilic Fluorine Source

Radical‐Promoted Distal C−H Functionalization of C(sp³) Centers with Fluorinated Moieties

Radical‐Promoted Distal C−H Functionalization of C(sp³) Centers with Fluorinated Moieties