PIFA-Promoted, Solvent-Controlled Selective Functionalization of C(sp2)–H or C(sp3)–H: Nitration via C–N Bond Cleavage of CH3NO2, Cyanation, or Oxygenation in Water

Mudithanapelli, Chandrashekar; Dhorma, Lama Prema; Kim, Mi‐Hyun

doi:10.1021/acs.orglett.9b00751

Cited by 32 publications

(14 citation statements)

References 69 publications

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“…The resulting fluorinated intermediate is prone to hydrolysis under acidic conditions to give hemiaminal. This approach is advantageous over direct hydroxylation using OH radical, as hyperconjugative activation of hemiaminals often leads to over-oxidation to the carbonyl [43][44][45] .…”

Section: Resultsmentioning

confidence: 99%

Copper catalyzed late-stage C(sp3)-H functionalization of nitrogen heterocycles

et al. 2021

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Nitrogen heterocycle represents a ubiquitous skeleton in natural products and drugs. Late-stage C(sp3)-H bond functionalization of N-heterocycles with broad substrate scope remains a challenge and of particular significance to modern chemical synthesis and pharmaceutical chemistry. Here, we demonstrate copper-catalysed late-stage C(sp3)-H functionalizaion of N-heterocycles using commercially available catalysts under mild reaction conditions. We have investigated 8 types of N-heterocycles which are usually found as medicinally important skeletons. The scope and utility of this approach are demonstrated by late-stage C(sp3)-H modification of these heterocycles including a number of pharmaceuticals with a broad range of nucleophiles, e.g. methylation, arylation, azidination, mono-deuteration and glycoconjugation etc. Preliminary mechanistic studies reveal that the reaction undergoes a C-H fluorination process which is followed by a nucleophilic substitution.

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Section: Resultsmentioning

confidence: 99%

Copper catalyzed late-stage C(sp3)-H functionalization of nitrogen heterocycles

et al. 2021

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“…A base (e.g., K 2 CO 3 ) was essential to prevent acid catalytic decomposition of the intermediate in general conditions. According to our recent study on the solvent effect of C-H functionalization of trivalent iodine 7,8 , nitromethane presented consistently the product of 60% isolated yield without any base. After improving the cost-effectiveness and synthetic efficiency of the reaction, aromatic azides 8a-r were synthesized according to the literature protocol 46 .…”

Section: Resultsmentioning

confidence: 90%

Positioning of an unprecedented spiro[5.5]undeca ring system into kinase inhibitor space

Venkanna

Subedi

Teli

et al. 2020

Sci Rep

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In-house 1,5-oxaza spiroquinone 1, with spiro[5.5]undeca ring system, was announced as an unprecedented anti-inflammatory scaffold through chemistry-oriented synthesis (ChOS), a chemocentric approach. Herein, we studied how to best position the spiro[5.5]undeca ring system in kinase inhibitor space. Notably, late-stage modification of the scaffold 1 into compounds 2a-r enhanced kinase-likeness of the scaffold 1. The improvement could be depicted with (1) selectivity with target shift (from JNK-1 into GSK-3) and (2) potency (> 20-fold). In addition, ATP independent IC50 of compound 2j suggested a unique binding mode of this scaffold between ATP site and substrate site, which was explained by docking based optimal site selection and molecular dynamic simulations of the optimal binding site. Despite the shift of kinase profiling, the anti-inflammatory activity of compounds 2a-r could be retained in hyperactivated microglial cells.

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“…In 2019, the Kim group reported a metal-free PIFA-promoted nitration of arylamines mediated by nitromethane (Scheme 38). 79 The reaction demonstrated excellent compatibility with various functional groups. However, the scope of this method was limited to arylamines 152 and could not be extended to phenols and derivatives.…”

Section: Nitroalkanesmentioning

confidence: 94%

Organic Nitrating Reagents

Patra¹,

Mosiagin²,

Katayev³

et al. 2022

Synthesis

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Nitro compounds are vital raw chemicals that are widely used in academic laboratories and industries for the preparation of various drugs, agrochemicals, and materials. Thus, nitrating reactions are of great importance for chemists and are even taught in schools as one of the fundamental transformations in organic synthesis. Since the discovery of the first nitrating reactions in the 19th century, progress in this field has been constant. Yet, for many years the classical electrophilic nitration approach using a mixture of strong mineral acids dominated the field. However, in recent decades, the attention of researchers has focused on new reactivity and new reagents that can provide access to nitro compounds in a practical and straightforward way under mild reaction conditions. Organic nitrating reagents have played a special role in this field since they have enhanced reactivity. They also allow nitration to be carried out in an ecofriendly and sustainable manner. This review examines the development and application of organic nitrating reagents.1 Introduction2 Organic Nitrating Reagents2.1 Alkyl Nitrites2.2 Nitroalkanes2.3 Alkyl Nitrates2.4 N-Nitroamides2.5 N-Nitropyrazole2.6 N-Nitropyridinium Salts3 Organic Nitrating Reagents Generated In Situ3.1 Acyl Nitrates3.2 Trimethylsilyl Nitrate3.3 Nitro Onium Salts4 Organic Nitronium Salts5 Organic Nitrates and Nitrites5.1 Ammonium Nitrates5.2 Heteroarylium Nitrates5.3 Other Organic Nitrates5.4 Organic Nitrites6 Conclusion and Outlook

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PIFA-Promoted, Solvent-Controlled Selective Functionalization of C(sp²)–H or C(sp³)–H: Nitration via C–N Bond Cleavage of CH₃NO₂, Cyanation, or Oxygenation in Water

Cited by 32 publications

References 69 publications

Copper catalyzed late-stage C(sp3)-H functionalization of nitrogen heterocycles

Copper catalyzed late-stage C(sp3)-H functionalization of nitrogen heterocycles

Positioning of an unprecedented spiro[5.5]undeca ring system into kinase inhibitor space

Organic Nitrating Reagents

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