Diverse secondary C(sp<sup>3</sup>)–H bond functionalization <i>via</i> site-selective trifluoroacetoxylation of aliphatic amines

Tang, Yongzhen; Qin, Yuman; Meng, Dongmei; Li, Chaoqun; Wei, Junfa; Yang, Mingyu

doi:10.1039/c8sc01788c

Cited by 31 publications

(14 citation statements)

References 66 publications

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“…The remote C–H functionalization of amines via intramolecular hydrogen atom transfer (HAT) has enabled a distinct approach to the synthesis of pyrrolidines for over a century 1,2. Yet, while this formal δ C–H amination has been interrupted to afford distal halogenation and oxygenation, it has rarely enabled δ C–C bond formation 3–5. A mechanistic explanation is that initiation of this radical rearrangement requires homolysis of an N-halo amide to generate the N-centered radical (Fig.…”

Section: Introductionmentioning

confidence: 99%

δ C–H (hetero)arylationviaCu-catalyzed radical relay

2019

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Section: Introductionmentioning

confidence: 99%

δ C–H (hetero)arylationviaCu-catalyzed radical relay

2019

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“…Due to the synthetic utility of the trifluoroacetoxyl group, [32] Yang et al described the direct remote trifluoroacetoxylation reaction of aliphatic N-protected benzoyl amines at the -position mediated by an amidyl radical. [33] The use of a catalytic amount of copper iodide and tetrabutylammonium bromide in presence of the bis((trifluoroacetoxy)iodo)benzene and bromine to form the intermediate radical, allowed the synthesis of the desired -trifluoroacetoxylated benzoylamides (Scheme 14, 31 examples, up to 82% yield). Aliphatic benzoylamides having various carbon chain lengths (38a-c) were functionalized with a full selectivity towards the -position.…”

Section: Trifluoroacetoxylation Reactionsmentioning

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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“… Selective trifluoroacetoxylation of aliphatic N ‐protected benzoylamines via a 1,5‐HAT [33] . [a] 8 h of reaction.…”

Section: Distal Functionalization Via 15‐hydrogen Atom Transfermentioning

confidence: 99%

“…Due to the synthetic utility of the trifluoroacetoxyl group, [32] Yang et al. described the direct remote trifluoroacetoxylation reaction of aliphatic N ‐protected benzoyl amines at the δ‐position mediated by an amidyl radical [33] . The use of a catalytic amount of copper iodide and tetrabutylammonium bromide in the presence of the bis((trifluoroacetoxy)iodo)benzene and bromine to form the intermediate radical allowed the synthesis of the desired δ‐trifluoroacetoxylated benzoylamides (Scheme 14, 31 examples, up to 82 % yield).…”

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 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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Diverse secondary C(sp³)–H bond functionalization via site-selective trifluoroacetoxylation of aliphatic amines

Abstract: A coinage-metal-catalyzed site-selective trifluoroacetoxylation of remote secondary C(sp3)–H bonds for aliphatic amine substrates was developed.

Cited by 31 publications

References 66 publications

δ C–H (hetero)arylationviaCu-catalyzed radical relay

δ C–H (hetero)arylationviaCu-catalyzed radical relay

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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Diverse secondary C(sp3)–H bond functionalization via site-selective trifluoroacetoxylation of aliphatic amines

Abstract: A coinage-metal-catalyzed site-selective trifluoroacetoxylation of remote secondary C(sp3)–H bonds for aliphatic amine substrates was developed.

Cited by 31 publications

References 66 publications

δ C–H (hetero)arylationviaCu-catalyzed radical relay

δ C–H (hetero)arylationviaCu-catalyzed radical relay

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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Product

Resources

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Diverse secondary C(sp³)–H bond functionalization via site-selective trifluoroacetoxylation of aliphatic amines

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