Divergent Synthesis of α-Aroyloxy Ketones and Indenones: A Controlled Domino Radical Reaction for Di- and Trifunctionalization of Alkynes

Jafarpour, Farnaz; Azizzade, Meysam; Golpazir-Sorkheh, Yekta; Navid, Hamed; Rajai‐Daryasarei, Saideh

doi:10.1021/acs.joc.0c00967

“…This broad substrate scope is remarkable, as comparable reaction conditions for the α-C–H cyanation of tertiary amines frequently employ peroxide-based oxidants (e.g., t BuOOH). Such oxidants typically lead to free radicals as reaction intermediates, − which can attack olefinic, alkyne, , and heterocyclic substructures of complex amine substrates and are thus fundamentally limited in their scope. The presented work circumvents this issue by designing an Fe-based catalyst system that potentially relies on a radical-rebound mechanism.…”

Section: Resultsmentioning

confidence: 99%

Iron-Catalyzed α-C–H Cyanation of Simple and Complex Tertiary Amines

Yılmaz

¹

,

Dengiz

²

,

Emmert

³

2021

J. Org. Chem.

4

0

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This manuscript details the development of a general and mild protocol for the α-C-H cyanation of tertiary amines as well as its application in late stage functionalization. Suitable substrates include tertiary aliphatic, benzylic, and aniline-type substrates as well as complex substrates. Functional groups tolerated under the reaction conditions include various heterocycles, as well as ketones, amides, olefins, and alkynes. This broad substrate scope is remarkable, as comparable reaction protocols for α-C-H cyanation frequently occur via free radical mechanisms, and are thus fundamentally limited in their functional group tolerance. In contrast, the presented catalyst system tolerates functional groups that typically react with free radicals, suggesting an alternative reaction pathway. All components of the described system are readily available, allowing implementation of the presented methodology without the need for lengthy catalyst synthesis.Recent mechanistic work in the Fe catalyzed α-C-H oxidation of tertiary amines has uncovered a radical rebound ASSOCIATED CONTENT Supporting Information. Reaction optimization details, synthetic procedures, characterization for new and known compounds.

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“…4, 155.1, 145.9, 144.6, 133.1, 133.0, 131.1, 130.2, 129.3, 129.1, 129.0, 128.7, 128.6, 128.2, 127.8, 123.2, 122.7, 22.3; 1 H NMR (400 MHz, CDCl 3 ) δ: 7.47 (d,J＝7.3 Hz,1H),7.44～7.34 (m,5H),7.24 (d,J＝6.1 Hz,5H),7.07 (d,J＝ 7.3 Hz,1H),6.93 (s,1H), 2.34 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ: 196. 4, 155.1, 145.9, 144.6, 133.0, 133.0, 131.0, 130.1, 129.3, 129.1, 129.0, 128.7, 128.5, 128.2, 127.8, 123.2, 122.7, 22.3. 5-Fluoro-2,3-diphenyl-1H-inden-1-one (3e): [20] Eluent: petroleum ether/ethyl acetate (V∶V＝200∶1), red oil, yield 70% (21.0 mg). 1 H NMR (400 MHz, CDCl 3 ) δ: 7.57 (dd,J＝7.9,5.2 Hz,1H),7.45～7.33 (m,5H),7.26 (d,J＝ 2.3 Hz,5H),6.93 (ddd,J＝8.9,8.0,2.2 Hz,1H),6.87 (dd,J＝8.5,2.1 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ: 195.0, 166.7 (d,J＝254.2 Hz),153.3 (d,J＝2.3 Hz),148.8 (d,J＝9.4 Hz),133.9,132.4,130.6,130.2,129.7,129.2,128.6,128.3,128.2,…”

Section: Characterization Of the Productmentioning

confidence: 99%

UV-Light-Initiated Construction of Indenones through Cyclization of Aryl Aldehydes or Aryl Ketones with Alkynes Avoiding Photocatalyst

Xiao¹,

Yang²,

Zhang³

et al. 2021

Chinese Journal of Organic Chemistry

3

0

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The first UV-light-initiated cyclization of aryl aldehydes or aryl ketones with alkynes has been developed for the preparation of indenones. This reaction could proceed smoothly under UV-light with O2 as an oxidant and photocatalyst-free condition, which features high efficiency, high atom economy, easily available starting materials, environmental friendliness, and tolerance to broad functional groups.

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“…This broad substrate scope is remarkable, as comparable reaction conditions for the α-C-H cyanation of tertiary amines frequently employ peroxide-based oxidants (e.g., t BuOOH). Such oxidants typically lead free radicals as reaction intermediates, [35][36][37] which can attack olefinic, 38 alkyne, 39,40 and heterocyclic 41 substructures of complex amine substrates and are thus fundamentally limited in their scope. The presented work circumvents this issue by designing an Fe-based catalyst system that potentially relies on substrate binding and a radical-rebound mechanism.…”

Section: Scheme 6 Mechanistic Hypothesis For Fe Catalyzedmentioning

confidence: 99%

Iron Catalyzed α-C-H Cyanation of Simple and Complex Tertiary Amines

Yılmaz¹,

Dengiz²,

Emmert

³

2020

Preprint

View full text Add to dashboard Cite

This manuscript details the development of a general and mild protocol for the α-C-H cyanation of tertiary amines as well as its application in late stage functionalization. Suitable substrates include tertiary aliphatic, benzylic, and aniline-type substrates as well as complex substrates. Functional groups tolerated under the reaction conditions include various heterocycles, as well as ketones, amides, olefins, and alkynes. This broad substrate scope is remarkable, as comparable reaction protocols for α-C-H cyanation frequently occur via free radical mechanisms, and are thus fundamentally limited in their functional group tolerance. In contrast, the presented catalyst system tolerates functional groups that typically react with free radicals, suggesting an alternative reaction pathway. All components of the described system are readily available, allowing implementation of the presented methodology without the need for lengthy catalyst synthesis.

show abstract

Divergent Synthesis of α-Aroyloxy Ketones and Indenones: A Controlled Domino Radical Reaction for Di- and Trifunctionalization of Alkynes

Cited by 16 publications

References 82 publications

Iron-Catalyzed α-C–H Cyanation of Simple and Complex Tertiary Amines

Iron-Catalyzed α-C–H Cyanation of Simple and Complex Tertiary Amines

UV-Light-Initiated Construction of Indenones through Cyclization of Aryl Aldehydes or Aryl Ketones with Alkynes Avoiding Photocatalyst

Iron Catalyzed α-C-H Cyanation of Simple and Complex Tertiary Amines

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